Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - AdenocarcinomaPhase 1NCT02900664
A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
A Phase 1 study testing PDR001, ACZ885 and CJM112 in people with Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma, run by Novartis Pharmaceuticals at 23 sites in 9 countries.
Trial summary
The purpose of this study was to combine the PDR001 checkpoint inhibitor with each of four agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma
- What is being tested?
- PDR001, ACZ885 and CJM112
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 283 participants
- Where
- 23 sitesin 9 countries
- Study dates
- 23 Aug 2016to 17 Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available.
- Patients must fit into one of the following groups:
- Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry)
- Non-small cell lung cancer (NSCLC) (adenocarcinoma)
- Triple Negative Breast Cancer (TNBC) (D
- ECOG Performance Status ≤ 2
Show all 9Show fewer
- Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, and again during therapy on this study.
- Prior therapy with PD-1/PDL-1 inhibitors is allowed provided any toxicity attributed to prior PD-1- or PD-L1-directed therapy did not lead to discontinuation of therapy.
- Written informed consent must be obtained prior to any screening procedures other than procedures performed as part of standard of care.
Who cannot join
- 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 severe hypersensitivity reactions to other monoclonal antibodies.
- Out of range laboratory values for measures of hepatic and renal function, electrolytes and blood counts
- Impaired cardiac function or clinically significant cardiac disease.
- Patients with active, known or suspected autoimmune disease.
- Human Immunodeficiency Virus infection at screening.
Show all 39Show fewer
- Escalation part: Active Hepatitis B (HBV) or Hepatitis C (HCV) virus infection at screening.
- Expansion part: Patients with active HBV or HCV are excluded, excepting those patients undergoing treatment for HBV or HCV.
- Malignant disease, other than that being treated in this study.
- Recent systemic anti-cancer therapy
- Active infection requiring systemic antibiotic therapy.
- Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids in the setting of adrenal insufficiency or treatment with low, stable dose of steroid (<10mg/ day prednisone or equivalent) for stable CNS metastatic disease.
- Patients receiving systemic treatment with any immunosuppressive medication, excepting the above
- Use of any live vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
- Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment.
- Presence of ≥ CTCAE grade 2 toxicity (except alopecia and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
- Recent use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF)
- Additional exclusion criteria for Combination arm PDR001+canakinumab and single-agent canakinumab
- Patients with tuberculosis (TB). Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
- Patients who have been infected with HBV or HCV including those with inactive disease.
- Additional exclusion criteria for Combination arm PDR001+CJM112
- Patients with TB. Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
- Patients with history of and/or active inflammatory bowel disease.
- Active skin or soft tissue infection including cellulitis, erysipelas, impetigo, furuncle,carbuncle, abscess, or fasciitis.
- Active candida infection, including mucocutaneous infection or history of invasive candidiasis.
- Additional exclusion criteria for Combination arm PDR001+trametinib
- Patients with history of retinal vein oclusion.
- Patients with history of interstitial lung disease or pneumonitis.
- Patients with cardiomyopathy and/or LVEF < LLN.
- Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners.
- Hemoglobin (Hgb) < 9 g/dL without growth factor or transfusion support
- Women of child-bearing potential using hormonal contraception, unless an additional contraception method is also used according to the Mekinist® label.
- Additional exclusion criteria for Combination arm PDR001+EGF816
- NSCLC patients with EGFR mutant tumors.
- Strong inhibitors and strong inducers of CYP3A4 should not be used concomitantly.
- Patients with history of interstitial lung disease.
- Patients who have been infected with HBV or HCV including those with inactive disease.
- Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners
- Patients cannot have received radiotherapy to lung fields within 6 months of study treatment start.
Trial locations and contacts
23 sites in 9 countries.
