onvansertib (PCM-075) / Nerviano Medical Sciences, Cardiff Oncology - LARVOL DELTA

PANCONVA: Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: University of Kansas Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Solid Tumor

Inhibition of PLK1 helps to restrict c-Met-induced growth and therapeutic resistance of renal cancer cells. (PubMed, Mol Cancer Ther) - "Following combination treatment, there was increased drug-induced cytotoxicity, and markedly reduced tumor growth in vivo. Together, our pre-clinical study identifies that cabo + onvansertib is an effective combination treatment to overcome c-Met-induced therapeutic resistance in RCC with translational potential."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • MET • PLK1

Cardiff Oncology and Nerviano Medical Sciences Amend their 2017 Exclusive License Agreement (The Manila Times) - "Cardiff and NMS have agreed to a full and mutual release of all claims asserted in the litigation pending in the U.S. District Court for the Southern District of California. Cardiff and NMS plan to jointly request dismissal of all claims with prejudice....The Parties clarified and expanded on the royalty structure in the License Agreement. The agreement also includes development objectives related to Cardiff’s upcoming Phase 3 program, as well as rights for NMS to appoint a Board observer and join Cardiff’s Scientific Advisory Board."

Licensing / partnership • Colorectal Cancer

Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. (PubMed, J Clin Oncol) - P2 | "Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with KRAS-mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308)."

Combination therapy • Journal • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Onvansertib plus standard-of-care chemotherapy plus bevacizumab in first-line RAS-mutated metastatic colorectal cancer (mCRC): Interim results from the phase 2 randomized CRDF-004 trial. (ASCO 2026) - P2 | "Onvansertib plus FOLFIRI and bevacizumab demonstrated improved antitumor activity and manageable safety in first-line RAS-mutated mCRC. These results support further clinical and support planned confirmatory Phase 3 evaluation."

Clinical • Metastases • P2 data • Colorectal Cancer • Neutropenia • Oncology • Solid Tumor • KRAS

A phase 1b study of Plk1 inhibitor onvansertib in combination with paclitaxel in metastatic triple-negative breast cancer (mTNBC) patients. (ASCO 2025) - P1/2 | "The combination of onvansertib and P demonstrated a safe toxicity profile and promising clinical activity in pretreated mTNBC pts and warrant further exploration of the combination at the RP2D. Best response per RECIST 1.1 among different DL."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Anemia • Breast Cancer • Fatigue • Oncology • Solid Tumor • Triple Negative Breast Cancer • PLK1

Onvansertib-mediated PLK1 inhibition impairs spermatogenesis in the murine testis. (PubMed, Asian J Androl) - "This disruption is likely linked to impaired meiotic centrosome maturation and aberrant spindle organization in germ cells. Collectively, these findings demonstrate that ONV preferentially induces apoptosis in germ cells via PLK1 suppression, thereby compromising spermatogenic capacity."

Journal • Preclinical • Oncology • EIF4E • EIF4EBP1

Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. (PubMed, Ann Hematol) - "In the phase 1b/2 trial, patients with SF mutations (SRSF2, SF3B1) had a higher CR/CRi rate (50%) compared to those without SF mutations (9%). PLK1 inhibition with ONV in combination with DAC could be a potential therapy in R/R AML patients, particularly those with high OXPHOS gene expression and SF mutations."

Combination therapy • Journal • P1/2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • SF3B1 • SRSF2

Targeted Pathway Inhibition in Patients With Pancreatic Cancer (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: OHSU Knight Cancer Institute | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Completed Successful End-of-Phase 2 ("EoP2”) Meeting with FDA and Advanced Phase 3 Readiness Activities (The Manila Times) - "Following completion of a successful EoP2 meeting, Cardiff aligned with the FDA on key design elements for its planned registrational Phase 3 trial of onvansertib in first-line RAS-mutated mCRC. The planned randomized, controlled Phase 3 trial is expected to evaluate 30 mg onvansertib in combination with FOLFIRI/bev compared to SoC FOLFIRI/bev as first-line therapy in patients with RAS-mutated mCRC. Cardiff is preparing to initiate the trial in the first quarter of 2027, subject to securing additional financing."

