Study design
NSCLC, tumor
SECONDARY, NSCLC, TUMOR
CHRYSALIS is an ongoing, first-in-human, open-label, multicenter, dose-escalation (part 1) and dose-expansion (part 2) phase 1 study of amivantamab as monotherapy and as combination therapy in patients with advanced NSCLC (ClinicalTrials.gov identifier: Part 1 dose escalation was implemented using a 3 + 3 design. Dosing was initiated at a dose level below the RP2D of amivantamab (700 mg for body weight <80 kg and 1,050 mg for body weight ≥80 kg) in combination with the RP2D of lazertinib (240 mg) and escalated to a second dose level of 1,050 mg of amivantamab for body weight <80 kg and 1,400 mg for body weight ≥80 kg in combination with 240 mg of lazertinib. Amivantamab was administered intravenously weekly during cycle 1 (28-d cycle) and then every other week thereafter. The first dose of amivantamab was split over 2 d, with 350 mg given on cycle 1, day 1 and the remainder of the full dose given on cycle 1, day 2. Lazertinib was given orally daily. The primary objective for part 1 was to determine the RP2CD. The primary objectives for part 2 were to evaluate the safety, tolerability and anti-tumor activity (ORR) of the amivantamab and lazertinib regimen at the RP2CD. Key secondary objectives included assessment of the clinical benefit, PFS and OS of the amivantamab and lazertinib regimen, and exploratory objectives included exploration of biomarkers predictive of clinical response from blood and tumor tissue.Doses of amivantamab were administered intravenously once weekly for the first 4 weeks and then every other week for week 5 and beyond (Fig. 