Several abstracts and data presentations on emerging clinical research in metastatic colorectal cancer (mCRC) prompted expert interest and discussion at the American Society of Clinical Oncology (ASCO) 2026, held 29 May to 2 June 2026.
Two of these abstracts were Cardiff Oncology’s Phase II randomised CRDF-004 trial of onvansertib and Shanghai Kechow Pharma’s sponsored Phase III, randomised, open-label trial of Kolupin. GlobalData Healthcare analysts looked further into how these therapies could impact patient populations.
Go deeper with GlobalData
Access deeper industry intelligence
Experience unmatched clarity with a single platform that combines unique data, AI, and human expertise.
Cardiff Oncology’s onvansertib added to SoC
Cardiff Oncology’s trial Phase II randomised CRDF-004 trial (NCT06106308) enrolled patients with rat sarcoma (RAS)-mutated unresectable mCRC receiving first-line standard of care (SoC) chemotherapy FOLFIRI (leucovorin + fluorouracil + irinotecan) or FOLFOX (leucovorin + fluorouracil + oxaliplatin) plus bevacizumab.
To this backbone, Cardiff Oncology’s onvansertib, an oral small molecule polo-like-kinase 1 (PLK1) inhibitor, was added at two dose levels, 20mg and 30mg, and compared against SoC alone. The primary endpoint was objective response rate (ORR), with key secondary endpoints including progression-free survival (PFS), duration of response (DoR), and safety.
With data still maturing, the presented results suggest the trial is on course to meet its primary endpoints, as onvansertib in combination with FOLFIRI and bevacizumab showed promising antitumor activity and acceptable safety. In contrast, the combination of onvansertib with FOLFOX did not demonstrate benefit in this setting.
A total of 110 patients were enrolled and randomised across six arms: bevacizumab plus FOLFIRI or bevacizumab plus FOLFOX, each with or without onvansertib 20mg or 30mg, with baseline characteristics largely balanced across arms. The onvansertib 30mg plus FOLFIRI plus bevacizumab arm achieved the highest confirmed ORR of 72.2%, compared with 42.1% in the FOLFIRI plus bevacizumab control arm, 44.4% for FOLFOX plus bevacizumab.
Moreover, when comparing onvansertib (20mg and 30mg) plus FOLFIRI–bevacizumab with SoC, median PFS in the experimental arms was not reached versus 10.97 months for FOLFIRI plus bevacizumab per investigator assessment, yielding a PFS hazard ratio (HR) of 0.53.
The safety profile reported was manageable, with neutropenia as the most common Grade 3 or higher adverse event (AE). While the results are encouraging, per-arm sample sizes remain small with confirmatory evidence needed, and the company has already announced a Phase III evaluation of onvansertib 30mg plus FOLFIRI and bevacizumab.
Treatment of RAS-mutant mCRC represents one of the most significant unmet needs within the indication. According to GlobalData’s Colorectal Cancer: Eight-Market Drug Forecast and Market Analysis 2021–32 report, KRAS and NRAS mutations occur in approximately 45% of mCRC patients and correlate with resistance to anti-epidermal growth factor receptor (EGFR) therapies. The KRAS G12C mutation, which has seen targeted therapies emerge in later lines, is relatively uncommon, occurring in 3-4% of mCRC cases. As a result, bevacizumab plus chemotherapy remains the first and second-line SoC, a paradigm that has gone unchanged for two decades, yet PFS with this regimen remains poor, at nine to 11 months, underscoring the urgent need for more effective therapeutic strategies.
Against this backdrop, onvansertib has emerged as a distinctive development-stage asset. It is currently the only agent in late-stage development to offer a mutation-agnostic approach, positioning it as potentially applicable across the full spectrum of RAS-mutant disease and irrespective of specific mutation subtype. Beyond CRC, onvansertib is also under clinical investigation across a broad range of malignancies, including pancreatic cancer, chronic myelomonocytic leukaemia, breast cancer, small-cell lung cancer, and skin cancer. Commercial expectations reflect this breadth of opportunity. According to GlobalData’s analyst consensus forecast, onvansertib is projected to reach $1bn in sales by 2032.
Shanghai Kechow Pharma’s Kolupin combo meets primary endpoint
Results were also presented from Shanghai Kechow Pharma’s sponsored Phase III, randomised, open-label trial (NCT06008119), in patients with B-type rapidly accelerated fibrosarcoma (BRAF) V600E–mutant metastatic colorectal cancer (mCRC) who had received at least one prior line of systemic therapy.
Patients in the experimental arm received Kolupin (tunlametinib), Shanghai Kechow Pharma’s novel oral mitogen-activated extracellular signal-regulated kinase (MEK1/2) inhibitor, plus Zelboraf (vemurafenib), Roche’s BRAF inhibitor, versus the investigator’s choice therapy. The primary endpoint was PFS, with key secondary endpoints of overall survival (OS), ORR, disease control rate (DCR), and safety.
The tunlametinib plus vemurafenib combination delivered a statistically significant improvement in PFS versus control. Median PFS was 4.2 months in the experimental arm versus 1.5 months in the control arm, with an HR of 0.342.
Confirmed ORR was 26.7% versus 3.7%, and DCR was 85.7% versus 40.4%. OS data remains immature. However, baseline characteristics were not fully balanced between arms: ≥3 metastatic sites were present in 61.9% of patients in the experimental arm versus 46.2% in the control arm, which may have influenced outcomes.
Notably, the tunlametinib plus vemurafenib trial was initiated before the BREAKWATER (NCT04607421) trial results were available. Patients were BRAF inhibitor-naïve at enrolment, with doublet or triplet chemotherapy used as the first-line treatment. An important question is therefore how these results fit within the evolving treatment landscape, given that BREAKWATER has since established a new frontline standard: Pfizer’s Braftovi (encorafenib) plus cetuximab and chemotherapy received US Food and Drug Administration (FDA) approval, demonstrating a doubling of OS in BRAF V600E–mutant mCRC with a median PFS of 12.8 months and median OS of 30.3 months, representing one of the most significant breakthroughs in CRC in recent years.
In the previously-treated setting, the BEACON CRC trial set the benchmark, with Braftovi plus cetuximab delivering a median PFS of 4.2 months and median OS of 8.4 months. This further raises the question of whether replacing vemurafenib with encorafenib in this combination could yield meaningfully improved outcomes. The VIC regimen (vemurafenib, irinotecan, and cetuximab/panitumumab) was the first BRAF V600E–targeted combination to receive the US National Comprehensive Cancer Network (NCCN) recommendation in CRC, but was subsequently removed from the guidelines in favour of newer BRAF-targeted regimens offering more mature efficacy data and an improved tolerability profile. BREAKWATER has shrunk the pool of BRAF inhibitor-naïve patients in later lines, the very population studied here. The post-encorafenib retreatment space, while an active area of investigation, appears to be consolidating around encorafenib-cetuximab rechallenge strategies rather than alternative BRAF inhibitor combinations, further limiting the likely niche for tunlametinib plus vemurafenib.
The extent to which these findings translate to a global setting remains uncertain. Notably, over 50% of enrolled patients had left-sided tumours despite BRAF V600E–mutant colorectal cancer being well established as predominantly right-sided. The presenter attributed this to geographic differences within the Chinese population. As the trial was conducted exclusively in China, differences in tumour biology may limit applicability to Western patients, and regulatory agencies such as the FDA and European Medicines Agency (EMA) may require additional bridging studies before granting approval.
