Advanced Solid TumorsPhase 1/2NCT02460224
Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.
A Phase 1/2 study testing LAG525 and PDR001 in people with Advanced Solid Tumors, run by Novartis Pharmaceuticals at 24 sites in 12 countries.
Trial summary
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- LAG525 and PDR001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 490 participants
- Where
- 24 sitesin 12 countries
- Study dates
- 17 Jun 2015to 31 Dec 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase I part:
- Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists
- Phase II part:
- Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have had disease progression following their last prior therapy and fit into one of the following groups:
- Group 1: NSCLC
- Group 2: Melanoma
Show all 11Show fewer
- Group 3: Renal cancer
- Group 4: Mesothelioma
- Group 5: TNBC
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy.
Who cannot join
- History of severe hypersensitivity reactions to study treatment ingredients or other mAbs
- Active, known or suspected autoimmune disease
- Active infection requiring systemic antibiotic therapy
- HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Patients receiving chronic treatment with systemic steroid therapy, other than replacement-dose corticosteroids in the setting of adrenal insufficiency
- Patients receiving systemic treatment with any immunosuppressive medication
Show all 10Show fewer
- Use of live vaccines against infectious disease within 4 weeks of initiation of study treatment
- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.
- Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy or increasing doses of corticosteroids within the prior 2 weeks
- History of drug-induced pneumonitis or current pneumonitis.
Trial locations and contacts
24 sites in 12 countries.
24 sites in 12 countries
United States6 sites
Duke Clinical Research Institute SC
Durham, North Carolina, 27704
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Columbia University Medical Center SC LAG X2101C
New York, New York, 10032
Memorial Sloan Kettering Cancer Center SC
New York, New York, 10065
Huntsman Cancer Institute Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Cancer Therapy and Research Center UT Health Science Center CTRC 2
San Antonio, Texas, 78229
Australia2 sites
Novartis Investigative Site
Heidelberg, Victoria, 3084
Novartis Investigative Site
Westmead, New South Wales, 2145
Canada2 sites
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
France2 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Germany2 sites
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Würzburg, 97080
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Modena, MO, 41124
Singapore2 sites
Novartis Investigative Site
Singapore, 119228
Novartis Investigative Site
Singapore, 169610
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28009
About this study
Official title: A Phase I/II, Open Label, Multicenter Study of the Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 Administered to Patients With Advanced Malignancies
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation (phase 1) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion (phase 2) which characterized treatment of LAG525 in combination with PDR001 at the MTD or RP2D.
Read the detailed description
This was a Phase 1/2, multi-center, open-label study comprising a Phase 1 dose escalation part followed by a Phase 2 dose expansion part.
During the Phase 1 dose escalation part patients with any advanced solid tumor received the study treatment until the MTD was reached or a lower RP2D was established. The study had the following 3 dose escalation parts: 1) Single-agent LAG525; 2) Single-agent LAG525 in Japanese patients; 3) Combination of LAG525 with PDR001.
Once the RP2D or MTD had been determined in the escalation parts, additional patients were to be enrolled in the Phase 2 expansion parts in order to assess the preliminary anti-tumor activity. Phase 2 expansion cohorts testing single-agent LAG525 were not opened for enrollment based on emerging data including but not limited to preliminary anti-tumor activity. Phase 2 expansion cohorts for the combination of LAG525 with PDR001 were opened and 5 tumor types were assessed: 1) Non-small cell lung cancer (NSCLC); 2) Melanoma; 3) Renal cell cancer (RCC); 4) Mesothelioma; 5) Triple negative breast cancer (TNBC). The efficacy and safety of the combination of LAG525 with PDR001 in these tumor types was assessed in both the PD-1/PD-L1 pre-treated and naïve settings.
