Study design
tumor
ADVERSE EVENTS, MAY, TUMOR, DISEASE PROGRESSION
This was a phase 1, open-label, dose-escalation and dose-expansion study conducted from 4 May 2018 to 31 May 2021 at eight sites in Australia and one site in New Zealand. The study was approved by independent ethics committee/institutional review boards at each site, and adhered to the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent.Two parts were planned: part 1 (monotherapy dose escalation [phase 1a] and dose expansion in select tumor types [phase 1b]) and part 2 (nofazinlimab in combination with regorafenib dose escalation [part 2a] in mCRC and expansion [part 2b]) (Supplementary Fig. In part 1 phase 1b, patients received nofazinlimab at 200 mg Q3W in arms 1 and 2, and were alternately enrolled to receive nofazinlimab at 200 mg Q3W in arm 3 or 400 mg Q6W in arm 4 (In part 2a, nofazinlimab was administered intravenously at 300 mg Q4W combined with regorafenib orally at 80 mg (dose level 1) and 120 mg (dose level 2) once daily (QD) for the first 21 days of each 28-day cycle. The regorafenib label dose is 160 mg taken orally QD for the first 21 days of each 28-day cycle. Based on the regorafenib registration study results of CONCUR and CORRECT, most of grade 3/4 AEs (54% patients in 160 mg regorafenib treatment developed grade 3/4 AE) occurred in the first two cycles [The primary objectives were to evaluate the safety, tolerability, maximum tolerated dose (MTD), if any, and RP2D of nofazinlimab in part 1 phase 1a and regorafenib in combination with nofazinlimab in part 2a. The primary objective of part 1 phase 1b was to evaluate the objective response rate (ORR) of two dosing schedules of nofazinlimab in patients with selected tumor types. Secondary objectives included assessing the PK, preliminary anti-tumor activity and immunogenicity of nofazinlimab. Exploratory objectives included biomarker analyses such as PD-L1 expression.Patients could receive treatment for up to 2 years or until treatment discontinuation due to disease progression, patient withdrawal or significant adverse events (AEs) (as defined in the protocol). Patients who were still benefiting from the study drug after the completion of the main study were switched to the extension study phase.