Dr. Spira Discusses CHRYSALIS-2 Research Updates

Alexander Spira, MD, PhD, FACP, FASCO, of the Virginia Cancer Specialists Research Institute, joined Lung Cancers Today to share data from cohort C of CHRYSALIS-2 that was presented at the European Lung Cancer Congress 2025.

CHRYSALIS-2 compares amivantamab plus lazertinib with EGFR tyrosine kinase inhibitor (TKI) monotherapy. Cohort C includes patients with non-small cell lung cancer (NSCLC) who are harboring atypical EGFR mutations.

Dr. Spira explained why it was critical to evaluate the combination treatment in patients with atypical EGFR mutations, noting that these patients typically don’t fare as well on EGFR-directed TKIs.

“There’s a lot of reasons that go into why these patients may do worse with the currently approved drugs,” Dr. Spira explained. “We don’t fully understand, but I suspect it’s because it’s a harder disease to treat and the current standard TKIs don’t work as well.”

The analysis compared outcomes with amivantamab plus lazertinib in cohort C with retrospective data from a matched real-world cohort of 69 patients with atypical EGFR-mutated advanced NSCLC, receiving physician-selected EGFR TKIs as a first-line treatment. Dr. Spira explained that the most common physician-selected TKIs were osimertinib (49%) and afatinib (41%).

“The overall survival was significantly longer in patients who received [amivantamab plus lazertinib],” he said.

The 24-month OS rate for patients receiving amivantamab plus lazertinib was 77%, compared with 47% among patients receiving EGFR TKIs. The median OS was not estimable.

“Based upon this, the majority of the endpoints that we’re looking at, which is overall survival, as well as two-year progression-free survival and time to discontinuation, were higher with amivantamab and lazertinib,” he said.

The study investigators concluded that first-line amivantamab plus lazertinib “significantly improved survival outcomes compared to EGFR TKI monotherapy in the real-world setting.”

Dr. Spira explained the potential next steps and his hopes for the future of treatment and research in this setting.

“I think it would be great to see a randomized study, hopefully more anecdotal data,” he concluded. “There’s some hope that this may be able to get on [National Comprehensive Cancer Network] guidelines where you can start using these drugs. Honestly, there are a lot of exciting drugs. We’ve really advanced the field in the EGFR space with multiple drugs and multiple different EGFR mutations, so it’s great for patients and it’s why we all do clinical research.”