Triple Negative Breast CancerPhase 1/2NCT02807844
Phase Ib/II Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies
A Phase 1/2 study testing MCS110 and PDR001 in people with Triple Negative Breast Cancer and Pancreatic Carcinoma, run by Novartis Pharmaceuticals at 20 sites in 11 countries.
Trial summary
The purpose of this study of MCS110 with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the combination of MCS110 with PDR001 in adult patients with solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer, Pancreatic Carcinoma, Melanoma
- What is being tested?
- MCS110 and PDR001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 141 participants
- Where
- 20 sitesin 11 countries
- Study dates
- 29 Jun 2016to 4 Jun 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
Main Inclusion Criteria:
- Signed informed consent prior to any procedures
- Phase Ib part: Adult patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
- Phase II part: Adult patients with advanced solid tumors who have received standard therapy (no more than 3 prior lines of treatment) or are intolerant of standard therapy, have progressed following their last prior therapy, and fit into one of the following groups:
- Group 1: TNBC who did not receive prior anti-PD-1/PD-L1 treatment
- Group 2: Pancreatic adenocarcinoma who did not receive prior anti-PD-1/PD-L1 treatment
- Group 3: Endometrial carcinoma who did not receive prior anti-PD-1/PD-L1 treatment
- Group 4: Melanoma who progressed on prior anti-PD-1/PD-L1 treatment.
Main Exclusion Criteria:
- Patients with the following:
- Symptomatic central nervous system (CNS) metastases or those requiring local CNS-directed therapy.
- Abnormal liver, renal, or blood lab values.
- Impaired cardiac function or clinically significant cardiac disease.
- Active autoimmune disease or documented autoimmune disease within 3 years of screening.
- Active infection requiring antibiotic therapy.
- Known HIV, active hepatitis B or C virus.
- Concurrent malignant disease.
- Patients who received systemic anticancer therapy, major surgery, or radiotherapy within 2 weeks of study treatment, or live vaccines within 4 weeks of study treatment.
- Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy.
- Patients who used hematopoietic colony-stimulating growth factors within 2 weeks of study treatment.
Trial locations and contacts
20 sites in 11 countries.
20 sites in 11 countries
United States4 sites
Dana Farber Cancer Center
Boston, Massachusetts, 02215
The West Clinic
Germantown, Tennessee, 38138
MD Anderson Cancer Center
Houston, Texas, 77030
Washington University School of Medicine
St Louis, Missouri, 63123
Switzerland3 sites
Novartis Investigative Site
Chur, 7000
Novartis Investigative Site
Geneva, CH 1211
Novartis Investigative Site
Zurich, 8091
Germany2 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Ulm, 89081
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
South Korea2 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 05505
Spain2 sites
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Valencia, Valencia, 46010
About this study
Official title: A Phase Ib/II, Open Label, Multicenter Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies
The purpose of this study of MCS110 with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the combination of MCS110 with PDR001 in adult patients with solid tumors.
Read the detailed description
Combined treatment with MCS110 and PDR001 was expected to result in Tumor-associated macrophages (TAM) depletion, enhanced T-cell activation and synergistic antitumor activity in the clinical setting.
This study was a Phase Ib/II, multi-center, open label study starting with a Phase Ib dose escalation part followed by a Phase II part. MCS110 and PDR001 were administered i.v. Q3W until the patient experienced unacceptable toxicity, progressive disease as per irRC and/or treatment was discontinued at the discretion of the investigator or the patient. Patients were not to discontinue treatment based on progressive disease per Response evaluation criteria in solid tumors (RECIST) v1.1. During the Phase Ib part of the study, cohorts of patients were treated with increasing doses of MCS110 and PDR001 every 3 weeks until a Recommended Phase 2 Dose (RP2D) was determined for this treatment combination.
To assure that the combination RP2D did not exceed the Maximum tolerated dose (MTD), the combination MCS110 and PDR001 dose escalation was guided by a Bayesian logistic regression model (BLRM) with overdose control (EWOC) principle based on dose limiting toxicity data in the context of available safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) information. Once the MTD and/or RP2D was declared, additional patients were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of MCS110 in combination with PDR001 in anti-PD1/PD-L1-naive triple negative breast cancer (TNBC), pancreatic (PC), endometrial carcinoma (EC) and anti PD1/PD-L1-resistance melanoma (ME).