- Conditions
- Advanced Solid Tumors
- Being tested
- LAG525, PDR001
- Keywords
- Non-small cell lung cancer, Melanoma, Renal cancer, Mesothelioma, Triple Negative Breast, TNBC, Renal
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Melanoma, Kidney Neoplasms, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAG525Drug
LAG525 was administered via intravenous (i.v.) infusion
PDR001Drug
PDR001 was administered via i.v. infusion
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: LAG525 1 mg/kg Q2W | Experimental | Single-agent LAG525 1 mg/kg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 3 mg/kg Q2W | Experimental | Single-agent LAG525 3 mg/kg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 5 mg/kg Q2W | Experimental | Single-agent LAG525 5 mg/kg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 10 mg/kg Q2W | Experimental | Single-agent LAG525 10 mg/kg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 15 mg/kg Q2W | Experimental | Single-agent LAG525 15 mg/kg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 240 mg Q2W | Experimental | Single-agent LAG525 240 mg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 400 mg Q2W | Experimental | Single-agent LAG525 400 mg Q2W Receives: Drug: LAG525 |
| Phase 1: LAG525 3 mg/kg Q4W | Experimental | Single-agent LAG525 3 mg/kg Q4W Receives: Drug: LAG525 |
| Phase 1: LAG525 5 mg/kg Q4W | Experimental | Single-agent LAG525 5 mg/kg Q4W Receives: Drug: LAG525 |
| Phase 1: LAG525 10 mg/kg Q4W | Experimental | Single-agent LAG525 10 mg/kg Q4W Receives: Drug: LAG525 |
| Phase 1: LAG525 400 mg Q4W | Experimental | Single-agent LAG525 400 mg Q4W Receives: Drug: LAG525 |
| Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W | Experimental | Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W | Experimental | Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W | Experimental | Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W | Experimental | Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W | Experimental | Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W | Experimental | Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W | Experimental | Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W | Experimental | Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W | Experimental | Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W | Experimental | Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W | Experimental | Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W | Experimental | Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W | Experimental | Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W | Experimental | Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W | Experimental | Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W) Receives: Drug: LAG525; Drug: PDR001 |
| Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W | Experimental | Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1 Receives: Drug: LAG525; Drug: PDR001 |
| Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W | Experimental | Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1 Receives: Drug: LAG525; Drug: PDR001 |
| Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W | Experimental | Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1 Receives: Drug: LAG525; Drug: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single-agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Measured: 15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR).
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
ORR is reported by tumor type.
Measured: From start of treatment until end of treatment, assessed up to 2.6 years
Secondary outcomes (41)
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The number of participants in each category (Rest of the World (ROW) patients, Japanese patients) with AEs and SAEs are reported in this record.
Measured: From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 4.5 years.
Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The number of participants with AEs and SAEs is reported for each tumor type.
Measured: From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 2.7 years.
Phase 1: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001
Number of participants with at least one dose reduction of LAG525, at least one dose interruption of LAG525, at least one dose reduction of PDR001 and at least one dose interruption of PDR001.
Japanese patients were not treated with PDR001 and therefore the dose reductions and dose interruptions of this study drug are not applicable.
Measured: From start of treatment until end of treatment, assessed up to 4.4 years.
Phase 2: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001
Number of participants with at least one dose reduction of LAG525, at least one dose interruption of LAG525, at least one dose reduction of PDR001 and at least one dose interruption of PDR001.
The number of participants with dose reductions and dose interruptions of both study drugs is reported for each tumor type.
Measured: From start of treatment until end of treatment, assessed up to 2.6 years.
Phase 1: Relative Dose Intensity (RDI) of LAG525 and PDR001
Relative dose intensity of each study drug is calculated with the following formula: 100 x actual dose intensity (mg/day)/planned dose intensity (mg/day).
Japanese patients were not treated with PDR001 and therefore the RDI of this study drug is not applicable.
Measured: From start of treatment until end of treatment, assessed up to 4.4 years.
Phase 2: Relative Dose Intensity (RDI) of LAG525 and PDR001
Relative dose intensity of each study drug is calculated with the following formula: 100 x actual dose intensity (mg/day)/planned dose intensity (mg/day).