23 sites in 9 countries
United States4 sites
Sidney Kimmel Comprehensive Cancer Center SC-3
Baltimore, Maryland, 21287-0013
Dana Farber Cancer Center
Boston, Massachusetts, 02215
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
France4 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Toulouse, 31059
Novartis Investigative Site
Villejuif, 94800
Spain4 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28050
Belgium2 sites
Novartis Investigative Site
Brussels, BE-B-1200
Novartis Investigative Site
Wilrijk, 2610
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Italy2 sites
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Rozzano, MI, 20089
Singapore2 sites
Novartis Investigative Site
Singapore, 119228
Novartis Investigative Site
Singapore, 169610
Taiwan2 sites
Novartis Investigative Site
Tainan, 70403
Novartis Investigative Site
Taoyuan, 33305
About this study
Official title: Phase Ib, Open-label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacodynamics (PD) of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
The purpose of this study was to combine the PDR001 checkpoint inhibitor with each of four agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations.
Read the detailed description
This was a Phase Ib, multi-center, open-label study, to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 in combination with canakinumab, CJM112, trametinib and EGF816 and single agent (s.a.) canakinumab in subjects with Triple Negative Breast Cancer (TNBC), Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC). The study comprised a dose escalation part for combination treatments only, followed by a dose expansion part.
- Being tested
- PDR001, ACZ885, CJM112, TMT212, EGF816
- Keywords
- CRC, TNBC, NSCLC (adenocarcinoma), Immunomodulation, Biomarkers, Bayesian logistic regression model, PDR001, Immunotherapy, Rectal cancer, Metastatic adenocarcinoma, Colorectal cancer, colon cancer, bowel cancer, cancer of the colon and rectum, Colorectal adenocarcinoma, adenocarcinoma, colon, cancer, large intestine, large intestine cancer
- Medical subject headings
- Colorectal Neoplasms, Triple Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma, Rectal Neoplasms, Colonic Neoplasms, Intestinal Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Biological
Also called Spartalizumab/PDR001
Powder for solution for infusion
ACZ885Biological
Also called canakinumab
Solution for injection
CJM112Biological
Solution for infusion
TMT212Drug
Also called trametinib
Tablets
EGF816Drug
Also called Nazartinib
Tablets
| Study group | Role | What they receive |
|---|---|---|
| PDR + ACZ 100mg Q8W | Experimental | PDR + ACZ 100mg Q8W Receives: Biological: PDR001; Biological: ACZ885 |
| PDR + ACZ 300mg Q8W | Experimental | PDR + ACZ 300mg Q8W Receives: Biological: PDR001; Biological: ACZ885 |
| PDR + ACZ RDE TNBC | Experimental | PDR + ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC) Receives: Biological: PDR001; Biological: ACZ885 |
| PDR + ACZ RDE NSCLC | Experimental | PDR + ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC) Receives: Biological: PDR001; Biological: ACZ885 |
| PDR + ACZ RDE CRC | Experimental | PDR + ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC) Receives: Biological: PDR001; Biological: ACZ885 |
| PDR + CJM 25mg Q4W | Experimental | PDR + CJM 25mg Q4W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 75mg Q4W | Experimental | PDR + CJM 75mg Q4W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 225mg Q4W | Experimental | PDR + CJM 225mg Q4W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 450mg Q4W | Experimental | PDR + CJM 450mg Q4W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 450mg Q2W | Experimental | PDR + CJM 450mg Q2W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 900mg Q4W | Experimental | PDR + CJM 900mg Q4W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 900mg Q2W | Experimental | PDR + CJM 900mg Q2W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + CJM 1200mg Q4W | Experimental | PDR + CJM 1200mg Q4W Receives: Biological: PDR001; Biological: CJM112 |
| PDR + TMT 0.5mg QD | Experimental | PDR + TMT 0.5mg QD Receives: Biological: PDR001; Drug: TMT212 |
| PDR + TMT 1mg QD | Experimental | PDR + TMT 1mg QD Receives: Biological: PDR001; Drug: TMT212 |
| PDR + TMT 1mg QD, 3 Weeks on/1 Week off | Experimental | PDR + TMT 1mg QD, 3 Weeks on/1 Week off Receives: Biological: PDR001; Drug: TMT212 |
| PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off | Experimental | PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off Receives: Biological: PDR001; Drug: TMT212 |
| PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off | Experimental | PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off Receives: Biological: PDR001; Drug: TMT212 |
| PDR + EGF816 25mg QD | Experimental | PDR + EGF816 25mg QD Receives: Drug: EGF816 |
| PDR + EGF816 50mg QD | Experimental | PDR + EGF816 50mg QD Receives: Drug: EGF816 |
| s.a. ACZ RDE TNBC | Experimental | Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC) Receives: Biological: ACZ885 |
| s.a. ACZ RDE NSCLC | Experimental | Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC) Receives: Biological: ACZ885 |
| s.a. ACZ RDE CRC | Experimental | Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC) Receives: Biological: ACZ885 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Measured: Throughout the study at every visit, an average of 1 year
Changes between baseline and post-baseline laboratory parameters and vital signs.
