Non-Chemotherapy Treatment (Ramucirumab plus Pembrolizumab) or Standard Chemotherapy for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Trial
18 Years and older, Male and Female
S2302 (primary)
S2302
NCI-2022-09319
Summary
This phase III trial compares the effect of the combination therapy with ramucirumab and pembrolizumab versus standard of care chemotherapy for the treatment of non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if combination therapy with ramucirumab and pembrolizumab could help patients with stage IV or recurrent non-small cell lung cancer live longer compared to standard chemotherapy.
Objectives
PRIMARY OBJECTIVE:
I. To compare overall survival (OS) in participants previously treated with platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC) randomized to pembrolizumab and ramucirumab versus standard of care.
SECONDARY OBJECTIVE:
I. To summarize reports of serious and unexpected high-grade (>= grade 3) treatment-related adverse events determined by the treating physician within each treatment arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive standard-of-care chemotherapy per investigator's choice based on Food and Drug Administration (FDA)-approved package insert(s).
ARM B: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on day 1 of each cycle and pembrolizumab IV over 30 minutes on day 1 for up to 35 cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of the study treatment, patients are followed up every 3 months until death or 3 years after randomization, whichever occurs first.
Eligibility
- Participants must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) which is stage IV or recurrent
- Participants must have received exactly one anti-PD-1 or anti-PD-L1 therapy for advanced disease (Stage IV or recurrent disease, or stage I-III disease in certain circumstances) outlined below. Anti-PD-1 or anti-PD-L1 therapy may have been given alone or in combination with other therapy
* For participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy for stage I-III disease
* If they experienced disease progression within (=<) 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy, this counts as the single allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease
* If they experienced disease progression more than (>) 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy, this is not considered anti-PD-1 or anti-PD-L1 therapy for advanced disease. These participants must have received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease
- Participants must have experienced disease progression (in the opinion of the treating physician) more than (>) 84 days following initiation (cycle 1 day 1) of their most recent anti-PD-1 or anti-PD-L1 therapy
- Participants who received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease, must have had a best response of stable disease, partial response or complete response (in the opinion of the treating physician) on the anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease
- Participants must have received platinum-based chemotherapy and experienced disease progression (in the opinion of the treating physician) during or after this regimen
- Participants with a known sensitizing mutation for which an Food and Drug Administration (FDA)-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 and MET sensitizing mutations), must have previously received at least one of the approved therapy(s). Prior targeted therapy for participants with targetable alterations is allowed if all other eligibility criteria are also met
- Participants must not be receiving or planning to receive another investigational therapy during study participation
- Participants must be >= 18 years old
- Participants must be able to safely receive the investigational drug combination and the investigator’s choice of standard of care regimens per the current FDA-approved package insert(s), treating investigator’s discretion, and institutional guidelines
- Participants must have Zubrod performance status of 0-2
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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