- Being tested
- MCS110, PDR001
- Keywords
- Triple negative breast cancer, Pancreatic carcinoma, Melanoma, Endometrial Carcinoma, Immuno oncology, Monoclonal antibody, PDR001, MCS110, Advanced malignancies, metasteses, advanced cancer, malignant
- Medical subject headings
- Triple Negative Breast Neoplasms, Pancreatic Neoplasms, Melanoma, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MCS110Drug
Also called colony-stimulating factor-1 [CSF-1])
MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
PDR001Drug
MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
| Study group | Role | What they receive |
|---|---|---|
| Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W | Experimental | Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W Receives: Drug: MCS110; Drug: PDR001 |
| Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W | Experimental | Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W Receives: Drug: MCS110; Drug: PDR001 |
| Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W Receives: Drug: MCS110; Drug: PDR001 |
| Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W Receives: Drug: MCS110; Drug: PDR001 |
| Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W Receives: Drug: MCS110; Drug: PDR001 |
| Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W Receives: Drug: MCS110; Drug: PDR001 |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC | Experimental | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) Receives: Drug: MCS110; Drug: PDR001 |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC | Experimental | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) Receives: Drug: MCS110; Drug: PDR001 |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC | Experimental | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) Receives: Drug: MCS110; Drug: PDR001 |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME | Experimental | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME) Receives: Drug: MCS110; Drug: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Percentage of Participants With Adverse Events, as a Measure of Safety
Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.
Measured: From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib
Phase II : Overall Response Rate (ORR) - Per RECIST v1.1
Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Measured: 4 years
Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per RECIST v1.1 - Mean
Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS)
Measured: 4 years
Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per RECIST v1.1
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
Measured: 4 years
Phase II: Bayesian Inference of Clinical Benefit Rate - Per RECIST v1.1- Mean
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
Measured: 4 years
Phase Ib: Planned Dose Intensity - MCS110
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Relative Dose Intensity - MCS110
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Planned Dose Intensity - PDR001
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Relative Dose Intensity - PDR001
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Number of Participants With Dose Reductions
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Number of Dose Interruptions Per Participant
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Number of Subjects With at Least One Dose Interruption
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Measured: Measured up to a max of 112.4 weeks
Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment
Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading.
Measured: the first 2 cycles of study treatment; cycle = 21 days (i.e., at day 42)
Secondary outcomes (28)
Phase II : Overall Response Rate (ORR) - Per irRC
Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC) (FAS)
Measured: 4 years
Phase Ib: Overall Response Rate (ORR)
Phase Ib: Overall Response Rate (Complete response (CR) or Partial response (PR)), per RECIST v1.1 and per immune related Response criteria (irRC)
Measured: 4 years
Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per irRC - Mean
Phase II: Overall Response Rate (Complete response (CR) or Partial response (PR)) (with confirmation) as per investigator based on immune related Response criteria (irRC)- mean (FAS)
Measured: 4 years
Phase 1b: Clinical Benefit Rate (CBR)
Phase 1b: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)
Measured: 4 years
Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per irRC
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per immune related Response criteria (irRC)
Measured: 4 years
Phase II: Bayesian Inference of Clinical Benefit Rate - Per irRC - Mean
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on immune related Response criteria (irRC)- mean (FAS)
Measured: 4 years
Phase 1b and Phase II: Progression Free Survival Based on Investigator Assessment as Per RECIST v1.1 and Per Immune Related Response Criteria (irRC) - Using Kaplan-Meier Method - Median
Phase 1b and Phase II: Progression Free Survival. Progression is defined as a 20% increase in the sum of diameter of measurable lesions taking as reference the smallest sum of diameter recorded at or after baseline, or worsening of non-measurable lesions or the appearance of new lesions, using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or Per Immune Related Response Criteria (irRC). Unlike RECIST 1.1, PD per irRC requires confirmation at a new assessment after at least 4 weeks - using Kaplan-Meier method - Median.
Measured: Up to year 4
Phase 1b and Phase II: Overall Survival - Using Kaplan-Meier Method - Median
Phase 1b and Phase II: Overall Survival - using Kaplan-Meier method - Median
Measured: Up to year 4
Phase 1b and Phase II: Duration of Response (DOR)
Phase 1b and Phase II: Duration of Response (DOR) per RECIST v1.1 and per immune related Response criteria (irRC)
Measured: 4 years
Phase 1b and Phase II: Disease Control Rate (DCR)
Phase 1b and Phase II: Disease Control Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per RECIST v1.1 and per immune related Response criteria (irRC)
Measured: 4 years
Phase II: Percentage of Participants With Adverse Events, as a Measure of Safety
Phase II: To further characterize the safety and tolerability of MCS110 given in combination with PDR001
Measured: From start of treatment to a maximum timeframe of 92.4 weeks for phase II.
