In preclinical studies, the combination of amivantamab (EGFR-MET bispecific antibody) with lazertinib demonstrates synergistic inhibition of tumor growth. We present the safety and early efficacy results of patients receiving amivantamab in combination with lazertinib in the phase 1 CHRYSALIS study (NCT02609776).
Patients with EGFR Exon 19 deletion or L858R mutation non-small cell lung cancer (NSCLC) were enrolled in this 2-part study. To identify the recommended phase 2 combination dose (RP2CD), Part 1 enrolled patients without restriction on prior therapy to evaluate escalating dose cohorts of amivantamab (700–1050 mg, iv once weekly for 28 days; biweekly thereafter) in combination with standard monotherapy dosing of lazertinib (240 mg oral daily). The ongoing Part 2 dose expansion Cohort E is evaluating preliminary efficacy, without biomarker selection, in patients progressing on osimertinib. Response was assessed by investigator per RECIST v1.1.
As of 17 March 2020, 71 patients received the combination: median age was 61 y (36–79), median prior lines was 1 (0–9). In Part 1, the RP2CD was the maximally assessed doses of 1050 mg (1400 mg, ≥80 kg) amivantamab + 240 mg lazertinib. Interim safety profile includes rash (78%), infusion related reaction (61%), paronychia (42%), stomatitis (31%), pruritus (24%), and diarrhea (14%). Majority of treatment-related AEs were grade 1–2, with grade ≥3 reported in 7%. As of 30 April 2020, in 23 Part 1 patients with measurable disease, the overall response rate (ORR) was 43.5% (95% CI, 23.2–65.5) with 10 partial responses (PRs), and 9 patients with stable disease (SD); median treatment duration was 8.2 months (0.5–10.7), with 13 patients still ongoing. In the post-osimertinib expansion Cohort E, early antitumor activity is being observed in 14/20 response-evaluable patients with 1 complete response, 7 PRs (2 pending confirmation), and 6 SD with tumor shrinkage.
Amivantamab can be combined safely with lazertinib at their respective full monotherapy doses. Encouraging preliminary activity was observed in osimertinib-relapsed disease: updated data will be presented.
Clinical trial identification
NCT02609776; submitted November 18, 2015.
Medical writing support was provided by Tracy T. Cao, PhD (Janssen Global Services, LLC) and funded by Janssen Global Services, LLC.
Legal entity responsible for the study
B.C. Cho: Advisory/Consultancy: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Yuhan, Pfizer, Lilly, Janssen, Takeda, MSD, Ono Pharmaceuticals; Speaker Bureau/Expert testimony: Novartis; Licensing/Royalties: Champions Oncology; Shareholder/Stockholder/Stock options: Theravance, Gencurix, Bridgebio Therapeutics, Novartis, Bayer, AstraZeneca, Mogam Biotechnology Research Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD; Research grant/Funding (self): Novartis, Bayer, AstraZeneca, Mogam Biotechnology Research Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD. K.H. Lee: Advisory/Consultancy: Bristol-Myers Squibb, MSD, AstraZeneca; Honoraria (self): Bristol-Myers Squibb, MSD, AstraZeneca. D-W. Kim: Travel/Accommodation/Expenses: Daiichi Sankyo, Amgen; Research grant/Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Boehringer Ingelheim. J-Y. Han: Advisory/Consultancy: MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Lilly, Novartis, Takeda, Pfizer; Honoraria (self): Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Takeda; Research grant/Funding (self): Roche, Pfizer, Ono Pharmaceutical, Takeda. A. Spira: Advisory/Consultancy, AstraZeneca/MedImmune consulting applies to my institution: Array BioPharma, Incyte, Amgen, Novartis, AstraZeneca/MedImmune; Shareholder/Stockholder/Stock options: Lilly; Honoraria (self): CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen; Research grant/Funding (institution): Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, Arch Therap; Research grant/Funding (self): LAM Therapeutics. E.B. Haura: Advisory/Consultancy: Janssen; Travel/Accommodation/Expenses: Bristol-Myers Squibb, Roche, Janssen; Research grant/Funding (institution): Janssen, Novartis, Revolution Medicines, AstraZeneca, Genentech; Research grant/Funding (self): FORMA Therapeutics, Incyte. J.K. Sabari: Advisory/Consultancy: AstraZeneca. R.E. Sanborn: Advisory/Consultancy: Amgen, Seattle Genetics, Peregrine Pharmaceuticals, ARIAD, Genentech/Roche, AstraZeneca, Celldex, AbbVie, Takeda; Travel/Accommodation/Expenses: Five Prime Therapeutics, Janssen, AstraZeneca; Honoraria (self): AstraZeneca; Research grant/Funding (institution): Bristol-Myers Squibb, MedImmune; Research grant/Funding (self): Merck. J.M. Bauml: Advisory/Consultancy: Bristol-Myers Squibb, Merck, AstraZeneca, Genentech, Celgene, Boehringer Ingelheim, Guardant Health, Takeda, Novartis, Janssen, Ayala Pharmaceuticals, Regeneron; Research grant/Funding (institution): Merck, Carevive Systems, Novartis, Incyte, Bayer, Janssen, AstraZeneca, Takeda, Amgen. J.E. Gomez: Speaker Bureau/Expert testimony: Bristol-Myers Squibb, Atara, AstraZeneca. P. Lorenzini, J.R. Infante, J. Xie, N. Haddish-Berhane, M. Thayu, R.E. Knoblauch: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. K. Park: Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim, Lilly, Hanmi, Novartis, Ono Pharmaceutical, Roche, Bristol-Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo; Speaker Bureau/Expert testimony: Boehringer Ingelheim, AZD; Research grant/Funding (self): AstraZeneca, MSD Oncology. All other authors have declared no conflicts of interest.