The RDI of both study drugs is reported for each tumor type.
Measured: From start of treatment until end of treatment, assessed up to 2.6 years.
Phase 1: Maximum Observed Serum Concentration (Cmax) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Maximum Observed Serum Concentration (Cmax) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Terminal Elimination Half-life (T1/2) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Terminal Elimination Half-life (T1/2) of LAG525
Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Maximum Observed Serum Concentration (Cmax) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Maximum Observed Serum Concentration (Cmax) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Terminal Elimination Half-life (T1/2) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Terminal Elimination Half-life (T1/2) of PDR001
Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Measured: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Number of Participants With Anti-LAG525 Antibodies
Validated immunoassays were used for screening and confirmation of the presence of anti-LAG525 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Measured: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).
Phase 2: Number of Participants With Anti-LAG525 Antibodies
Validated immunoassays were used for screening and confirmation of the presence of anti-LAG525 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Measured: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).
Phase 1: Number of Participants With Anti-PDR001 Antibodies
Validated immunoassays were used for screening and confirmation of the presence of anti-PDR001 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Measured: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).
Phase 2: Number of Participants With Anti-PDR001 Antibodies
Validated immunoassays were used for screening and confirmation of the presence of anti-PDR001 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record.
Measured: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).
Phase 1: Overall Response Rate (ORR) Per RECIST 1.1
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR).
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
ORR is reported for ROW and Japanese patients.
Measured: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 1: Overall Response Rate (ORR) Per irRC
TTumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). ORR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR) or immune related Partial Response (irPR).
For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters.
ORR is reported for ROW and Japanese patients.
Measured: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 2: Overall Response Rate (ORR) Per irRC
Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). ORR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR) or immune related Partial Response (irPR).
For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters.
ORR is reported by tumor type.
Measured: From start of treatment until end of treatment, assessed up to 2.6 years
Phase 1: Disease Control Rate (DCR) Per RECIST 1.1
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD).
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
DCR is reported for ROW and Japanese patients.
Measured: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 1: Disease Control Rate (DCR) Per irRC
Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). DCR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR), immune related Partial Response (irPR) or immune related Stable Disease (irSD).
For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for irPR or irCR nor an increase in lesions which would qualify for progression.
DCR is reported for ROW and Japanese patients.
Measured: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 2: Disease Control Rate (DCR) Per RECIST 1.1
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD).
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
DCR is reported by tumor type.
Measured: From start of treatment until end of treatment, assessed up to 2.6 years
Phase 2: Disease Control Rate (DCR) Per irRC
Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). DCR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR), immune related Partial Response (irPR) or immune related Stable Disease (irSD).
For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for irPR or irCR nor an increase in lesions which would qualify for progression.
DCR is reported by tumor type.
Measured: From start of treatment until end of treatment, assessed up to 2.6 years
Phase 1: Duration of Response (DOR) Per RECIST 1.1
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1.
Measured: From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 4.4 years
Phase 1: Duration of Response (DOR) Per irRC
DOR only applies to subjects for whom best overall response is immune related complete response (irCR) or immune related partial response (irPR). DOR is defined as the time from the date of first documented response (irCR or irPR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was irRC.
Measured: From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 4.4 years
Phase 2: Duration of Response (DOR) Per RECIST 1.1
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1.
DOR is reported by tumor type.
Measured: From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 2.6 years
Phase 2: Duration of Response (DOR) Per irRC
DOR only applies to subjects for whom best overall response is immune related complete response (irCR) or immune related partial response (irPR). DOR is defined as the time from the date of first documented response (irCR or irPR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was irRC.
DOR is reported by tumor type.
Measured: From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 2.6 years
Phase 1: Progression-free Survival (PFS) Per RECIST 1.1
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1.
PFS is reported for ROW and Japanese patients.
