The combination of amivantamab and lazertinib, which target epidermal growth factor receptor (EGFR) by different mechanisms, continues to show encouraging results in patients with EGFR-mutant non-small cell lung cancer (NSCLC) who have run out of standard treatment options, according to updated results of the CHRYSALIS-2 study.

Catherine A. Shu, MD, of Columbia University Medical Center, New York, New York, presented the update at the 2022 ASCO Annual Meeting.

Amivantamab is a bispecific antibody targeting the extracellular domains of EGFR and MET. Lazertinib is a brain-penetrating third-generation EGFR tyrosine kinase inhibitor targeting the receptor’s catalytic domain.

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CHRYSALIS-2 has a phase 1/1b design. Initial results for the 162 patients in study Cohort A, previously reported, showed “encouraging efficacy” in this population who had exhausted standard of care treatment, having experienced progression on osimertinib and platinum-based chemotherapy.

Cohort A enrolled patients with NSCLC having an EGFR exon 19 deletion or L858R mutation. The median number of prior therapies was 3, and 41% of patients had brain metastases at baseline. The patients received 1050 mg intravenous amivantamab plus 240 mg oral lazertinib.

The overall response rate was 33%, with 1% of patients having complete responses and 32% having partial responses. After restriction to confirmed responses and addition of cases of durable stable disease, the clinical benefit rate was 57%.

Median duration of response was 9.6 months. With a median follow-up of 10 months, the median progression-free survival was 5.1 months with a median overall survival of 14.8 months.

According to Dr Shu, amivantamab and lazertinib led to durable disease control. Among 54 responders, 30 remained on treatment at the time of clinical cutoff and 27 had a duration of response of 6 months or longer.

“Among a patient [population] that has exhausted standard of care, including heavily pretreated patients, amivantamab and lazertinib demonstrated clinically significant and durable antitumor activity, without biomarker selection,” Dr Shu said. “Importantly, this represents a chemotherapy-free regimen for our patients.”

Adverse events were mostly of grade 1 and 2. About one-third (35%) of patients had dose interruptions, but fewer required dose reductions (9%) or discontinuations (7%). Overall, the safety profile was consistent with what has been previously reported with these drugs, with no new safety signals identified.

Disclosure: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Shu CA, Goto K, Ohe Y, et al. Amivantamab and lazertinib in patients with EGFR-mutant non-small cell lung (NSCLC) after progression on osimertinib and platinum-based chemotherapy: Updated results from CHRYSALIS-2. Presented at ASCO 2022; June 3-7, 2022. Abstract 9006.