1193MO - Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): Preliminary results from CHRYSALIS-2

Background

The combination of amivantamab (ami), an epidermal growth factor receptor (EGFR)-MET bispecific antibody, with the 3^rd-generation tyrosine kinase inhibitor lazertinib (laz), yielded a 36% overall response rate (ORR) in the post-osimertinib (osi), chemotherapy-naïve setting (Cho Ann Oncol 2020;31:S813, Oral 1258). The activity of ami + laz after progression on both osi and platinum doublet chemotherapy is unknown.

Methods

CHRYSALIS-2 (NCT04077463) is an ongoing open-label study that includes a single-arm cohort (Cohort A) examining ami + laz in patients (pts) with EGFR Exon19del or L858R NSCLC whose disease progressed after standard of care osi and platinum chemotherapy (3^rd / 4^th line; “target” population) and in more heavily-pretreated (5^th line +) pts. Pts received the established recommended combination dose of 1050 mg IV ami (1400 mg, ≥80 kg) + 240 mg oral laz. Investigator-assessed response per RECIST v1.1 is reported for pts with ≥2 post-baseline disease assessments.

Results

As of 19 Apr 2021, 116 pts were enrolled in Cohort A (median 63 y, 68% women, 60% Asian, median of 3 [range, 2–14] prior lines), with 59 in the target and 57 in the heavily-pretreated populations. Of 28 response-evaluable pts in the target population, 12 (43% [95% CI, 24–63]) reported partial response (PR) as best response; of the 12 responses, 9 were confirmed (3 pending), for an overall response rate (ORR) of 32% (95% CI, 16–52). Of 45 pts in the heavily-pretreated population, 7 reported best response of PR, of which 6 were confirmed (1 pending), for an ORR of 13% (95% CI, 5–27). At 3.7-mo median follow-up, 17 pts in the target population remain on treatment: 10 with PR (3 pending confirmation) and 7 with stable disease. The safety profile for Cohort A was consistent with previously reported experience with ami + laz at the recommended combination dose, and no new safety signals were identified.

Conclusions

Ami + laz is showing encouraging early activity in a population that progressed on both standard of care osi and platinum chemotherapy. Activity is consistent with the post-osi population, suggesting intervening chemotherapy does not impact ami + laz activity.

Clinical trial identification

NCT04077463.

Editorial acknowledgement

Medical writing assistance was funded by Janssen Global Services, LLC. and provided by Tracy T. Cao, PhD (Janssen Global Services, LLC.).

Legal entity responsible for the study

Janssen.

Funding

Janssen.

Disclosure

C.A. Shu: Financial Interests, Personal, Advisory Board: Genentech, AstraZeneca, Janssen, Mirati. K. Goto: Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin; Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Ono, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Financial Interests, Personal, Research Grant: AstraZeneca, Chugai, Lilly, Ono, BMS, Kyorin, Dainippon Sumitomo, Pfizer, Taiho, Novartis, Ignyta, Takeda, Kissei, Daiichi Sankyo, Janssen, Loxo. B. Besse: Financial Interests, Institutional, Research Grant: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE Immunotherapeutics, Pfizer, Roche-Genentech. K. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Johnson & Johnson, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim, AZD; Financial Interests, Personal, Funding: AstraZeneca, MSD Oncology. F. Griesinger: Financial Interests, Personal, Other, honoraria: Roche/Genentech, Boehringer Ingelheim, Pfizer, AbbVie. MSD, Bristol Myers Squibb, Ipsen, Novartis, AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche/Genentech, Pfizer, Boehringer Ingelheim, MSD, Bristol Myers Squibb, Celgene, Takeda, AbbVie, Novartis, Bayer, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Celgene, Lilly, Novartis, Pfizer, Roche, Takeda. J.C. Yang: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, Lilly, MSD Oncology, Merck Serono, Celgene, Astellas Pharma, Bayer, Pfizer, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim, AstraZeneca, Yuhan, Hansoh, Blueprint; Financial Interests, Personal, Other, travel, accommodation, expenses: Pfizer; Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim, Roche, MSD, AstraZeneca, Novartis, Bristol Myers Squibb, Ono Pharmaceuticals, Takeda, Lilly, Pfizer. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Medical Trends, Merck Sharp & Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health, Take; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Peervoice, Pfizer, Springer, Touch Medical; Financial Interests, Personal, Member of the Board of Directors: Grífols. R.E. Sanborn: Financial Interests, Personal, Advisory Role: Genentech/Roche, AstraZeneca, EMD Serono, Blueprint Medicines, Daiichi Sankyo/Lilly, Janssen Oncology; Financial Interests, Personal, Other, travel, accommodation, expenses: AstraZeneca; Financial Interests, Personal, Other, honoraria: AstraZeneca, Amgen; Financial Interests, Institutional, Funding: Bristol Myers Squibb, MedImmune; Financial Interests, Personal, Funding: Merck, AstraZeneca. R. Bernabe Caro: Financial Interests, Personal, Invited Speaker: Roche, Astra, BMS, Pfizer; Financial Interests, Personal, Advisory Board: Astra, BMS, Roche; Financial Interests, Personal, Research Grant: Roche. J.M. Bauml: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck, AstraZeneca, Genentech, Celgene, Boehringer Ingelheim, Guardant Health, Takeda, Novartis, Janssen, Ayala Pharmaceuticals, Regeneron, Inivata, Novartis, Foundation Medicine; Financial Interests, Institutional, Funding: Merck, Carevive Systems, Novartis, Incyte, Bayer, Janssen, AstraZeneca, Takeda, Amgen, Pfizer, Mirati Therapeutics. J. Chen: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson. E. Fennema: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Mahoney: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. L. Trani: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Thayu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B.C. Cho: Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Non-Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. All other authors have declared no conflicts of interest.