Long-Term CHRYSALIS Data Continues to Show Benefit in EGFRm NSCLC


In an interview with Targeted Oncology, Se-Hoon Lee, MD, PhD, discussed long-term follow-up data from the CHRYSALIS trial in patients with EGFR-mutated advanced non–small cell lung cancer.

Se-Hoon Lee, MD, PhD

Se-Hoon Lee, MD, PhD

Long-term follow-up data from the phase 1 CHRYSALIS trial (NCT02609776) of amivantamab-vmjw (Rybrevant) and lazertinib (YH25448) show that 50% of treatment-naïve patients with EGFR-mutated non–small cell lung cancer (NSCLC) remain progression-free and on treatment at a median duration of 33.5 months, according to findings presented at the 2023 ASCO Annual Meeting.

At this time point, the median duration of response (DOR), progression-free survival, and overall survival have not been reached. Additionally, no new safety signals were identified.

The first-in-human, open-label, dose-escalation, phase 1 CHRYSALIS study is assessing the combination of amivantamab with lazertinib in treatment-naïve patients with EGFR-mutated NSCLC. In previously reported findings, all 20 patients in the study reached a partial response, with an overall response rate of 100%.

In this treatment-naive cohort, patients with EGFR exon 19 deletion or L858R mutated advanced NSCLC were enrolled and given amivantamab at a dose of 1050 mg via intravenous infusion, or 1400 mg if ≥80 kg, plus 240 mg or lazertinib orally. Among the 20 patients enrolled, the median age was 62.5 years, 55% were women, all were Asian, 11 had EGFR exon 19 deletions and 9 had L858R NSCLC.

Additional long-term data showed that at the median follow-up, 10 (50%) patients were progression-free and remained on treatment. Notably, 2 (10%) patients were treated beyond progression, and the longest patient ongoing in the trial has a duration of treatment of 37.2 months and DOR of 35.7 months. Treatment-related dose interruptions occurred in 7 (35%) patients, reductions in 8 (40%), and discontinuations in 1 (5%) of either amivantamab or lazertinib. Moreover, the safety profile was consistent with prior reports.

According to Se-Hoon Lee, MD, PhD, results from the phase 3 MARIPOSA study (NCT04487080) also investigating amivantamab with lazertinib vs osimertinib vs lazertinib in patients with previously untreated, EGFR-mutated, advanced NSCLC will further provide data regarding this combination.

In an interview with Targeted OncologyTM, Lee, MD, PhD, professor in the Division of Hematology/Oncology at Samsung Medical Center, discussed long-term follow-up data from the CHRYSALIS trial in patients with EGFR-mutated advanced NSCLC.

Targeted Oncology: Can you discuss the purpose behind the long-term analysis of the CHRYSALIS trial?

Lee: The CHRYSALIS trial is [evaluating] amivantamab for treatment-naive patients with EGFR-mutated non–small cell lung cancer, as a first line treatment. Research from the study was reported in a previous academic meeting. They're objectively sponsored 80% to 100%. Of course, it's the number of patients the age, just as a leader as a trainee. The 100% response rate was fascinating, but every clinician is concerned about the long-term follow-up data.

What were the key findings to come from the long-term data of CHRYSALIS?

After nearly 3 years of follow-up for the response rate in 100% of the cohort, half of the patients remain disease-free and alive. This is [exciting] news for patients with EGFR-mutated non–small cell lung cancer. The median progression-free survival was not reached because about half of patients remain disease-free. We are waiting for the result of a phase 3 trial [MARIPOSA; NCT04487080] of amivantamab and lazertinib vs osimertinib in patients with locally advanced or metastatic non–small cell lung cancer.

Among 20 patients, 18 provided the baseline cell-free DNA blood [test]. Of 15 patients, 100% had cell-free DNA cleared on cycle3, day 1. After a median treatment duration of 3 years, some patients progressed to this combination of amivantamab and lazertinib. We also analyzed that 1 patient had PIK3CA mutations, [there was] 1 with low-level HER2 amplification, 1 with a new CCNE1 and EGFR amplification, and 1 with no new mutations detected. We can see the benefit of this regimen for the future.

How can research with amivantamab influence the future of the lung cancer space?

As we know, the median progression-free survival with an EGFR TKI is around 2 years, but this regimen could improve it to be, hopefully, over 3 years. In the meantime, we are expecting the end results of a phase 3 trial.

What unmet needs still exist in this space?

Patients have had a happy journey through the development of many new novel and effective drugs. Still, almost all patients have failed with the EGFR TKI. In the future, we are expecting and pushing for a cure or to better long-term survival, without compromising their life or quality-of-life. We are waiting for the phase 3 results of amivantamab, but we are also waiting for results from a phase 2 study.

Also, we are concerned about the toxicity issue of the combination treatment. In the near future, we are expecting that we can have a tailored set up for our patients. For example, some patients can be treated with just monotherapy with a very tolerable toxicity profile, and some patients may have an unfavorable profile where they can be treated with a combination treatment such as TKI and chemotherapy or which could improve long-term remission, even when they have a poor prognostic factors.

Lee SH, Cho BC, Han JY, et al. Amivantamab and lazertinib in treatment-naïve EGFR-mutated advanced non–small-cell lung cancer (NSCLC): Long-term follow-up and ctDNA results from CHRYSALIS. J Clin Oncol. 2023;41(suppl 16):9134. doi:10.1200/JCO.2023.41.16_suppl.9134
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