ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03829410 (A Phase 1b/2 Study of Onvansertib), which is not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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
Who cites it
35 citing papers in PubMed.
- Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Correction: Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Systematic review and meta-analysis of studies assessing circulating tumor DNA kinetics in metastatic colorectal cancer.ESMO gastrointestinal oncology · 2026Review
- Targeting PLK1 Reduces MMP10 to Enhance Radiosensitivity in HPV- Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Targeting PLK1 potentiates the antitumor efficacy of EGFR-TKIs through inhibiting the JAK1/STAT3 pathway.Cell death & disease · 2026Article
- KRAS-Driven Hypertranscription and Metastatic Dissemination in Colorectal Cancer Could be Overcome by Targeting the NMHC IIA/ PLK1 Signaling Axis with a Novel Acridine Derivative.International journal of biological sciences · 2026Article
- PLK1 stabilizes β-catenin to drive colorectal carcinogenesis through NFKB2-mediated transcriptional activation of USP2a and site-specific phosphorylation.Theranostics · 2026Article
- Investigating radiotherapy's impact on intestinal perforation risk in gastrointestinal tumor patients treated with bevacizumab.World journal of gastrointestinal oncology · 2025Article
- A core stemness-associated module reveals PLK1, NUF2, KIF23, CDCA8, TOP2A, CENPF, AURKA, and ASPM as key genes in rectal cancer.European journal of medical research · 2025Article
- PLK1 inhibition enhances gemcitabine-induced apoptosis through PLK1-dependent ERK1/2-Bim and AKT1/Noxa signals in pancreatic cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Article
- Polo-like kinase 1 inactivation enhances PI3K inhibition-mediated apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma.Cancer letters · 2025Article
- Review
- Polo-Like Kinase 1 Expression in Colorectal Cancer: Association With RAS Mutations.Cancer science · 2025Article
- Differential Response and Resistance to KRAS-Targeted Therapy.Molecular carcinogenesis · 2025Review
- PLK1 inhibitors for the treatment of colorectal cancer.Annals of medicine and surgery (2012) · 2025Review
- Overexpression of oncogenic polo-like kinase 1 disrupts the invasiveness, cell cycle, and apoptosis in synovial sarcoma.Journal of translational medicine · 2025Article
- Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma.Cell reports. Medicine · 2025Article
- Review
- Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.International journal of molecular sciences · 2025Article
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
purposeOnvansertib is a highly specific inhibitor of polo-like kinase 1 (PLK1), with demonstrated safety in solid tumors. We evaluated, preclinically and clinically, the potential of onvansertib in combination with chemotherapy as a therapeutic option for KRAS-mutant colorectal cancer. PATIENTS AND
methodsPreclinical activity of onvansertib was assessed (i) in vitro in KRAS wild-type and -mutant isogenic colorectal cancer cells and (ii) in vivo, in combination with irinotecan, in a KRAS-mutant xenograft model. Clinically, a phase Ib trial was conducted to investigate onvansertib at doses 12, 15, and 18 mg/m2 (days 1-5 and 14-19 of a 28-day cycle) in combination with FOLFIRI/bevacizumab (days 1 and 15) in patients with KRAS-mutant metastatic colorectal cancer who had prior oxaliplatin exposure. Safety, efficacy, and changes in circulating tumor DNA (ctDNA) were assessed.
resultsIn preclinical models, onvansertib displayed superior activity in KRAS-mutant than wild-type isogenic colorectal cancer cells and demonstrated potent antitumor activity in combination with irinotecan in vivo. Eighteen patients enrolled in the phase Ib study. Onvansertib recommended phase II dose was established at 15 mg/m2. Grade 3 and 4 adverse events (AE) represented 15% of all treatment-related AEs, with neutropenia being the most common. Partial responses were observed in 44% of patients, with a median duration of response of 9.5 months. Early ctDNA dynamics were predictive of treatment efficacy.
conclusionsOnvansertib combined with FOLIFRI/bevacizumab exhibited manageable safety and promising efficacy in second-line treatment of patients with KRAS-mutant metastatic colorectal cancer. Further exploration of this combination therapy is ongoing. See related commentary by Stebbing and Bullock, p. 2005.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.