Measured: Baseline and throughout the study at every visit, an average of 1 year
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
Measured: During the first two cycles; Cycle = 28 days
Frequency of dose interruptions
Measured: Throughout the study at every visit, an average of 1 year
Dose intensities
Measured: Throughout the study at every visit, an average of 1 year
Severity of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Measured: Throughout the study at every visit, an average of 1 year
Frequency of dose reductions
Measured: Throughout the study at every visit, an average of 1 year
Secondary outcomes (16)
Key secondary: Histopathology of tumor infiltrating lymphocytes (TILs)
Measured: Baseline and approximately after 2 cycles of treatment and at disease progression; Cycle = 28 days
Changes from baseline in electrocardiogram (ECG) parameters
Measured: Baseline and end of treatment, an average of 1 year
Best overall response (BOR)
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Progression free survival (PFS) per irRC and RECIST v1.1
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Treatment Free Survival (TFS)
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Presence and/or concentration of anti-PDR001 antibodies.
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Serum concentration of PDR001, canakinumab, CJM112
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Plasma concentrations of trametinib and EGF816
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Key secondary: Histopathology of myeloid cell infiltrate by IHC (such as CD8, FoxP3 and myeloid markers as appropriate).
Measured: Baseline and approximately after 3 cycles of treatment and at disease progression; cycle = 28 days
PK parameters (Eg. TMax) of EGF816
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of trametinib
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameter (Eg. TMax) of PDR001
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of canakinumab
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of CJM112
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Presence and/or concentration of anti-canakinumab antibodies.
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Presence and/or concentration of anti-CJM112 antibodies.
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measured: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2016 (estimated)
- Study start23 Aug 2016
- Primary completion17 Mar 2021
- Study completion17 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - AdenocarcinomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 283 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
- NCT02900664
- Sponsor's protocol ID
- CPDR001X2103
- Other IDs
- 2016-000633-49, 2016
- Status last verified
- Mar 2022
- First submitted
- 17 May 2016
- Last updated
- 29 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib, Open-label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacodynamics (PD) of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
- ClinicalTrials.gov ID
- NCT02900664
- Acronym / sponsor ID
- CPDR001X2103
- Keywords
- CRC, TNBC, NSCLC (adenocarcinoma), Immunomodulation, Biomarkers, Bayesian logistic regression model, PDR001, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 283 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Aug 2016 (actual)
- Primary completion
- 17 Mar 2021 (actual)
- Study completion
- 17 Mar 2021 (actual)
- First posted
- 14 Sep 2016 (estimated)
- Results
- Not posted in the source record
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 was to combine the PDR001 checkpoint inhibitor with each of four agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations.
