Study of Pemetrexed+Platinum Chemotherapy With or Without Cosibelimab (CK-301) in First Line Metastatic Non-squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is an efficacy and safety study of cosibelimab (CK-301) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned in a 2:1 ratio to receive cosibelimab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin). The primary hypothesis is that cosibelimab in combination with pemetrexed/platinum chemotherapy prolongs Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.

Official Title
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A Randomized, Open-Label, Phase 3 Study of Cosibelimab (CK-301) in Combination With Platinum+Pemetrexed Chemotherapy in Subjects With First-Line Metastatic Non-squamous Non-Small Cell Lung Cancer

Conditions
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Metastatic Non-squamous Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Cosibelimab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Pemetrexed
* Dietary Supplement: Folic acid 350-1000 μg
* Dietary Supplement: Vitamin B12 1000 μg
* Drug: Dexamethasone 4mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV non-squamous NSCLC. Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated. Has measurable disease. Has not received prior systemic treatment for their advanced/metastatic NSCLC. Can provide tumor tissue. Has a life expectancy of at least 3 months. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status. Has adequate organ function If female of childbearing potential, is willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. If male with a female partner(s) of child-bearing potential, must agree to use adequate contraception starting with the first dose of study medication through 180 days after the last dose of study medication and chemotherapeutic agents. Exclusion Criteria: Has predominantly squamous cell histology NSCLC. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of study medication. Before the first dose of study medication: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy (e.g., erlotinib, crizotinib, cetuximab), c) Had major surgery (<3 weeks prior to first dose). Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study medication. Completed palliative radiotherapy within 7 days of the first dose of study medication. Is expected to require any other form of antineoplastic therapy while on study. Received a live-virus vaccination within 30 days of planned start of study medication. Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis. Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb). Known sensitivity to any component of cisplatin, carboplatin or pemetrexed. Has active autoimmune disease that has required systemic treatment in past 2 years. Is on chronic systemic steroids. Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). Is unable or unwilling to take folic acid or vitamin B12 supplementation. Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. Has an active infection requiring therapy. Has known history of Human Immunodeficiency Virus (HIV). Has known active Hepatitis B or C. Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. Is a known regular user of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol). Has symptomatic ascites or pleural effusion. Has active or history of interstitial lung disease or a history of (non infectious) pneumonitis that required steroids or current pneumonitis. Has had an allogeneic tissue/solid organ transplant. Any known uncontrolled or significant cardiovascular disease. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cosibelimab<br>Participants receive cosibelimab 1200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by cosibelimab 1200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. | Drug: Cosibelimab<br>* IV infusion<br>Drug: Cisplatin<br>* IV infusion<br>Drug: Carboplatin<br>* IV infusion<br>Drug: Pemetrexed<br>* IV infusion<br>Dietary Supplement: Folic acid 350-1000 μg<br>* Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.<br>Dietary Supplement: Vitamin B12 1000 μg<br>* Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.<br>Drug: Dexamethasone 4mg<br>* For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.<br>|
| Active Comparator: Control<br>Participants receive pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pemetrexed 500 mg/m^2 IV Q3W until progression. | Drug: Cisplatin<br>* IV infusion<br>Drug: Carboplatin<br>* IV infusion<br>Drug: Pemetrexed<br>* IV infusion<br>Dietary Supplement: Folic acid 350-1000 μg<br>* Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.<br>Dietary Supplement: Vitamin B12 1000 μg<br>* Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.<br>Drug: Dexamethasone 4mg<br>* For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Defined as the time from randomization to death due to any cause. | Approximately 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Defined as the time from randomization until disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | Approximately 3 years. | 
| Objective response rate (ORR) | Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1 | Approximately 3 years. | 
| Duration of response (DOR) | Defined as the time from the earliest date of documented response until earliest date of disease progression (per RECIST v1.1) or death from any cause, whichever comes first. | Approximately 3 years. | 
| Number of Participants Who Experienced an Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a study participant administered study drug and which does not necessarily have to have a causal relationship with this study drug. | Approximately 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CK-301, Cosibelimab, Non-squamous NSCLC, Carcinoma, non-small cell lung, Antineoplastic agents, Anti-PD-L1, Metastatic, non-small cell lung cancer, nonsquamous, PD-L1, PD-1, PDL1, PD1, Lung neoplasms