Phase Ib and Phase II: Immunogenicity MCS110
Phase Ib and Phase II: Presence of anti-MCS110 antibodies
Measured: 4 years
Phase Ib and Phase II: Immunogenicity PDR001
Phase Ib and Phase II: Presence of anti-PDR001 antibodies
Measured: 4 years
Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf
Phase Ib and Phase II: PK Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time
× volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) - MCS110
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf
Phase Ib and Phase II: Pharmacokinetics (PK) Parameters - AUClast, which is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time
× volume-1); and AUCinf, which is the AUC from time zero to infinity (mass × time × volume-1) and AUCinf - PDR001
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast
Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - MCS110
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast
Phase Ib and Phase II: PK Parameters - Cmax, which is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1); and Clast - PDR001
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax
Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - MCS110
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax
Phase Ib and Phase II: PK Parameters - Tmax, which is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) - PDR001
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2
Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - MCS110
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2
Phase Ib and Phase II: PK Parameters - T1/2, which is the terminal half-life associated with the terminal slope of a semi logarithmic concentration time curve (time) - PDR001
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL
Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - MCS110
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL
Phase Ib and Phase II: PK Parameters - CL, which is the total body clearance of drug from the plasma (volume × time-1) - PDR001
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz
Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - MCS110
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz
Phase Ib and Phase II: PK Parameters - Vz, which is the apparent volume of distribution during terminal phase (volume) - PDR001
Measured: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation Ratio (AR)
Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - MCS110
Measured: cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation Ratio (AR)
Phase Ib and Phase II: PK Parameters - Accumulation ratio (AR), which is the AUClast (multiple Dose)/AUClast (single dose) (for cycle 4 only) - PDR001
Measured: cycle 4 (day 84)
Phase Ib and Phase II: All Collected Deaths
On treatment deaths are reported from the start of treatment until end of study treatment plus 30 days, up to maximum duration of 116.4 weeks for phase Ib and 92.4 weeks for phase II. Deaths post treatment survival follow up are reported after the on-treatment period, up to a maximum timeframe of 46 months (3.8 years).
Measured: For ontreatment deaths: up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II. For total deaths: up to 3.8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study start29 Jun 2016
- Primary completion4 Jun 2020
- Study completion4 Jun 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 (1)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast CancerStudies 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
- 141 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
- NCT02807844
- Sponsor's protocol ID
- CMCS110Z2102
- Other IDs
- 2016-000210-29, 2016
- Status last verified
- Jul 2021
- First submitted
- 17 Jun 2016
- Last updated
- 11 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Ahmed J, Stephen B, Yang Y, Kwiatkowski E, Ejezie CL, Pant S. Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies. J Immunother Precis Oncol. 2024 May 2;7(2):73-81. doi: 10.36401/JIPO-23-16. eCollection 2024 May.
PubMed 38721402
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Open Label, Multicenter Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02807844
- Acronym / sponsor ID
- CMCS110Z2102
- Keywords
- Triple negative breast cancer, Pancreatic carcinoma, Melanoma, Endometrial Carcinoma, Immuno oncology, Monoclonal antibody, PDR001, MCS110
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2016 (actual)
- Primary completion
- 4 Jun 2020 (actual)
- Study completion
- 4 Jun 2020 (actual)
- First posted
- 21 Jun 2016 (estimated)
- Results
- Posted 11 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study of MCS110 with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the combination of MCS110 with PDR001 in adult patients with solid tumors.
Detailed description
Combined treatment with MCS110 and PDR001 was expected to result in Tumor-associated macrophages (TAM) depletion, enhanced T-cell activation and synergistic antitumor activity in the clinical setting.
This study was a Phase Ib/II, multi-center, open label study starting with a Phase Ib dose escalation part followed by a Phase II part. MCS110 and PDR001 were administered i.v. Q3W until the patient experienced unacceptable toxicity, progressive disease as per irRC and/or treatment was discontinued at the discretion of the investigator or the patient. Patients were not to discontinue treatment based on progressive disease per Response evaluation criteria in solid tumors (RECIST) v1.1. During the Phase Ib part of the study, cohorts of patients were treated with increasing doses of MCS110 and PDR001 every 3 weeks until a Recommended Phase 2 Dose (RP2D) was determined for this treatment combination.
To assure that the combination RP2D did not exceed the Maximum tolerated dose (MTD), the combination MCS110 and PDR001 dose escalation was guided by a Bayesian logistic regression model (BLRM) with overdose control (EWOC) principle based on dose limiting toxicity data in the context of available safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) information. Once the MTD and/or RP2D was declared, additional patients were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of MCS110 in combination with PDR001 in anti-PD1/PD-L1-naive triple negative breast cancer (TNBC), pancreatic (PC), endometrial carcinoma (EC) and anti PD1/PD-L1-resistance melanoma (ME).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W | Experimental | Drug: MCS110, Drug: PDR001Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W |
| Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W | Experimental | Drug: MCS110, Drug: PDR001Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W |
| Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Drug: MCS110, Drug: PDR001Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Drug: MCS110, Drug: PDR001Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Drug: MCS110, Drug: PDR001Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W | Experimental | Drug: MCS110, Drug: PDR001Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC | Experimental | Drug: MCS110, Drug: PDR001Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC | Experimental | Drug: MCS110, Drug: PDR001Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC | Experimental | Drug: MCS110, Drug: PDR001Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME | Experimental | Drug: MCS110, Drug: PDR001Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| MCS110Also: colony-stimulating factor-1 [CSF-1])MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion. | Drug | Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC, Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME, Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC, Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC, Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W, Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W, Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W, Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W, Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W, Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W |
| PDR001MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion. | Drug | Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC, Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME, Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC, Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC, Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W, Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W, Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W, Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W, Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W, Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W |
Primary outcome
Phase Ib: Percentage of Participants With Adverse Events, as a Measure of Safety
Time frame: From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib
Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.
