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

Sponsor

Checkpoint Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04786964

Collaborator

(none)

560

Enrollment

Locations

Arms

47.8

Anticipated Duration (Months)

25.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Non-squamous Non Small Cell Lung Cancer	Drug: Cosibelimab Drug: Cisplatin Drug: Carboplatin Drug: Pemetrexed Dietary Supplement: Folic acid 350-1000 μg Dietary Supplement: Vitamin B12 1000 μg Drug: Dexamethasone 4mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

560 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 8, 2021

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Cosibelimab IV infusion Drug: Cisplatin IV infusion Drug: Carboplatin IV infusion Drug: Pemetrexed IV infusion Dietary Supplement: 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. 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. Drug: Dexamethasone 4mg For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.
Active Comparator: 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.	Drug: Cisplatin IV infusion Drug: Carboplatin IV infusion Drug: Pemetrexed IV infusion Dietary Supplement: 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. 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. Drug: Dexamethasone 4mg For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Arm

Intervention/Treatment

Experimental: 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.

Drug: Cosibelimab

IV infusion

Drug: Cisplatin

IV infusion

Drug: Carboplatin

IV infusion

Drug: Pemetrexed

IV infusion

Dietary Supplement: 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.

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.

Drug: Dexamethasone 4mg

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

Active Comparator: 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.

Drug: Cisplatin

IV infusion

Drug: Carboplatin

IV infusion

Drug: Pemetrexed

IV infusion

Dietary Supplement: Folic acid 350-1000 μg

Dietary Supplement: Vitamin B12 1000 μg

Drug: Dexamethasone 4mg

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

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [Approximately 3 years.]
Defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Progression-Free Survival (PFS) [Approximately 3 years.]
Defined as the time from randomization until disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Objective response rate (ORR) [Approximately 3 years.]
Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1
Duration of response (DOR) [Approximately 3 years.]
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.
Number of Participants Who Experienced an Adverse Event (AE) [Approximately 3 years.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Research Site	Vitória	Brazil
2	Research Site	Tbilisi	Georgia
3	Research Site	Kota Bharu	Malaysia
4	Research Site	Wellington	New Zealand
5	Research Site	Lima	Peru
6	Research Site	Arkhangel'sk	Russian Federation
7	Research Site	Chelyabinsk	Russian Federation
8	Research Site	Kaliningrad	Russian Federation
9	Research Site	Kazan	Russian Federation
10	Research Site	Kursk	Russian Federation
11	Research Site	Kuzmolovskiy	Russian Federation
12	Research Site	Moscow	Russian Federation
13	Research Site	Nizhny Novgorod	Russian Federation
14	Research Site	Novosibirsk	Russian Federation
15	Research Site	Omsk	Russian Federation
16	Research Site	Saint Petersburg	Russian Federation
17	Research Site	Samara	Russian Federation
18	Research Site	Sochi	Russian Federation
19	Research Site	Tomsk	Russian Federation
20	Research Site	Volgograd	Russian Federation
21	Research Site	Pretoria	South Africa
22	Research Site	Chiang Mai	Thailand