Dr. Girard Shares Insights From the COCOON Trial

Nicolas Girard, MD, PhD, of Institut Curie in Paris, France, joined Lung Cancers Today to share key insights from the COCOON trial, which is being presented at the 2025 European Lung Cancer Congress (ELCC).

The study is evaluating regimens for the prevention of moderate to severe dermatologic adverse events (DAEs) experienced by patients receiving amivantamab plus lazertinib as a treatment for EGFR-mutated advanced non–small cell lung cancer (aNSCLC).

Dr. Girard explained that DAEs, such as rash and paronychia, are typically “treated reactively.” However, the phase 2 COCOON trial is exploring a prophylactic strategy targeting skin- and nail-related adverse events to help patients tolerate a longer duration of treatment.

“At this first interim analysis, 138 participants received either a prophylactic dermatologic regimen with widely available agents, including doxycycline for the first 12 weeks, clindamycin lotion on the scalp, ceramide-based moisture on the body and scalp, and chlorhexidine for the nails versus the standard of care, which is often reactive treatment of the adverse events when they occur,” he said.

Dr. Girard highlighted that the COCOON trial met its primary end point, which was incidence of grade 2 or higher DAEs of interest by week 12. The trial demonstrated a 50% reduction in the incidence of grade 2 or higher DAEs compared with the standard of care (39% vs 76%; odds ratio, 0.19; 95% CI, 0.09-0.40; P<0.0001). Reductions were also revealed across different categories of DAEs, with patients reporting a 65% reduction in body rash, a 70% reduction in scalp-related adverse events, and a 25% reduction in paronychia.

Furthermore, in the intervention group, which received enhanced dermatologic management, 43 of 70 patients did not have grade 2 or higher DAEs by week 12 versus 16 of 68 patients in the standard-of-care group.

“We also have a 2-fold reduction in grade 3 side effects,” he emphasized. “We have a lower rate of treatment dose modification and treatment discontinuation. We had also seen additional data [on preventing] the infusion-related reaction with dexamethasone given for 3 days before the first injection of amivantamab. We know that VTE [venous thromboembolism] prophylaxis with anticoagulants is a recommended part of the combination for the first 4 months, and this had been implemented in COCOON with a very low rate of VTE that was actually similar in the 2 treatment arms.”

The reduction in grade 3 side effects is occurring across prespecified subgroups, such as Asian versus non-Asian and male versus female patients, Dr. Girard said. He concluded by reflecting on future directions for the trial, highlighting next steps such as analyzing the long-term benefit of enhanced dermatologic regimens for this patient population.

“Obviously, it’s a very early timepoint right now,” Dr. Girard explained. “We have a median duration of treatment of 4 months at this interim analysis. So, obviously, we need to have a little bit more follow-up to have additional data regarding the long-term benefit of the COCOON regimen versus standard of care. It’s also very important to understand what was the incrementation of additional measures in case of side effects. We have many data to analyze, as the COCOON trial is now fully enrolled with 201 patients.”