Key takeaways
- The 30 mg onvansertib arm demonstrated a 49% confirmed ORR versus 30% with standard-of-care alone, with early PFS trends and dose-dependent efficacy supporting further evaluation.
- The trial met safety expectations, with onvansertib showing a favorable tolerability profile and low rates of grade ≥3 adverse events, primarily neutropenia.
- CRDF-004’s six-arm design and exploratory endpoints provide a robust framework for assessing combination strategies and are informing plans for a registrational CRDF-005 trial.
Cardiff Oncology has shared new, positive data from the ongoing Phase II CRDF-004 (NCT06106308) clinical trial of onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC). The data from this readout represents intent-to-treat patients as of a July 8, 2025 data cut-off.1
Confirmed ORR reaches 49% with 30 mg onvansertib
According to the results:
- The confirmed objective response rate (ORR) was 49% in the 30 mg onvansertib arm compared to 30% in the control arm.
- Early progression-free survival (PFS) data showed a favorable trend for the 30 mg onvansertib arm over the control arm.
- Both the 20 mg and 30 mg dose groups showed early separation of PFS curves from the control at a 6-month median follow-up.
- A dose-dependent response was observed across all efficacy endpoints, including ORR, early tumor shrinkage, and depth of response.
Company highlights speed and depth of tumor regression
In a press release, Roger Sidhu, MD, chief medical officer of Cardiff Oncology, said: “We are highly encouraged by the 19% improvement in confirmed ORR as well as the shorter time to response and deeper tumor regression observed in our trial with onvansertib combined with SoC compared to SoC alone. Furthermore, early PFS data shows a trend favoring the 30mg dose of onvansertib vs. control. The totality of the data we are releasing today strengthens the initial findings from our December 2024 data release in a significantly larger patient population, compares favorably to previous practice-changing Phase III trials, and demonstrates that onvansertib could be a novel therapy for the treatment of first-line RAS-mutated mCRC.”
Safety profile supports continued development
In terms of safety, data from CRDF-004 showed:
- Onvansertib combined with chemotherapy and bevacizumab was generally well-tolerated.
- No major or unexpected toxicities were reported.
- Grade 3 or higher adverse events were infrequent, with neutropenia being the most common treatment-emergent event linked to onvansertib.
Mark Erlander, chief executive officer of Cardiff Oncology, added: “We are highly encouraged by the strength of our data which achieves the key objectives we set for the trial, and positions us to engage in discussions with the FDA as we advance toward our registrational CRDF-005 trial. Looking ahead, we are optimistic about onvansertib’s potential to redefine the first-line treatment for RAS-mutated mCRC and will provide an update on our first-line mCRC program by Q1 2026.”
December 2024 results laid early foundation
Cardiff Oncology announced initial data from CRDF-004 in December 2024. Results from this earlier readout showed:2
- In RAS-mutated mCRC, the 30 mg onvansertib dose combined with SoC produced a 64% objective response rate versus 33% in the control arm.
- The 30 mg onvansertib dose also outperformed the 20 mg dose, with response rates of 64% and 50%, respectively.
- Deeper tumor regression was observed in the 30 mg arm compared to the 20 mg arm.
- Onvansertib was well tolerated at both dosing levels.
Study design includes six-arm randomization
CRDF-004 is a randomized, open-label Phase II study evaluating onvansertib in combination with SoC for the first-line treatment of mCRC in patients with a KRAS or NRAS mutation.3
- Participants received SoC treatment with either FOLFIRI plus bevacizumab or FOLFOX plus bevacizumab.
- Patients were randomized into six arms, including 20 mg onvansertib plus SoC, 30 mg onvansertib plus SoC, or SoC alone.
- The primary endpoint was ORR, with secondary endpoints including PFS, duration of response, and safety.
- Prespecified exploratory measures included early tumor shrinkage, defined as at least 20% reduction in tumor size at two months, and depth of response, defined as the maximum tumor size reduction achieved during treatment.
References
1. Cardiff Oncology Announces Positive Data from Ongoing Randomized Phase 2 First-line RAS-mutated mCRC Clinical Trial (CRDF-004). News release. Cardiff Oncology. July 29, 2025. Accessed July 31, 2025. https://investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-data-ongoing-randomized
2. Cardiff Oncology Announces Positive Initial Data from First-line RAS-mutated mCRC Clinical Trial. News release. Cardiff Oncology. December 10, 2024. Accessed July 31, 2025. https://investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-initial-data-first-line-ras
3. Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer in Adult Participants With a KRAS or NRAS Mutation. ClinicalTrials.gov. Updated April 29, 2025. Accessed July 31, 2025. https://clinicaltrials.gov/study/NCT06106308
