Grand Rounds February 24, 2023: S2302 Pragmatica-Lung: New Directions for Decreasing Burden and Increasing Inclusion in NCTN Clinical Trials (Konstantin Dragnev, MD; Karen Reckamp, MD, MS)

Posted on by Elizabeth Mccamic

Speakers

Konstantin Dragnev, MD
Professor of Medicine, Hematology/Oncology
Irene Heinz Given Professor in Pharmacology
Associate Director for Clinical ResearchPrincipal Investigator – Dartmouth Lead Academic Participating Site for NCTN
Dartmouth Cancer Center
Dartmouth Health

Karen Reckamp, MD, MS
Director, Division of Medical Oncology
Associate Director, Clinical Research
Clinical Professor, Department of Medicine
Cedars-Sinai Cancer

 

Keywords

Pragmatic Clinical Trial, Lung Cancer

 

Key Points

  • S2302 is an ongoing Phase III pragmatic clinical trial designed to reduce the burden of clinical trial participation and to promote the inclusion of all participants with non-small cell lung cancer (NSCLC).
  • S1800A was a Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for NSCLC patients previously treated with immunotherapy performed within the Lung-MAP platform. Overall survival was significantly improved with a hazard ratio of 0.69, median OS of 14.5 and 11.6 months, for pembrolizumab and ramucirumab vs. standard of care, respectively. The aim of S2302 is to validate the improvement in overall survival in S1800A.
  • Patients are eligible to participate in the S2302 if they are at least 18 years old with Stage IV or recurrent non-small cell lung cancer, need for prior treatment with one line of immunotherapy and a platinum based combination performance status between 0 and 2 and determination by the treating investigator that it is safe for the participant to receive either the investigational combination or standard of care.
  • For the standard of care arm, treatment is determined by the treating investigator and participant, with the recommendation that the choice of drug is based on NCCN guidelines and dosing administration based on the participant’s previous therapy and disease.
  • For the investigational ramucirumab plus pembrolizumab arm, the drugs are administered per FDA package insert and institutional standard in a 21-day cycle under one of the criteria for removal is met. Ramucirumab will be administered prior to pembrolizumab; participants will receive 35 cycles of pembrolizumab, and maintenance ramucirumab may continue for participants past 35 cycles until reaching discontinuation criteria.
  • Criteria for removal from treatment include progression of disease based on investigator assessment; unacceptable toxicity; and participants may withdraw from the protocol treatment at any time for any reason.
  • To reduce the burden on sites, the study has simplified data reporting by reducing time points data, reducing the number of forms that need to be submitted, and reducing the number of data elements within a form. The study does not include tissue specimen collection, image submission, or patient-reported outcome instruments. The informed consent document has been simplified and is shorter than the usual NCTN template informed consent document.

 

Discussion Themes

– What does a study champion mean in the context of this study? One network is the lead, but the trial will be available in all four U.S. networks. We have found that having an involved investigator in each network improves engagement. We are working on inclusion and making sure all of our trials have buy in across the group.

– What was the rationale for the choice of study treatments (i.e., verses other immunotherapeutic agents)? There is a strong mechanistic rationale. They are both approved and used widely in lung cancer, and combining two existing agents is logistically and clinically simpler. We got both Merck and Lily to work together in the Phase II trial, then the data from that trial that showed survival benefit led to the Phase III study. It’s been a collaboration across multiple groups and entities and the fact that a lot of people decided to work together.

–Are there any concerns that the pragmatic nature could reduce the chance of showing a benefit? When we started working on this the discussions with NCI and FDA were about stripping away eligibility, we realized the population would be less controlled than previous studies. We kept coming back to the one thing we want to know, which is the overall survival. We have a higher threshold than most because we know that these patients will be a little more variable and robust

Tags

#pctGR, @Collaboratory1