Abstract 433P
Background
This is a two-part, dose escalation and dose expansion phase Ib/II study evaluating the safety, tolerability, and preliminary efficacy of regorafenib plus toripalimab, a PD-1 mAb for patients with pMMR/MSS metastatic colorectal cancer (mCRC) who had failed ≥ 2 previous lines of chemotherapy or were intolerant to prior systemic chemotherapy.
Methods
During dose escalation, the planned dosing cohorts were 80mg, 120mg, or 160mg regorafenib [po, qd (D1-D21), q4w] plus toripalimab (3 mg/kg, iv, d1 and d15, q4w), using a mTPI design with target toxicity probability of 30%. The primary objective during dose escalation phase was MTD. During dose-expansion phase, the primary endpoint was ORR, and secondary endpoints included safety, DCR, PFS, and OS.
Results
Twelve mCRC patients were enrolled during dose escalation. Three DLTs (2 grade 3 hand-food syndrome (HFS), and 1 grade 3 transaminase elevation) occurred in 3 (100%) patients in the 120 mg regorafenib cohort. One DLT (grade 3 HFS) occurred in 9 (11.1%) patients in the 80mg regorafenib cohort. 80mg regorafenib plus 3mg/kg toripalimab was determined to be the recommended dose for the dose expansion cohort of 30 patients. As of May 12th, 2020, the ORR was 13.9% (5/36), and the DCR was 36.1% (13/36). The median PFS was 3.0 months and median OS was not reached. 95.2% patients had at least 1 TRAE and 42.9% patients had at least 1 grade 3 TRAE. The most common grade 3 TRAEs included HFS (14.3%) and impaired liver function (7.1%). No grade 4 or 5 TRAEs occurred.
Conclusions
The combination of 80mg regorafenib plus 3mg/kg toripalimab was determined to be the MTD for this study. A subset of unselected pMMR/MSS mCRC patients may benefit from this treatment. An ongoing exploratory analysis aims to provide additional insights.
Clinical trial identification
NCT03946917.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Shanghai Junshi Bioscience Co.
Disclosure
All authors have declared no conflicts of interest.