Atypical epidermal growth factor receptor (EGFR) mutations spanning exons 18 to 21 account for 10–15% of cases of EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is the only EGFR tyrosine kinase inhibitor (TKI) approved to treat these mutations. The combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a 3rd generation EGFR TKI, is being evaluated in patients with atypical EGFR mutations.
CHRYSALIS-2 (NCT04077463) is an ongoing open-label study with an expansion cohort (C) examining amivantamab + lazertinib in advanced NSCLC with atypical non-exon 20 insertion EGFR mutations (eg, S768I, L861Q, G719X). Patients may have received ≤2 prior lines of therapy, which may include one 1st- or 2nd-generation EGFR TKI. Patients receive 1050 mg IV amivantamab (1400 mg for bodyweight ≥80 kg) weekly in cycle 1 and every other week thereafter + 240 mg oral lazertinib daily. Response is assessed by the investigator per RECIST v1.1.
For this interim analysis (data cutoff June 8, 2022), 40 patients were response evaluable (had ≥1 post baseline disease assessment or discontinued for any reason). The median age of the patients was 64 years, 47.5% were female, and 19/40 had prior therapy (1 prior line of therapy in 17/40 and 2 prior lines in 2/40). Exon 19 G719X mutation accounted for most of the mutations (60.0%), with many of these patients having compound mutations. A best response of partial response (PR) was observed in 60.0% (24/40). Responses were seen in both treatment naïve as well as post-afatinib treated patients. The median duration of response was not evaluable. Of the 30 patients who had ≥3 scheduled post baseline assessments or discontinued for any reason, the objective response rate was 56.7%, with 16 (53.3%) achieving a confirmed PR (median duration of response was not evaluable) and 1 (3.3%) had an unconfirmed PR. No new safety signals or concerns were identified.
Among a patient population with few treatment options, amivantamab combined with lazertinib demonstrated encouraging anti-tumor activity in a majority of patients with a tolerable safety profile.
NCT04077463.
Kristen Evaul, Katharine Fang, and Ashley Oney, Cello Health, Communications/MedErgy.
Janssen Research & Development.
Janssen Research & Development.
B.C. Cho: Financial Interests, Personal, Other, Consulting role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Invited Speaker: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Other, Personal, Other, Founder: DAAN Biotherapeutics. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. M.E. Marmarelis: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novocure, AstraZeneca, Janssen, Takeda, Bristol Myers Squibb, Ikena; Financial Interests, Personal, Other, CME talk: Blueprint Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Gilead, Merck, Portola Pharmaceuticals, Bluebird Biosciences, Novartis, Janssen, Pfizer; Financial Interests, Institutional, Invited Speaker: Janssen, AstraZeneca, Oncotelic, Eli Lilly; Financial Interests, Institutional, Research Grant: Takeda. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., DAIICHI SANKYO Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., DAIICHI SANKYO Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., KISSEI PHARMACEUTICAL CO., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., MEDICAL ＆ BIOLOGICAL LABORATORIES CO., Ltd., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. S. Lee: Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Merck; Financial Interests, Personal, Advisory Board: Merck, Roche, AstraZeneca, Pfizer. J. Neal: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Eli Lilly and Company, Calithera Biosciences, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics; Financial Interests, Institutional, Funding: Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GSK, Janssen, AbbVie; Other, Personal, Other, Honoraria: CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, HMP Education. J. Curtin: Financial Interests, Institutional, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen Research and Development; Financial Interests, Personal, Stocks/Shares: Janssen Research and Development. J. Mahoney: Financial Interests, Personal, Full or part-time Employment: Janssen R&D. L. Trani: Financial Interests, Personal, Full or part-time Employment: Janssen. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment, I am an employee of Janssen Oncology R&D and therefore received salary and long-term compensation in the form of company stocks: Janssen Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. P. Tomasini: Non-Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Takeda, BMS, BI, Novartis. All other authors have declared no conflicts of interest.