cancer lung carcinoma
Conditions
Interventions
Subjects will undergo screening tests and assessments to determine eligibility,
and those eligible for the study will be randomised to a treatment arm in the
following ratio: 1:1 Arm A: Induction pe
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Participants must have histologically or cytologically documented Extensive Stage Small Cell Lung Cancer (ES SCLC). Participants must present with extensive stage IV disease based on the American Joint Committee on Cancer, 7th edition guidelines. The following grades will be considered: T any, N any, M1a, or M1b, or T3-4 due to multiple lung nodules that are too extensive or tumour or nodal volume that is too large to be encompassed in a tolerable radiation plan. 2. a. Archived tumor specimens, in the form of blocks or sectioned slides, are mandatory for all participants except those participating in the separate PET tracer sub-study for whom the archived tumor specimen is optional. b. Participants taking part in the separate PET tracer sub-study must provide a fresh tumor biopsy from any disease site (primary or metastatic). Mandatory minimum of 3 cores to be processed as 2 fresh frozen and the rest as formalin fixed paraffin embedded. Refer to Section 9.8.1 and the Laboratory Manual for further details on procedures for collecting fresh tumor samples. Note: if during the attempt to collect the tumor biopsy there are safety issues and a sample may not be obtained or is not suitable for the study per protocol requirements, the participant may still be allowed to enter in the study after consultation with BMS Medical Monitor. 3. Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 or 1. 4. Participants must have at least 1 measurable lesion, measured by computed tomography (CT) or magnetic resonance imaging (MRI). This will be evaluated per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) criteria. 5. Participants must be suitable to receive a platinum-based chemotherapy regimen as per locally approved drug labels and institutional guidelines. 6. Adequate hematologic and end organ function as defined below: a. Absolute neutrophil count >= 1,500/mm3 (stable off any growth factor within 2 weeks of the first study drug administration) b. Platelets >= 100,000/mm3 (transfusion to achieve this level is not permitted within 2 weeks of the first study drug administration) c. Hemoglobin >= 9 g/dL (transfusion to achieve this level is not permitted within 2 weeks of the first study drug administration) d. White blood cells >= 2000/mm3 e. Total bilirubin 50 mL/min (using the Cockcroft-Gault formula) 7. Males and Females aged 18 years or older a. Women who are not of childbearing potential are exempt from contraceptive requirements b. Women participants must have documented proof that they are not of childbearing potential c. Women of Childbearing Potential (WOCBP) must have a negative highly sensitive urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) within 24 hours prior to the start of study treatment). An extension up to 72 hours prior to the start of study treatment is permissible in situations where results cannot be obtained within the standard 24-hour window. d. WOCBP must agree to follow instructions f
Exclusion criteria
Exclusion criteria: 1. Medical Conditions a. Women who are pregnant or breastfeeding. b. Any significant acute or chronic medical illness that would interfere with study treatment or follow-up c. Inability to undergo venepuncture and/or tolerate venous access. d. Any other sound medical, psychiatric, and/or social reason as determined by the investigator e. Participants with symptomatic brain or other central nervous system (CNS) metastases. Participants are eligible if brain or other CNS metastases are asymptomatic and do not require immediate treatment or have been adequately treated. They must have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, participants must be either off corticosteroids or on a stable or decreasing dose of = 2 peripheral sensory neuropathy at study entry. i. Participant has uncontrolled or active systemic fungal, bacterial, viral, or other infection despite appropriate anti-infective treatment, within 7 days prior to the first dose of study drug. j. Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past year or a current CD4 count 160 mm Hg or diastolic blood pressure > 100 mm Hg, despite optimal medical management. ii.) Active coronary artery disease, including unstable or newly diagnosed angina within 3 months of study enrollment. iii.) Myocardial infarction in the past 6 months. iv.) History of congenital long QT syndrome. v.) History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de pointes. vi.)Uncontrolled heart failure, defined as Class 3 or 4 by New York Heart Association functional classification. vii.) History or current diagnosis of myocarditis. l. Participants with an active, known or suspected autoimmune disease or inflammatory disorder. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trig
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To assess the safety and tolerability for participants randomized to BMS-986012 in combination with carboplatin, etoposide, and nivolumab for 4 cycles (induction) followed by BMS-986012 and nivolumab maintenance (Arm A) vs those randomized to carboplatin, etoposide, and nivolumab for 4 cycles (induction) followed by nivolumab maintenance (Arm B). 2. To compare the Progression Free Survival (PFS) as assessed by Blinded Independent Central Review (BICR) of participants treated in the combination induction and maintenance therapies of Arms A and B described above. Assessment will be based on RECIST v1.1 criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To estimate the Progression Free Survival Rate (PFSR) at 6 and 12 months in each treatment arm, based on Progression Free Survival (PFS) by RECIST v1.1 as assessed by Blinded Independent Central Review (BICR) 2. To compare PFS as assessed by investigator of participants treated in the combination induction and maintenance therapies of Arms A and B described above. 3. To estimate the PFSR at 6 and 12 months in each treatment arm based on PFS by RECIST v1.1 assessed by investigator. 4. To estimate the Objective Rate of Response (ORR), Time To Response (TTR), and Duration of Response (DOR) by RECIST v1.1 criteria by BICR and by investigator. 5. To assess Overall Survival (OS) of Arm A and Arm B and estimate Overall Survival Rate (OSR) at 12 and 24 months by treatment arm. 6. To characterize the immunogenicity of BMS-986012 in combination with carboplatin, etoposide, and nivolumab in Arm A. Tertiary / exploratory 1. To assess disease-related symptoms measured by Lung Cancer Symptom Scale. 2. To assess the bother associated with the side effects of treatment. 3. To assess associations of fuc-GM1 expression in pretreatment tumor biopsies assessed using IHC and mass spectrometry assays with anti-tumor activity measures. 4. To assess associations of PD-L1 expression (CPS) in pretreatment tumor biopsies with anti-tumor activity measures. 5. Fuc-GM1 expression on CTCs and associations with baseline fuc-GM1 expression measures; changes in CTC count during treatment (from baseline) and associations with response to treatment in each arm. 6. To explore associations with antitumuor activity measures in Arms A and B with changes in biomarkers during treatment such as the following: • NK cell-mediated ADCC gene expression • Immune cell population in blood (ie, NK cell activation) • Shed fuc-GM1 levels in plasma 7. To explore associations with anti-tumour activity measures in Arms A and B with baseline biomarkers such as the following: • Fuc-GM1 sy | — |
Countries
Netherlands
Outcome results
None listed