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.
Catherine A. Shu, Kōichi Goto, Yuichiro Ohe, Benjamin Besse, Se‐Hoon Lee, Yongsheng Wang, Frank Griesinger, James Chih‐Hsin Yang, Enriqueta Felip, Rachel E. Sanborn, Reyes Bernabe, Joshua C. Curtin, Jun Chen, Janine Mahoney, Leonardo Trani, Joshua Bauml, Roland E. Knoblauch, Meena Thayu, Byoung Chul Cho
Abstract
9006 Background: Initial results with the amivantamab (ami) and lazertinib (laz) regimen showed encouraging efficacy in patients (pts) whose disease progressed after standard-of-care osimertinib (osi) and platinum-based chemotherapy (pt-chemo; Shu Ann Oncol 2021; 32:S949-1039; 1193MO). We present updated results of this population (Cohort A) from the CHRYSALIS-2 study (NCT04077463). Methods: Cohort A evaluated ami and laz in pts with EGFR exon 19 deletion or L858R NSCLC whose disease progressed on 1st/2nd-line osi followed by pt-chemo as last line of therapy (target population, n=106) and among a more heavily-pretreated population (n=56) whose disease progressed after osi and pt-chemo ± other therapies without regard to number and sequence of these therapies. Pts received 1050 mg IV ami (1400 mg, ≥80 kg) + 240 mg oral laz. Investigator (INV)- and blinded independent central review (BICR)-assessed response per RECIST v1.1 is reported for efficacy-evaluable pts, defined as pts who initiated study treatment on or before 17 Mar 2021, allowing for ≥6 mo of follow-up for response durability. Results: As of 6 Nov 2021, 162 pts were enrolled in Cohort A (median 62 y, 65% women, 61% Asian, median 3 [range, 2–14] prior lines). Median time between last osi treatment to first dose of ami + laz was 6.3 mo and 2.0 mo for the target and heavily-pretreated populations, respectively. Of 50 efficacy-evaluable pts in the target population, the overall response rate (ORR) by BICR was 36% (95% CI, 23–51), with 1 complete response (CR) and 17 partial responses (PRs), and the clinical benefit rate (CBR) was 58% (95% CI, 43–72); full results for all enrolled pts will be reported at the meeting. Median duration of response (mDOR) was not reached based on BICR. At a median follow-up of 8.3 mo, 7 responders (39%) have achieved a DOR lasting ≥6 mo by BICR. INV-assessed responses were consistent with BICR. Of 56 efficacy-evaluable pts in the heavily-pretreated population (8.7-mo median follow-up), ORR by INV was 29% (95% CI, 17–42), with 1 CR and 15 PRs. CBR was 55% (95% CI, 42–69) and mDOR was 8.6 mo (95% CI, 4.2–NR). BICR results are pending. Preliminary evidence of CNS antitumor activity was reported among 8 pts with baseline brain lesions (7 non-target, 1 target) who had not received radiation within 1 year prior to study enrollment. Most frequent adverse events (AE) were infusion-related reaction (65%), paronychia (49%), rash (41%), and stomatitis (39%). Most common grade ≥3 treatment-related AEs (TRAEs) were infusion-related reactions (7%), acneiform dermatitis (5%), and hypoalbuminemia (4%). TRAEs leading to discontinuation of either or both ami and laz occurred in 12% and 7%, respectively. Conclusions: Among an unselected population that has exhausted SOC osi and pt-chemo, ami and laz demonstrates encouraging antitumor activity with a manageable safety profile. Clinical trial information: NCT04077463.