FDA event • New P3 trial • Colorectal Cancer

CELL CYCLE–FOCUSED CHEMICAL SCREEN REVEALS MITOTIC KINASE INHIBITORS THAT ENHANCE THE EFFICACY OF A CD30-TARGETED ANTIBODY–DRUG CONJUGATE (EHA 2026) - "Background Brentuximab vedotin (BV), an antibody–drug conjugate (ADC) composed of an anti-CD30 monoclonal antibody conjugated to the microtubule-disrupting drug monomethyl auristatin E (MMAE), is widely used as a key therapeutic agent for the treatment of peripheral T-cell lymphoma (PTCL)...Results The screen identified three compounds—volasertib, GSK461364, and onvansertib—that exhibited strong synergy with BV in both cell lines...Summary/Conclusion Our findings highlight the therapeutic potential of combining BV with PLK1 inhibitors—particularly volasertib—as a rational strategy to enhance cytotoxicity in CD30-positive PTCL. This study provides a mechanistic and preclinical foundation for future clinical evaluation of this combination therapy."

ADC • Clinical • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • CASP3 • CCNB1 • TNFRSF8

Cardiff Oncology Announces Presentation of Positive Results from its Randomized, Controlled Phase 2 Trial of Onvansertib in First-Line RAS-Mutated mCRC at the 2026 ASCO Annual Meeting (GlobeNewswire) - "Registrational trial planned in first-line RAS-mutated mCRC following successful End-of-Phase 2 meeting with FDA...The randomized, controlled Phase 3 trial will evaluate the safety and efficacy of onvansertib 30 mg + FOLFIRI/bev as first-line therapy versus standard-of-care FOLFIRI/bev in patients with RAS-mutated mCRC...Primary endpoint of confirmed objective response rate of 72.2% (13/18), compared with 42.1% (8/19) for FOLFIRI/bev alone, a 30% improvement over standard-of-care (SoC). The responses were deeper and more durable in the onvansertib arm; Secondary endpoint of progression free survival (PFS) hazard ratio (HR) of 0.55 (95% CI: 0.15–2.09) and 0.57 (95% CI: 0.20–1.65) vs. FOLFIRI/bev by Blinded Independent Central Review (BICR) and investigator assessment (IA), respectively; Median PFS not reached in 30 mg onvansertib + FOLFIRI/bev arm, but has been reached in both SoC arms."

New P3 trial • P2 data • Colorectal Cancer

Cardiff Oncology Announces Webcast to Discuss Updated Phase 2 CRDF-004 Data for Onvansertib in First-Line RAS-Mutated mCRC (GlobeNewswire) - "Investor webcast scheduled for June 3, 2026 at 8:30 am ET to review the data....The updated CRDF-004 data will first be presented during a rapid oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting on June 2, 2026 at 8:00 am CT/9:00 am ET and will build on the CRDF-004 data previously presented in January 2026."

P2 data • Colorectal Cancer

Cardiff Oncology Inc. (NASDAQ:CRDF) on Tuesday said that it filed a lawsuit against Nerviano Medical Sciences (NMS), disputing NMS's claim that Cardiff materially breached their licensing agreement for onvansertib. (Benzinga) - "The complaint, filed in the U.S. District Court for the Southern District of California, seeks an injunction requiring NMS to continue honoring the agreement, along with a declaratory judgment that Cardiff did not breach the contract...As previously disclosed in February, NMS alleged Cardiff breached the agreement by failing to name an NMS employee as a joint inventor on Cardiff's U.S. patents 12,144,813 and 12,263,173, and by declining to file a joint invention continuation patent application...The company said discussions with NMS had taken place, but judicial intervention is now necessary."

Corporate lawsuit • Patent • Chronic Myelomonocytic Leukemia • Colorectal Cancer • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Triple Negative Breast Cancer

All Screens Lead to Polo-like kinase 1: A Central Node in Cancer Therapeutics and Resistance. (PubMed, Pharmacol Res) - "Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo- and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment."

Journal • Review • Oncology • PLK1

Upcoming Event: Reporting Updated Onvansertib Data in Rapid Oral Presentation at American Society of Clinical Oncology (ASCO) Annual Meeting 2026 (GlobeNewswire) - "The Company will report detailed updated data from its randomized Phase 2 CRDF-004 trial evaluating onvansertib in combination with FOLFIRI/bev or FOLFOX/bev in patients with first-line RAS-mutated mCRC in a rapid oral presentation at the ASCO Annual Meeting, taking place May 29–June 2 in Chicago."