Detailed description
This was a Phase Ib, multi-center, open-label study, to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 in combination with canakinumab, CJM112, trametinib and EGF816 and single agent (s.a.) canakinumab in subjects with Triple Negative Breast Cancer (TNBC), Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC). The study comprised a dose escalation part for combination treatments only, followed by a dose expansion part.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 23
| Arm | Type | Receives |
|---|---|---|
| PDR + ACZ 100mg Q8W | Experimental | Biological: PDR001, Biological: ACZ885PDR + ACZ 100mg Q8W |
| PDR + ACZ 300mg Q8W | Experimental | Biological: PDR001, Biological: ACZ885PDR + ACZ 300mg Q8W |
| PDR + ACZ RDE TNBC | Experimental | Biological: PDR001, Biological: ACZ885PDR + ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC) |
| PDR + ACZ RDE NSCLC | Experimental | Biological: PDR001, Biological: ACZ885PDR + ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC) |
| PDR + ACZ RDE CRC | Experimental | Biological: PDR001, Biological: ACZ885PDR + ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC) |
| PDR + CJM 25mg Q4W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 25mg Q4W |
| PDR + CJM 75mg Q4W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 75mg Q4W |
| PDR + CJM 225mg Q4W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 225mg Q4W |
| PDR + CJM 450mg Q4W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 450mg Q4W |
| PDR + CJM 450mg Q2W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 450mg Q2W |
| PDR + CJM 900mg Q4W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 900mg Q4W |
| PDR + CJM 900mg Q2W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 900mg Q2W |
| PDR + CJM 1200mg Q4W | Experimental | Biological: PDR001, Biological: CJM112PDR + CJM 1200mg Q4W |
| PDR + TMT 0.5mg QD | Experimental | Biological: PDR001, Drug: TMT212PDR + TMT 0.5mg QD |
| PDR + TMT 1mg QD | Experimental | Biological: PDR001, Drug: TMT212PDR + TMT 1mg QD |
| PDR + TMT 1mg QD, 3 Weeks on/1 Week off | Experimental | Biological: PDR001, Drug: TMT212PDR + TMT 1mg QD, 3 Weeks on/1 Week off |
| PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off | Experimental | Biological: PDR001, Drug: TMT212PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off |
| PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off | Experimental | Biological: PDR001, Drug: TMT212PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off |
| PDR + EGF816 25mg QD | Experimental | Drug: EGF816PDR + EGF816 25mg QD |
| PDR + EGF816 50mg QD | Experimental | Drug: EGF816PDR + EGF816 50mg QD |
| s.a. ACZ RDE TNBC | Experimental | Biological: ACZ885Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC) |
| s.a. ACZ RDE NSCLC | Experimental | Biological: ACZ885Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC) |
| s.a. ACZ RDE CRC | Experimental | Biological: ACZ885Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available.
- Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry)
- Non-small cell lung cancer (NSCLC) (adenocarcinoma)
- Triple Negative Breast Cancer (TNBC) (D
- ECOG Performance Status ≤ 2
Key exclusion criteria (39 listed)
- 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 severe hypersensitivity reactions to other monoclonal antibodies.
- Out of range laboratory values for measures of hepatic and renal function, electrolytes and blood counts
- Impaired cardiac function or clinically significant cardiac disease.
- Patients with active, known or suspected autoimmune disease.
