SHR7390 represents an innovative and highly specific inhibitor targeting MEK1/2. The findings presented here stem from a pair of early-stage clinical studies aimed at assessing the safety, tolerability, and potential anticancer effects of SHR7390 used alone in cases of progressed solid malignancies, as well as in conjunction with camrelizumab for individuals with heavily pretreated advanced or metastatic colorectal cancer (CRC). Participants were administered SHR7390 either as a single agent or alongside a standard dose of camrelizumab (200 mg intravenously biweekly) through an accelerated dose-escalation approach to identify the maximum tolerated dose (MTD). A suitable dose for further evaluation was selected based on tolerability and safety observed during escalation. Key objectives focused on dose-limiting toxicities (DLTs) and determination of the MTD. In the study evaluating SHR7390 alone, a total of 16 individuals were included. DLTs emerged at the 1.0 mg level, leading to an MTD of 0.75 mg. Severe (grade ≥3) treatment-emergent adverse events linked to the drug occurred in 4 cases (25.0%). None of the participants experienced an objective tumor response. For the combination study involving SHR7390 and camrelizumab, 22 CRC patients were recruited. A single DLT was noted at the 0.5 mg dose, with no MTD established. Serious (grade ≥3) drug-related adverse events affected 8 patients (36.4%), predominantly skin rash (observed in 4 individuals). One fatal (grade 5) event involving elevated intracranial pressure was recorded. Partial responses were seen in 5 patients (22.7%), comprising one out of three with MSS/MSI-low and BRAF-mutated disease, one out of 15 with MSS/MSI-low and BRAF wild-type tumors, and all three with MSI-high profiles. The regimen of SHR7390 at 0.5 mg combined with camrelizumab exhibited an acceptable safety profile. Early signs of therapeutic efficacy were observed independent of microsatellite instability or BRAF mutation status.
