Phase 3 study of lung cancer regimen designed to be a model for increasing trial diversity
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Key takeaways:
- The Pragmatica-Lung study will assess a two-drug combination vs. standard treatment for advanced NSCLC.
- The trial will use streamlined eligibility criteria to enable faster and more diverse patient enrollment.
Researchers have begun enrolling patients in Pragmatica-Lung, an NCI-supported phase 3 study designed specifically to eliminate barriers to clinical trial accessibility and participation.
The trial, also known as S2302, will evaluate a two-drug combination for patients with advanced non-small cell lung cancer. It will be among the first NCI-supported trials to use a pragmatic trial design aimed at optimizing enrollment.
S2302 is part of a larger NIH and FDA initiative to increase access to clinical trials. Pragmatic trial designs include fewer and simpler eligibility criteria, with the goal of enrolling participants more quickly and generating data that are more reflective of a real-world population.
“This is a remarkable effort that is worthy of attention,” James H. Doroshow, MD, director of NCI’s division of cancer treatment and diagnosis, said during a press briefing. “It has a very good chance of changing the standard of care for a large group of [patients with NSCLC]. Whether this is a positive or negative result — whether or not it meets its projected endpoints — it is likely to change the whole thought process and paradigm for conducting large clinical trials going forward.”
Promising phase 2 results
The Pragmatica-Lung study will enroll up to 700 adults with stage 4 or recurrent NSCLC who previously underwent treatment with immune checkpoint inhibitors and chemotherapy. Participants will be randomly assigned to a combination of ramucirumab (Cyramza, Eli Lilly), a fully human monoclonal antibody and VEGFR2 antagonist, and pembrolizumab (Keytruda, Merck), a monoclonal antibody that targets PD-1, or standard treatment. The study will primarily focus on duration of survival, with enrollment expected to be complete by the end of 2025.
The trial follows promising results of S1800A, a randomized, phase 2 clinical trial performed as part of the Lung Cancer Master Protocol (Lung-MAP). Lung-MAP, the first NCI-supported lung cancer precision medicine trial, enrolled 136 patients with advanced NSCLC who had previously undergone treatment with chemotherapy and immunotherapy.
“In this phase 2 study, we found a significant improvement in overall survival — 14.5 months with ranibizumab and pembrolizumab and 11.6 months for standard of care,” Karen L. Reckamp, MD, study chair for Pragmatica-Lung and director of medical oncology at Cedars-Sinai Cancer Center, said during the press briefing. “This was with a hazard ratio of 0.69, which is thought to be very significant. However, this was a phase 2 trial and smaller than we like to see for making treatment decisions. So, moving forward, we really want to validate that improvement we saw in overall survival.”
Enhanced recruitment efforts
Reckamp discussed the trial’s pared-down eligibility criteria, which — unlike those of many other trials — fit onto one PowerPoint slide.
“We want to look at a real-world scenario, rather than looking at ideal conditions where we have a whole laundry list of eligibility criteria that would exclude many patients with NSCLC,” Reckamp said. “We want to determine whether this intervention works under usual conditions to improve overall survival in patients with advanced NSCLC vs. standard of care.”
The study’s secondary objective is to summarize reports of serious and unexpected high-grade treatment-related adverse events.
“This is an FDA registrational trial, which makes it so important,” Reckamp said. “It has the potential to be very novel and even paradigm-changing.”
NCI collaborators for the study include SWOG Cancer Research Network, which designed the trial and will lead it in conjunction with Alliance for Clinical Trials in Oncology. ECOG-ACRIN Cancer Research Group and NRG Oncology also are participating in the trial.
Reckamp said the researchers plan to use enhanced recruitment efforts, including educational materials, Spanish versions of all patient contact and consent forms, and involvement of patient advocacy organizations. The group has also consulted with Judy Johnson, MBA, a lung cancer research advocate and survivor of early-stage breast cancer.
“We will have monthly site support calls and look at the diversity of accrual,” Reckamp said. “We will continue to reach out and provide support to the high percentage of patients who come from historically underrepresented groups. We will continue to monitor the representativeness of our enrolled population throughout the trial.”
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Pragmatica-Lung Study, a streamlined model for future cancer clinical trials, begins enrolling patients (NCI press release). Published April 12, 2023. Accessed April 12, 2023.
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