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 |
|---|---|---|
| PDR001Also: Spartalizumab/PDR001Powder for solution for infusion | Biological | PDR + ACZ 100mg Q8W, PDR + ACZ 300mg Q8W, PDR + ACZ RDE CRC, PDR + ACZ RDE NSCLC, PDR + ACZ RDE TNBC, PDR + CJM 1200mg Q4W, PDR + CJM 225mg Q4W, PDR + CJM 25mg Q4W, PDR + CJM 450mg Q2W, PDR + CJM 450mg Q4W, PDR + CJM 75mg Q4W, PDR + CJM 900mg Q2W, PDR + CJM 900mg Q4W, PDR + TMT 0.5mg QD, PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off, PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off, PDR + TMT 1mg QD, PDR + TMT 1mg QD, 3 Weeks on/1 Week off |
| ACZ885Also: canakinumabSolution for injection | Biological | PDR + ACZ 100mg Q8W, PDR + ACZ 300mg Q8W, PDR + ACZ RDE CRC, PDR + ACZ RDE NSCLC, PDR + ACZ RDE TNBC, s.a. ACZ RDE CRC, s.a. ACZ RDE NSCLC, s.a. ACZ RDE TNBC |
| CJM112Solution for infusion | Biological | PDR + CJM 1200mg Q4W, PDR + CJM 225mg Q4W, PDR + CJM 25mg Q4W, PDR + CJM 450mg Q2W, PDR + CJM 450mg Q4W, PDR + CJM 75mg Q4W, PDR + CJM 900mg Q2W, PDR + CJM 900mg Q4W |
| TMT212Also: trametinibTablets | Drug | PDR + TMT 0.5mg QD, PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off, PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off, PDR + TMT 1mg QD, PDR + TMT 1mg QD, 3 Weeks on/1 Week off |
| EGF816Also: NazartinibTablets | Drug | PDR + EGF816 25mg QD, PDR + EGF816 50mg QD |
Primary outcome
Frequency of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Time frame: Throughout the study at every visit, an average of 1 year
Changes between baseline and post-baseline laboratory parameters and vital signs.
Time frame: Baseline and throughout the study at every visit, an average of 1 year
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
Time frame: During the first two cycles; Cycle = 28 days
Frequency of dose interruptions
Time frame: Throughout the study at every visit, an average of 1 year
Dose intensities
Time frame: Throughout the study at every visit, an average of 1 year
Severity of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Time frame: Throughout the study at every visit, an average of 1 year
Frequency of dose reductions
Time frame: Throughout the study at every visit, an average of 1 year
16 secondary outcomes
Key secondary: Histopathology of tumor infiltrating lymphocytes (TILs)
Time frame: Baseline and approximately after 2 cycles of treatment and at disease progression; Cycle = 28 days
Changes from baseline in electrocardiogram (ECG) parameters
Time frame: Baseline and end of treatment, an average of 1 year
Best overall response (BOR)
Time frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Progression free survival (PFS) per irRC and RECIST v1.1
Time frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Treatment Free Survival (TFS)
Time frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Presence and/or concentration of anti-PDR001 antibodies.
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Serum concentration of PDR001, canakinumab, CJM112
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Plasma concentrations of trametinib and EGF816
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Key secondary: Histopathology of myeloid cell infiltrate by IHC (such as CD8, FoxP3 and myeloid markers as appropriate).
Time frame: Baseline and approximately after 3 cycles of treatment and at disease progression; cycle = 28 days
PK parameters (Eg. TMax) of EGF816
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of trametinib
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameter (Eg. TMax) of PDR001
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of canakinumab
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of CJM112
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Presence and/or concentration of anti-canakinumab antibodies.
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Presence and/or concentration of anti-CJM112 antibodies.
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2022.
- Results for CPDR001X2103 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingObservational study
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
Solid Tumor, Adult, Colorectal Cancer
Active, not recruitingPhase 1
A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers
Carcinoma, Non-Small-Cell Lung, Cutaneous Melanoma
Active, not recruitingPhase 1
Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy
Adult Solid Neoplasm, Bladder Carcinoma
RecruitingPhase 1/2
A Study to Evaluate ARV-6723 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors
Advanced Solid Tumor
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
23 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PDR001, ACZ885 and CJM112 in people with Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma, run by Novartis Pharmaceuticals at 23 sites in 9 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 9 inclusion and 39 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 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, France, Spain, Belgium, Canada and 4 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Frequency of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety (time frame: Throughout the study at every visit, an average of 1 year). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Mar 2022.