Study of Pemetrexed+Platinum Chemotherapy With or Without Cosibelimab in First Line Metastatic Non-squamous NSCLC

NCT ID: NCT04786964

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-08
• Study Completion Date: 2023-12-30

Brief Summary

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.

Detailed Description

CK-301-301 is a Phase 3, open-label, multicenter, randomized, active-controlled study of the safety and efficacy of IV administered cosibelimab 1200 mg Q3W in combination with platinum/pemetrexed chemotherapy versus chemotherapy alone in subjects with NSCLC who have not previously received systemic therapy for advanced disease and in whom epidermal growth factor receptor-directed therapy or anaplastic lymphoma kinase-directed therapy was not indicated. Subjects were randomized 2:1 to receive cosibelimab 1200 mg in combination with pemetrexed and platinum therapy, or pemetrexed and platinum therapy alone. Subjects were stratified by smoking status (never versus former/current), cisplatin vs carboplatin, and PD-L1 status (Tumor Proportion Score [TPS] < 1% vs 1-49% vs ≥ 50%) prior to randomization. Subjects with unevaluable PD-L1 status were included with the TPS < 1% group.

Conditions

Metastatic Non-squamous Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cosibelimab

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.

Group Type: EXPERIMENTAL

Cosibelimab

Intervention Type: DRUG

IV infusion

Cisplatin

Intervention Type: DRUG

IV infusion

Carboplatin

Intervention Type: DRUG

IV infusion

Pemetrexed

Intervention Type: DRUG

IV infusion

Folic acid 350-1000 μg

Intervention Type: DIETARY_SUPPLEMENT

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.

Vitamin B12 1000 μg

Intervention Type: DIETARY_SUPPLEMENT

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.

Dexamethasone 4mg

Intervention Type: DRUG

For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Control

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.

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

IV infusion

Carboplatin

Intervention Type: DRUG

IV infusion

Pemetrexed

Intervention Type: DRUG

IV infusion

Folic acid 350-1000 μg

Intervention Type: DIETARY_SUPPLEMENT

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.

Vitamin B12 1000 μg

Intervention Type: DIETARY_SUPPLEMENT

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.

Dexamethasone 4mg

Intervention Type: DRUG

For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Interventions

Cosibelimab

IV infusion

Intervention Type: DRUG

Cisplatin

IV infusion

Intervention Type: DRUG

Carboplatin

IV infusion

Intervention Type: DRUG

Pemetrexed

IV infusion

Intervention Type: DRUG

Folic acid 350-1000 μg

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.

Intervention Type: DIETARY_SUPPLEMENT

Vitamin B12 1000 μg

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.

Intervention Type: DIETARY_SUPPLEMENT

Dexamethasone 4mg

For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Checkpoint Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Vitória, , Brazil

Research Site

Tbilisi, , Georgia

Research Site

Kota Bharu, , Malaysia

Research Site

Wellington, , New Zealand

Research Site

Lima, , Peru

Research Site

Arkhangelsk, , Russia

Research Site

Chelyabinsk, , Russia

Research Site

Kaliningrad, , Russia

Research Site

Kazan', , Russia

Research Site

Kursk, , Russia

Research Site

Kuzmolovskiy, , Russia

Research Site

Moscow, , Russia

Research Site

Nizhny Novgorod, , Russia

Research Site

Novosibirsk, , Russia

Research Site

Omsk, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Samara, , Russia

Research Site

Sochi, , Russia

Research Site

Tomsk, , Russia

Research Site

Volgograd, , Russia

Research Site

Pretoria, , South Africa

Research Site

Chiang Mai, , Thailand

Countries

Brazil; Georgia; Malaysia; New Zealand; Peru; Russia; South Africa; Thailand

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CK-301-301

Identifier Type: -

Identifier Source: org_study_id