Clinical Update: Phase 2 ONSEMBLE Trial for RAS-mutated mCRC Patients

Cardiff Oncology, Inc., a biotech firm at the clinical stage, is focused on inhibiting PLK1 to devise new treatments for various cancers. Recently, they shared a clinical update from their second-line ONSEMBLE trial for RAS-mutated metastatic colorectal cancer (mCRC). Although this Phase 2 trial was halted to transition efforts to a first-line mCRC program, it initially enlisted 23 participants spread across three groups before closing to new candidates. These patients continued their treatment as per the trial protocol. The clinical data reinforced the previous efficacy results of onvansertib from the earlier Phase 1b/2 trial for KRAS-mutated mCRC patients who had not previously received bevacizumab (bev).

Fairooz Kabbinavar, MD, FACP, Chief Medical Officer at Cardiff Oncology, stated that the randomized data from ONSEMBLE underscores the potential of onvansertib in the first-line setting for RAS-mutated mCRC. The only objective responses were observed in bev-naive patients given onvansertib alongside standard treatments, an indication that this combination was well-tolerated. He noted that transitioning the main program to the first-line setting ensures all patients in the CRDF-004 trial are bev-naive. He emphasized the lack of responses in control-arm patients and those who had received bev previously, suggesting that onvansertib enhances the efficacy of standard therapies when used from the outset. Cardiff anticipates sharing the topline results of the CRDF-004 trial in mid-2024.

In August 2023, Cardiff halted enrollment in the second-line ONSEMBLE trial to concentrate on their first-line mCRC program. This strategic decision took into account the similarity in hypotheses tested by both trials, the need for efficient capital use, and the FDA's recommendation to focus on first-line settings due to the absence of new therapies for this significant cancer type in the past two decades.

Before halting enrollment, the ONSEMBLE trial had 23 randomized patients across three trial arms: a control arm with standard therapy (FOLFIRI+bev), one experimental arm with an added dose of 20mg onvansertib, and another with 30mg onvansertib, both combined with FOLFIRI+bev. These patients had documented KRAS or NRAS mutations and had prior chemotherapy treatments with or without bev in the first-line metastatic setting. The combination treatments involving onvansertib and SoC FOLFIRI/bev showed tolerability with no unexpected severe toxicities. Two patients experienced Grade 4 neutropenia but recovered promptly after pausing treatment without the need for subsequent dose reductions.

The enrolled patients had a median age of 53 years and were 54% male. Approximately 68% had previously received bev in their initial treatments. At the data cutoff, 12 of the 21 evaluable patients remained in the trial.