E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety, tolerability, and DLTs of BMS-986207 in combination with nivolumab plus ipilimumab in participants with 1L Stage IV NSCLC (Part 1)
To compare the PFS of BMS-986207 in combination with nivolumab plus ipilimumab (Arm A) versus nivolumab plus ipilimumab (Arm B) in participants with 1L Stage IV NSCLC expressing PD-L1 (Part 2)
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E.2.2 | Secondary objectives of the trial |
PFS of BMS-986207 in combination with nivolumab plus ipilimumab (Arm A) versus nivolumab plus ipilimumab (Arm B) in randomized participants and in subgroups defined by PD-L1 expression
Safety and tolerability of BMS-986207 in combination with nivolumab plus ipilimumab (Arm A) and nivolumab plus ipilimumab (Arm B) in participants with 1L Stage IV NSCLC (Part 2)
ORR and DOR of BMS-986207 in combination with nivolumab plus ipilimumab (Arm A) and nivolumab plus ipilimumab (Arm B) in randomized participants and in subgroups defined by PD-L1 expression
OS of BMS-986207 in combination with nivolumab plus ipilimumab (Arm A) versus nivolumab plus ipilimumab (Arm B) in randomized participants and in subgroups defined by PD-L1 expression
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males and females; ≥ 18 years of age or local age of majority. Histologically confirmed metastatic 1L Stage IV NSCLC of squamous or nonsquamous histology No prior systemic anti-cancer treatment given as primary therapy for advanced or metastatic NSCLC Measureable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Participants must have a life expectancy of at least 3 months at the time of first dose. A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor tissue obtained during screening or prior to enrollment (within 3 months of enrollment and with no intervening systemic anticancer treatment between time of acquisition and enrollment). Samples must be sent to central laboratory and confirmed to be evaluable prior to treatment assignment or randomization. Assessment of tumor-cell PD-L1 expression by immunohistochemistry must be performed by central laboratory using pre-treatment tissue sample, and results must be reported prior to randomization (Part 2).
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E.4 | Principal exclusion criteria |
Participants with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or c-ros oncogene 1 (ROS-1) mutations which are sensitive to available targeted inhibitor therapy. Participants with nonsquamous histology and unknown EGFR, ALK, or ROS-1 status are also excluded. Participants with known B-rapidly accelerated fibrosarcoma proto-oncogene (BRAF) V600E mutations that are sensitive to available targeted inhibitor therapy. Participants with unknown or indeterminate BRAF mutation status are eligible. Participants with untreated central nervous system metastases. Participants with leptomeningeal metastases (carcinomatous meningitis). Concurrent malignancy requiring treatment. Participants with an active, known, or suspected autoimmune disease. Prior treatment with anti-TIGIT, anti-PD-(L)1, anti- CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Women who are pregnant or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence of AEs meeting protocol-defined DLT criteria, AEs, TRAEs, SAEs, AEs leading to discontinuation, and deaths - PFS based on RECIST v1.1 by BICR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Incidence of AEs meeting protocol-defined DLT criteria, AEs, TRAEs, SAEs, AEs leading to discontinuation, and deaths: ~ 4years -PFS based on RECIST v1.1 by BICR ~ 25 months |
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E.5.2 | Secondary end point(s) |
-PFS based on RECIST v1.1 by BICR and Investigator’s assessment -Incidence of AEs, SAEs, AEs leading to discontinuation, and deaths -ORR and DOR based on RECIST v1.1 by BICR and Investigator’s assessment -OS
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-PFS based on RECIST v1.1 by BICR and Investigator’s assessment: ~ 25months -Incidence of AEs, SAEs, AEs leading to discontinuation, and deaths: ~ 4years -ORR and DOR based on RECIST v1.1 by BICR and Investigator’s assessment: ~25months -OS: ~30months
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Chile |
United States |
Belgium |
France |
Germany |
Italy |
Poland |
Spain |
Argentina |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 12 |