Study of Onvansertib Plus SOC in Metastatic Colorectal Cancer Enters Phase 2


Following reports of durable response in a phase 1 study, the combination of onvansertib FOLFIRI, and bevacizumab will be evaluating in a phase 2 study of patients with metastatic colorectal cancer.

Second-line treatment with onvansertib will be assessed in combination with irinotecan, fluorouracil (5-FU), and folinic acid (leucovorin; FOLFIRI), and bevacizumab (Avastin) in patients with RAS-mutated metastatic colorectal cancer (mCRC).1

Plans for the phase 2 ONSEMBLE study (NCT03829410) were announced in a press release by Cardiff Oncology. The study will follow reports that onvansertib plus FOLFIRI/bevacizumab achieved a median duration of response of 11.7 months in a phase 1 trial. Preclinical data around onvansertib and irinotecan showed that the combination can overcome resistance to irinotecan.

About the ONSEMBLE Study

Trial Name: A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Patients With a Kras Mutation Indentifier: NCT03829410

Completion Date: December 2023

Sponsor: Cardiff Oncology

“These results show patients with different KRAS mutations experiencing durable responses to treatment with onvansertib plus standard-of-care, with an objective response rate and median progression-free survival that are well above historical benchmarks. In line with the FDA's Project Optimus initiative, the ONSEMBLE trial will also seek to confirm the optimal dose of onvansertib in mCRC. We believe achieving these objectives could position onvansertib for a possible accelerated approval opportunity, though this would ultimately depend on the strength of the ONSEMBLE trial results,” said Mark Erlander, PhD, chief executive officer of Cardiff Oncology, about the phase 1/2 research, in a press release.

ONSEMBLE is a sequential assignment study that will include roughly 100 patients with mCRC in the second-line setting. The study’s primary end point of the phase 2 study is the objective response rate, and the key secondary end points include disease control rate, the number of patients with adverse events (AEs), progression-free survival, duration of response, overall survival, the number of patients with reduction in KRAS allelic burden on liquid biopsies.2

To be eligible for the study, patients aged 18 years or older must histologically confirmed metastatic and unresectable CRC, documentation of a KRAS mutation, available tumor tissue, and an ECOG performance status of 0 or 1. Patients cannot be receiving any other standard-of-care or experimental cancer therapy. All patients must have failed treatment or become intolerant of fluoropyrimidine and oxaliplatin with or without bevacizumab. The study is actively recruiting patients at sites across the United States.

“We designed our next clinical program in mCRC, a randomized Phase 2 trial we have named ONSEMBLE, to accelerate and de-risk our lead indication," said Erlander. "Chief among ONSEMBLE's objectives is to generate a randomized dataset to demonstrate the contribution of onvansertib over standard-of-care alone, validating the phase 1b/2 trial results.


1. Cardiff Oncology announces plans for a randomized trial in metastatic colorectal cancer (mCRC), durability of responses in ongoing phase 1b/2 trial in mCRC and additional business updates. News release. Cardiff Oncology. September 12, 2022. Accessed September 15, 2022.

2. Onvansertib in combination with FOLFIRI and bevacizumab for second line treatment of metastatic colorectal cancer patients with a KRAS mutation. Updated August 26, 2022. Accessed September 15, 2022.

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