Phase II : Overall Response Rate (ORR) - Per RECIST v1.1
Time frame: 4 years
Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per RECIST v1.1 - Mean
Time frame: 4 years
Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS)
Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per RECIST v1.1
Time frame: 4 years
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
Phase II: Bayesian Inference of Clinical Benefit Rate - Per RECIST v1.1- Mean
Time frame: 4 years
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) > 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
Phase Ib: Planned Dose Intensity - MCS110
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
Phase Ib: Relative Dose Intensity - MCS110
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).
Phase Ib: Planned Dose Intensity - PDR001
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
Phase Ib: Relative Dose Intensity - PDR001
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).
Phase Ib: Number of Participants With Dose Reductions
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Phase Ib: Number of Dose Interruptions Per Participant
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Phase Ib: Number of Subjects With at Least One Dose Interruption
Time frame: Measured up to a max of 112.4 weeks
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) During the First 2 Cycles of Study Treatment
Time frame: the first 2 cycles of study treatment; cycle = 21 days (i.e., at day 42)
Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading.
28 secondary outcomes
Phase II : Overall Response Rate (ORR) - Per irRC
Time frame: 4 years
Phase Ib: Overall Response Rate (ORR)
Time frame: 4 years
Phase II : Bayesian Inference of Overall Response Rate (ORR) - Per irRC - Mean
Time frame: 4 years
Phase 1b: Clinical Benefit Rate (CBR)
Time frame: 4 years
Phase II: Clinical Benefit Rate (Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) > 4 Month)) - Per irRC
Time frame: 4 years
Phase II: Bayesian Inference of Clinical Benefit Rate - Per irRC - Mean
Time frame: 4 years
Phase 1b and Phase II: Progression Free Survival Based on Investigator Assessment as Per RECIST v1.1 and Per Immune Related Response Criteria (irRC) - Using Kaplan-Meier Method - Median
Time frame: Up to year 4
Phase 1b and Phase II: Overall Survival - Using Kaplan-Meier Method - Median
Time frame: Up to year 4
Phase 1b and Phase II: Duration of Response (DOR)
Time frame: 4 years
Phase 1b and Phase II: Disease Control Rate (DCR)
Time frame: 4 years
Phase II: Percentage of Participants With Adverse Events, as a Measure of Safety
Time frame: From start of treatment to a maximum timeframe of 92.4 weeks for phase II.
Phase Ib and Phase II: Immunogenicity MCS110
Time frame: 4 years
Phase Ib and Phase II: Immunogenicity PDR001
Time frame: 4 years
Phase Ib and Phase II: Pharmacokinetics of MCS110 - AUClast and AUCinf
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - AUClast and AUCinf
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Cmax and Clast
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Cmax and Clast
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Tmax
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Tmax
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - T1/2
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - T1/2
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - CL
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - CL
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Vz
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Vz
Time frame: cycle 1 (day 21) and cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of MCS110 - Accumulation Ratio (AR)
Time frame: cycle 4 (day 84)
Phase Ib and Phase II: Pharmacokinetics of PDR001 - Accumulation Ratio (AR)
Time frame: cycle 4 (day 84)
Phase Ib and Phase II: All Collected Deaths
Time frame: For ontreatment deaths: up to maximum timeframe of 116.4 weeks for phase Ib and 92.4 weeks for phase II. For total deaths: up to 3.8 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38721402Ahmed J, Stephen B, Yang Y, Kwiatkowski E, Ejezie CL, Pant S. Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies. J Immunother Precis Oncol. 2024 May 2;7(2):73-81. doi: 10.36401/JIPO-23-16. eCollection 2024 May.
- Individual participant dataSharing planned: Yes. 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.
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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
20 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MCS110 and PDR001 in people with Triple Negative Breast Cancer and Pancreatic Carcinoma, run by Novartis Pharmaceuticals at 20 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 11 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Switzerland, Germany, Italy, South Korea and 6 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 11 Aug 2021). 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 Ib: Percentage of Participants With Adverse Events, as a Measure of Safety (time frame: From start of treatment to a maximum timeframe of 116.4 weeks for phase Ib). The study lists 13 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 NCT02807844, which also lists 1 linked publication.
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 11 Aug 2021.