Top 10 by impressions - click to view on X
CHRYSALIS-2 Excellent data with ami/lazer for the treatment of pts w atypical EGFR mutation+ NSCLC- let me say that such good results for this subset are…uncommon😉 #ASCO24
Uncommon EGFR mutations in NSCLC often fly under the radar. This is one slide showing the first-line data for uncommon EGFR mutations — from 4 trials - ACHILLES, UNICORN, KCSG-lu15-09 , and...
#CHRYSALIS-2 evaluating Ami + Laz in patients with uncommon EGFR mutations. Impressive data in front and later lines of tx @BalazsHalmosMD @EGFRResisters...
⏰NOW OUT‼️#ASCO24 Abstracts 🔥#8516 CHRYSALIS-2: Amivantamab plus lazertinib in NSCLC with atypical EGFR mutations 🎙️Prof. Byoung Chul Cho 🎯ORR 51% (95% CI, 41–61),...
@KatsuakiMaehara Yes- you saw that right! PFS a whopping 19.5 months in treatment naive patients
@KatsuakiMaehara With such good data ami/lazer here is truly leading the PACC😉
#ASCO22 @ASCO for Mutated ADVANCED #LCSM #NSCLC (EGFRm) Shu et al. present #CHRYSALIS-2, Amivantamab + Lazertinib post...
@RenoHemonc @OncoAlert good question...data for CHRYSALIS-2 in the heavily pre tx population presented by @CatherineShuMD at ASCO this year, not presented by MET...
🚨CHRYSALIS-2 by Dr. Shu: Amivantinib+Lazertinib in EGFR-mut #NSCLC ref to Osi & chemo 🔴Heavily pretreated pts ➡️ORR 33% ➡️mPFS 5.1 ➡️mOS 14.8 mo ➡️NO diff bet EGFR ex 19 or...
CHRYSALIS-2 is an open-label Phase 1/1b study evaluating amivantamab plus lazertinib in patients with EGFR-mutated NSCLC. Cohort A enrolled 162 patients with EGFR exon 19 deletion or L858R mutations whose disease had progressed on or after osimertinib and platinum-based chemotherapy. The CHRYSALIS-2 data, together with the original CHRYSALIS trial (exon 20 insertion monotherapy) and PAPILLON (first-line exon 20 insertion combo), collectively supported the development of Rybrevant (amivantamab) across EGFR-mutant NSCLC, including the exon 20 insertion population.
Open-label, two-part, Phase 1/1b study of lazertinib as monotherapy or in combination with amivantamab in patients with advanced NSCLC. Cohort A evaluated amivantamab 1050 mg IV (1400 mg if body weight >=80 kg) plus lazertinib 240 mg oral daily in EGFR exon 19 deletion or L858R patients post-osimertinib and post-platinum chemotherapy.
Adults with advanced or metastatic NSCLC harboring EGFR exon 19 deletion or L858R mutations, ECOG PS 0-1, measurable disease per RECIST v1.1, with disease progression on or after osimertinib and platinum-based chemotherapy. Median age 61.5 years; 65% female; 62% Asian; median 3 prior lines of therapy (range 2-14). 88 patients (54%) had a history of brain or CNS metastases at baseline.
Amivantamab 1050 mg IV (1400 mg for patients >=80 kg) weekly in cycle 1 then every 2 weeks in subsequent 28-day cycles, plus lazertinib 240 mg orally daily. First amivantamab dose split: 350 mg on cycle 1 day 1 and 700 mg or 1050 mg on cycle 1 day 2 depending on body weight.
Primary endpoint: investigator-assessed ORR confirmed by BICR. Secondary endpoints: duration of response (DoR), clinical benefit rate (CBR), PFS, OS, time to treatment failure, and adverse events. Exploratory: biomarker analyses using ctDNA next-generation sequencing.
In Cohort A (N=162), BICR-assessed ORR was 35% (95% CI: 27-42), with a median duration of response of 8.3 months (95% CI: 6.7-10.9) and a clinical benefit rate of 58% (95% CI: 50-66). Median PFS by BICR was 4.5 months (95% CI: 4.1-5.8) at a median follow-up of 12 months. Among 56 responders, 57% achieved a duration of response of 6 months or longer. Investigator-assessed ORR was 28% (95% CI: 22-36) with a median DoR of 8.4 months.
Median overall survival was 14.8 months (95% CI: 12.2-18.0). For context, in the original CHRYSALIS trial evaluating amivantamab monotherapy in EGFR exon 20 insertion patients post-platinum, ORR was 40% with a median DOR of 11.1 months. In the Phase 3 PAPILLON trial (first-line amivantamab + chemo for exon 20 insertions), median PFS was 11.4 months vs 6.7 months (HR 0.40; 95% CI: 0.30-0.53; p<0.0001).
TEAEs occurred in 100% of patients; grade >=3 TEAEs in 74%. Most frequent AEs: rash (81%, grade >=3: 10%), infusion-related reactions (68%, grade >=3: 9%), paronychia (52%), hypoalbuminemia (47%, grade >=3: 6%). VTE in 19% (PE 7%, DVT 6%; grade >=3 VTE: 2%). Treatment-related dose interruptions in 56%, dose reductions in 29%, discontinuation of any study agent in 15%, and discontinuation of all agents in 7%. No treatment-related grade 5 AEs were reported.
CHRYSALIS-2 Cohort A established amivantamab + lazertinib as a viable option in the heavily pretreated EGFR-mutant NSCLC setting post-osimertinib and post-chemotherapy, where treatment options are limited. For the EGFR exon 20 insertion population specifically, Rybrevant is FDA-approved both as monotherapy (post-platinum, based on CHRYSALIS) and in combination with carboplatin/pemetrexed as first-line treatment (based on PAPILLON). The subcutaneous formulation (Rybrevant Faspro, approved December 2025) and once-monthly dosing (approved February 2026) address infusion-related burden. Key clinical debates include optimal sequencing of amivantamab-based regimens and competition with mobocertinib (withdrawn) and newer exon 20 insertion-selective agents.