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.
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.
Janssen R&D.
Janssen R&D.
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.