Measured: From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years
Phase 1: Progression-free Survival (PFS) Per irRC
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was irRC.
PFS is reported for ROW and Japanese patients.
Measured: From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years
Phase 2: Progression-free Survival (PFS) Per RECIST 1.1
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1.
PFS is reported by tumor type.
Measured: From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years
Phase 2: Progression-free Survival (PFS) Per irRC
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Tumor response was based on local investigator assessment and the assessment criteria was irRC.
PFS is reported by tumor type.
Measured: From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2015 (estimated)
- Study start17 Jun 2015
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 490 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02460224
- Sponsor's protocol ID
- CLAG525X2101C
- Other IDs
- 2015-000449-21, 2015
- Status last verified
- Jan 2022
- First submitted
- 9 May 2015
- Last updated
- 10 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Rivoltini L, Camisaschi C, Fuca G, Paolini B, Vergani B, Beretta V, Damian S, Duca M, Cresta S, Magni M, Leone BE, Castelli C, de Braud F, De Santis F, Di Nicola M. Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade. Sci Rep. 2024 Feb 9;14(1):3379. doi: 10.1038/s41598-024-54041-9.
PubMed 38336861Schoffski P, Tan DSW, Martin M, Ochoa-de-Olza M, Sarantopoulos J, Carvajal RD, Kyi C, Esaki T, Prawira A, Akerley W, De Braud F, Hui R, Zhang T, Soo RA, Maur M, Weickhardt A, Krauss J, Deschler-Baier B, Lau A, Samant TS, Longmire T, Chowdhury NR, Sabatos-Peyton CA, Patel N, Ramesh R, Hu T, Carion A, Gusenleitner D, Yerramilli-Rao P, Askoxylakis V, Kwak EL, Hong DS. Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) +/- anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies. J Immunother Cancer. 2022 Feb;10(2):e003776. doi: 10.1136/jitc-2021-003776.
PubMed 35217575
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open Label, Multicenter Study of the Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 Administered to Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02460224
- Acronym / sponsor ID
- CLAG525X2101C
- Conditions
- Advanced Solid Tumors
- Keywords
- Non-small cell lung cancer, Melanoma, Renal cancer, Mesothelioma, Triple Negative Breast, TNBC, Renal
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 490 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 Jun 2015 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 2 Jun 2015 (estimated)
- Results
- Posted 10 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation (phase 1) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion (phase 2) which characterized treatment of LAG525 in combination with PDR001 at the MTD or RP2D.
Detailed description
This was a Phase 1/2, multi-center, open-label study comprising a Phase 1 dose escalation part followed by a Phase 2 dose expansion part.
During the Phase 1 dose escalation part patients with any advanced solid tumor received the study treatment until the MTD was reached or a lower RP2D was established. The study had the following 3 dose escalation parts: 1) Single-agent LAG525; 2) Single-agent LAG525 in Japanese patients; 3) Combination of LAG525 with PDR001.
