Ramucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study

• ClinicalTrials.gov Identifier: NCT05633602
• Recruitment Status: Recruiting
• First Posted: December 1, 2022
• Last Update Posted: February 8, 2024
• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI); Eli Lilly and Company; Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): SWOG Cancer Research Network

Tracking Information

• First Submitted Date: November 21, 2022
• First Posted Date: December 1, 2022
• Last Update Posted Date: February 8, 2024
• Actual Study Start Date: March 14, 2023
• Estimated Primary Completion Date: March 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2022)

Overall survival [ Time Frame: From date of randomization to date of death due to any cause, assessed up to 3 years ]

Assessed in participants with stage IV or recurrent non-small cell lung cancer with acquired resistance to anti-PD-1 or anti-PD-L1 therapy randomized to ramucirumab and pembrolizumab or standard of care chemotherapy. Will use an intention-to-treat analysis and the comparison will be done using a stratified log-rank test. The distribution of overall survival will be estimated using the method of Kaplan-Meier and a Cox proportional hazards model will be used to estimate hazard ratios and associated 95% confidence intervals to estimate treatment effects.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 21, 2022)

Incidence of high-grade (>= grade 3) adverse events [ Time Frame: Up to 3 years ]

Unexpected treatment-related adverse events determined by the treating physician.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ramucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study
• Official Title: Pragmatica-Lung: A Prospective Randomized Study of Ramucirumab (LY3009806; NSC 749128) Plus Pembrolizumab (MK-3475; NSC 776864) Versus Standard of Care for Participants Previously Treated With Immunotherapy for Stage IV or Recurrent Non-Small Cell Lung Cancer
• Brief Summary: This phase III trial compares the effect of the combination of 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 giving ramucirumab with pembrolizumab is more effective at treating patients with stage IV or recurrent non-small cell lung cancer than standard chemotherapy.

Detailed Description

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 chemotherapy per standard of care on study.

ARM B: Patients receive ramucirumab intravenously (IV) and pembrolizumab IV on study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Recurrent Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8

Intervention

• Drug: Chemotherapy
  Receive standard of care chemotherapy
  Other Names:

  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General
• Biological: Pembrolizumab
  Given IV
  Other Names:

  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475
• Biological: Ramucirumab
  Given IV
  Other Names:

  • Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B
  • Cyramza
  • IMC-1121B
  • LY3009806

Study Arms

• Active Comparator: ARM A (standard of care chemotherapy)
  Patients receive chemotherapy per standard of care on study.
  Intervention: Drug: Chemotherapy
• Experimental: ARM B (ramucirumab, pembrolizumab)
  Patients receive ramucirumab IV and pembrolizumab IV on study.
  Interventions:

  • Biological: Pembrolizumab
  • Biological: Ramucirumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 21, 2022): 700
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 15, 2028
• Estimated Primary Completion Date: March 15, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) which is stage IV or recurrent
• Participants must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for any stage of NSCLC. Anti-PD-1 or anti-PD-L1 may have been given alone or in combination with other therapy
• 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 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 on anti-PD-1 or anti-PD-L1 therapy of stable, partial response or complete response (in the opinion of the treating physician)
• Participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy as their only line of anti-PD-1 or anti-PD-L1 therapy must have experienced disease progression within (=<) 365 days from initiation (cycle 1 day 1) of anti-PD-1 or PD-L1 therapy
• 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 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

Exclusion Criteria:

• Participants must not have received more than one line of anti-PD-1 or anti-PD-L1 for stage IV or recurrent disease
• Participants must not be receiving or planning to receive another investigational therapy during study participation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05633602
• Other Study ID Numbers: S2302; NCI-2022-09319 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S2302 ( Other Identifier: SWOG ); S2302 ( Other Identifier: CTEP ); U10CA180888 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SWOG Cancer Research Network
• Original Responsible Party: Same as current
• Current Study Sponsor: SWOG Cancer Research Network
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Eli Lilly and Company
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Karen L Reckamp; SWOG Cancer Research Network

• PRS Account: SWOG Cancer Research Network
• Verification Date: February 2024