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

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ClinicalTrials.gov Identifier: NCT05633602
Recruitment Status : Recruiting
First Posted : December 1, 2022
Last Update Posted : February 8, 2024
Sponsor:
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  ICMJE November 21, 2022
First Posted Date  ICMJE December 1, 2022
Last Update Posted Date February 8, 2024
Actual Study Start Date  ICMJE March 14, 2023
Estimated Primary Completion Date March 15, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Lung Non-Small Cell Carcinoma
  • Stage IV Lung Cancer AJCC v8
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2022)
700
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 15, 2028
Estimated Primary Completion Date March 15, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05633602
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Current Responsible Party SWOG Cancer Research Network
Original Responsible Party Same as current
Current Study Sponsor  ICMJE SWOG Cancer Research Network
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Eli Lilly and Company
  • Merck Sharp & Dohme LLC
Investigators  ICMJE
Principal Investigator: Karen L Reckamp SWOG Cancer Research Network
PRS Account SWOG Cancer Research Network
Verification Date February 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP