Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results
Xiao-Li Wei1, Yang Zhang2, Hong-Yun Zhao2
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Background:
SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC).
Patients And Methods:
Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD.
Results:
In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors.
Conclusions:
SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status.
Insights
SHR7390, a MEK1/2 inhibitor, showed a manageable safety profile when combined with camrelizumab in advanced colorectal cancer patients. Preliminary antitumor activity was observed across different tumor subtypes.
Area of Science:
- Oncology
- Pharmacology
Background:
- SHR7390 is a novel, selective inhibitor targeting MEK1/2.
- Two Phase I trials investigated SHR7390 monotherapy and its combination with camrelizumab.
Purpose of the Study:
- Evaluate the tolerability, safety, and antitumor activity of SHR7390.
- Determine the maximum tolerated dose (MTD) for SHR7390 monotherapy and in combination with camrelizumab.
Main Methods:
- Accelerated titration scheme used to determine MTD.
- Patients received SHR7390 alone or with camrelizumab.
- Primary endpoints included dose-limiting toxicity (DLT) and MTD.
Main Results:
- SHR7390 monotherapy MTD was 0.75 mg; no objective responses observed.
- SHR7390 (0.5 mg) plus camrelizumab showed a manageable safety profile in colorectal cancer (CRC) patients.
- Partial responses (PR) were observed in 22.7% of CRC patients, including those with MSI-H tumors.
Conclusions:
- SHR7390 0.5 mg combined with camrelizumab demonstrated a manageable safety profile.
- Preliminary clinical activity was noted irrespective of microsatellite instability (MSI) and BRAF mutation status.
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