Once the RP2D or MTD had been determined in the escalation parts, additional patients were to be enrolled in the Phase 2 expansion parts in order to assess the preliminary anti-tumor activity. Phase 2 expansion cohorts testing single-agent LAG525 were not opened for enrollment based on emerging data including but not limited to preliminary anti-tumor activity. Phase 2 expansion cohorts for the combination of LAG525 with PDR001 were opened and 5 tumor types were assessed: 1) Non-small cell lung cancer (NSCLC); 2) Melanoma; 3) Renal cell cancer (RCC); 4) Mesothelioma; 5) Triple negative breast cancer (TNBC). The efficacy and safety of the combination of LAG525 with PDR001 in these tumor types was assessed in both the PD-1/PD-L1 pre-treated and naïve settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 29
| Arm | Type | Receives |
|---|---|---|
| Phase 1: LAG525 1 mg/kg Q2W | Experimental | Drug: LAG525Single-agent LAG525 1 mg/kg Q2W |
| Phase 1: LAG525 3 mg/kg Q2W | Experimental | Drug: LAG525Single-agent LAG525 3 mg/kg Q2W |
| Phase 1: LAG525 5 mg/kg Q2W | Experimental | Drug: LAG525Single-agent LAG525 5 mg/kg Q2W |
| Phase 1: LAG525 10 mg/kg Q2W | Experimental | Drug: LAG525Single-agent LAG525 10 mg/kg Q2W |
| Phase 1: LAG525 15 mg/kg Q2W | Experimental | Drug: LAG525Single-agent LAG525 15 mg/kg Q2W |
| Phase 1: LAG525 240 mg Q2W | Experimental | Drug: LAG525Single-agent LAG525 240 mg Q2W |
| Phase 1: LAG525 400 mg Q2W | Experimental | Drug: LAG525Single-agent LAG525 400 mg Q2W |
| Phase 1: LAG525 3 mg/kg Q4W | Experimental | Drug: LAG525Single-agent LAG525 3 mg/kg Q4W |
| Phase 1: LAG525 5 mg/kg Q4W | Experimental | Drug: LAG525Single-agent LAG525 5 mg/kg Q4W |
| Phase 1: LAG525 10 mg/kg Q4W | Experimental | Drug: LAG525Single-agent LAG525 10 mg/kg Q4W |
| Phase 1: LAG525 400 mg Q4W | Experimental | Drug: LAG525Single-agent LAG525 400 mg Q4W |
| Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W) |
| Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W) |
| Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W) |
| Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W) |
| Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W) |
| Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W) |
| Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) |
| Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W) |
| Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W) |
| Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W) |
| Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W) |
| Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W) |
| Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W) |
| Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W) |
| Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W) |
| Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1 |
| Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1 |
| Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W | Experimental | Drug: LAG525, Drug: PDR001Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists
- Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have had disease progression following their last prior therapy and fit into one of the following groups:
- Group 1: NSCLC
- Group 2: Melanoma
- Group 3: Renal cancer
Key exclusion criteria (10 listed)
- History of severe hypersensitivity reactions to study treatment ingredients or other mAbs
- Active, known or suspected autoimmune disease
- Active infection requiring systemic antibiotic therapy
- HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Patients receiving chronic treatment with systemic steroid therapy, other than replacement-dose corticosteroids in the setting of adrenal insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAG525LAG525 was administered via intravenous (i.v.) infusion | Drug | Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W, Phase 1: LAG525 1 mg/kg Q2W, Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W, Phase 1: LAG525 10 mg/kg Q2W, Phase 1: LAG525 10 mg/kg Q4W, Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W, Phase 1: LAG525 15 mg/kg Q2W, Phase 1: LAG525 240 mg Q2W, Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W, Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W, Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W, Phase 1: LAG525 3 mg/kg Q2W, Phase 1: LAG525 3 mg/kg Q4W, Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W, Phase 1: LAG525 400 mg Q2W, Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W, Phase 1: LAG525 400 mg Q4W, Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W, Phase 1: LAG525 5 mg/kg Q2W, Phase 1: LAG525 5 mg/kg Q4W, Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W, Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W, Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W, Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W, Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W, Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W, Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W, Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W, Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W |
| PDR001PDR001 was administered via i.v. infusion | Drug | Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W, Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W, Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W, Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W, Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W, Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W, Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W, Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W, Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W, Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W, Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W, Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W, Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W, Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W, Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W, Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W, Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W, Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W |
Primary outcome
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: 15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single-agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1
Time frame: From start of treatment until end of treatment, assessed up to 2.6 years
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. ORR is reported by tumor type.
41 secondary outcomes
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 4.5 years.
Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 2.7 years.
Phase 1: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001
Time frame: From start of treatment until end of treatment, assessed up to 4.4 years.
Phase 2: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001
Time frame: From start of treatment until end of treatment, assessed up to 2.6 years.
Phase 1: Relative Dose Intensity (RDI) of LAG525 and PDR001
Time frame: From start of treatment until end of treatment, assessed up to 4.4 years.
