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.
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
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Recurrent Lung Non-Small Cell Carcinoma
Stage IV Lung Cancer AJCC v8
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05633602
Org Class
Network
Org Full Name
SWOG Cancer Research Network
Org Study Id
S2302
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Overall survival
Outcome Time Frame
From date of randomization to date of death due to any cause, assessed up to 3 years
Secondary Ids
Secondary Id
NCI-2022-09319
Secondary Id
S2302
Secondary Id
S2302
Secondary Id
U10CA180888
Secondary Outcomes
Outcome Description
Unexpected treatment-related adverse events determined by the treating physician.
Outcome Time Frame
Up to 3 years
Outcome Measure
Incidence of high-grade (>= grade 3) adverse events
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404