Phase 2: Relative Dose Intensity (RDI) of LAG525 and PDR001
Time frame: From start of treatment until end of treatment, assessed up to 2.6 years.
Phase 1: Maximum Observed Serum Concentration (Cmax) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Maximum Observed Serum Concentration (Cmax) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Terminal Elimination Half-life (T1/2) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Terminal Elimination Half-life (T1/2) of LAG525
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Maximum Observed Serum Concentration (Cmax) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Maximum Observed Serum Concentration (Cmax) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Terminal Elimination Half-life (T1/2) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).
Phase 2: Terminal Elimination Half-life (T1/2) of PDR001
Time frame: pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).
Phase 1: Number of Participants With Anti-LAG525 Antibodies
Time frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).
Phase 2: Number of Participants With Anti-LAG525 Antibodies
Time frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).
Phase 1: Number of Participants With Anti-PDR001 Antibodies
Time frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).
Phase 2: Number of Participants With Anti-PDR001 Antibodies
Time frame: Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).
Phase 1: Overall Response Rate (ORR) Per RECIST 1.1
Time frame: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 1: Overall Response Rate (ORR) Per irRC
Time frame: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 2: Overall Response Rate (ORR) Per irRC
Time frame: From start of treatment until end of treatment, assessed up to 2.6 years
Phase 1: Disease Control Rate (DCR) Per RECIST 1.1
Time frame: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 1: Disease Control Rate (DCR) Per irRC
Time frame: From start of treatment until end of treatment, assessed up to 4.4 years
Phase 2: Disease Control Rate (DCR) Per RECIST 1.1
Time frame: From start of treatment until end of treatment, assessed up to 2.6 years
Phase 2: Disease Control Rate (DCR) Per irRC
Time frame: From start of treatment until end of treatment, assessed up to 2.6 years
Phase 1: Duration of Response (DOR) Per RECIST 1.1
Time frame: From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 4.4 years
Phase 1: Duration of Response (DOR) Per irRC
Time frame: From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 4.4 years
Phase 2: Duration of Response (DOR) Per RECIST 1.1
Time frame: From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 2.6 years
Phase 2: Duration of Response (DOR) Per irRC
Time frame: From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 2.6 years
Phase 1: Progression-free Survival (PFS) Per RECIST 1.1
Time frame: From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years
Phase 1: Progression-free Survival (PFS) Per irRC
Time frame: From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years
Phase 2: Progression-free Survival (PFS) Per RECIST 1.1
Time frame: From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38336861Rivoltini L, Camisaschi C, Fuca G, Paolini B, Vergani B, Beretta V, Damian S, Duca M, Cresta S, Magni M, Leone BE, Castelli C, de Braud F, De Santis F, Di Nicola M. Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade. Sci Rep. 2024 Feb 9;14(1):3379. doi: 10.1038/s41598-024-54041-9.
- Derived from this study: PubMed 35217575Schoffski P, Tan DSW, Martin M, Ochoa-de-Olza M, Sarantopoulos J, Carvajal RD, Kyi C, Esaki T, Prawira A, Akerley W, De Braud F, Hui R, Zhang T, Soo RA, Maur M, Weickhardt A, Krauss J, Deschler-Baier B, Lau A, Samant TS, Longmire T, Chowdhury NR, Sabatos-Peyton CA, Patel N, Ramesh R, Hu T, Carion A, Gusenleitner D, Yerramilli-Rao P, Askoxylakis V, Kwak EL, Hong DS. Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) +/- anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies. J Immunother Cancer. 2022 Feb;10(2):e003776. doi: 10.1136/jitc-2021-003776.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Related trials for Advanced Solid Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
24 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LAG525 and PDR001 in people with Advanced Solid Tumors, run by Novartis Pharmaceuticals at 24 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Australia, Canada, France, Germany and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: 15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02460224, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2022.