P2 data • Colorectal Cancer

…Phase 3 Registrational Trial in Patients with First-line RAS-mutated mCRC (GlobeNewswire) - "Additional details of the clinical trial will be shared by mid-2026."

New P3 trial • Colorectal Cancer

Dual targeting of PLK1 and NOTCH signaling synergistically suppresses melanoma progression (SID 2026) - "Treatment of melanoma spheroids with PLK1 inhibitors volasertib (V, 5-25nM) or onvansertib (O, 25-100nM) alone or in combination with NOTCH inhibitor MK-0752 (M, 50-200µM) significantly reduced spheroid proliferation with combination treatment as compared to monotherapies. Interestingly, 101 proteins at ≥;1.5| fold change were solely significant in O-M group as compared to individual treatments, many of which were associated with metabolic pathways. Overall, our data suggests that PLK1 and NOTCH combination could be used as a promising approach for melanoma management."

Melanoma • Solid Tumor • PLK1 • PTEN

Cardiff Oncology...announced that the Company will host a key opinion leader (KOL) webinar to discuss data from an investigator-initiated trial on onvansertib's single-agent clinical activity in chronic myelomonocytic leukemia (CMML). (Yahoo Finance) - "The webinar will take place on Thursday, April 30th, 2026, at 11:00 a.m. ET."

P1 data • Chronic Myelomonocytic Leukemia

Comparative Response of Canine and Human Osteosarcoma Tumour Cell Lines to Molecularly Targeted Anticancer Agents at Clinically Relevant Exposures With Analysis of Genomic Biomarkers. (PubMed, Vet Comp Oncol) - "The results identified four drugs (alisertib, crizotinib, onvansertib and sorafenib) with significant responses at the CRE in cOSA and hOSA cell lines and demonstrated that drug responses were indistinguishable across species. Correlations of drug response with genomic biomarkers in the cOSA cell line panel identified Myc and Hedgehog signalling as potential predictors of crizotinib response and Myc, epithelial markers and anti-apoptotic signalling for onvansertib response. The conclusions of these findings are that cOSA and hOSA cell lines show the same range of response to targeted agents and identify potential biomarker pathways for further investigation in OSA tumours for use in future comparative oncology studies including clinical trials in pet dogs."

Journal • Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Onvansertib-mediated PLK1 inhibition reduces cell viability in neuroblastoma cells (AACR 2026) - "Together, these findings demonstrate that Onvansertib effectively compromises neuroblastoma cell survival through a multifaceted mechanism involving mitotic disruption, DNA damage accumulation and apoptotic activation. By targeting a fundamental regulator of the cell cycle, PLK1 inhibition represents a compelling therapeutic strategy for high-risk neuroblastoma. These data support further exploration of Onvansertib in preclinical models and provide a strong rationale for its advancement toward clinical evaluation in this very prevalent malignancy."

Neuroblastoma • Oncology • Solid Tumor • CASP3 • CDC25C • GNRP

Targeting the PLK1-PRMT5 axis enhances radiosensitivity in prostate cancer (AACR 2026) - "Importantly, both PLK1 inhibition (Onvansertib) and PRMT5 inhibition (Onametostat) synergized with ionizing radiation (IR) to suppress tumor growth in vitro and in vivo. These findings highlight a previously unrecognized role of PLK1-mediated PRMT5 phosphorylation in cell cycle control and radiosensitivity, suggesting that targeting the PLK1-PRMT5 axis may serve as a promising therapeutic strategy to enhance radiotherapy efficacy in prostate cancer."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PLK1 • PRMT5

A PLK1-OCT4 regulatory axis controls lineage plasticity and neuroendocrine differentiation in prostate cancer (AACR 2026) - "We observed a similar plasticity pattern in 16D cells treated with enzalutamide, and in a DOX-inducible LNCaP Rb/p53 knockdown model, where DOX induction likewise promoted a shift toward neuroendocrine features...To test this, we performed in vivo xenograft studies using pre-castrated NSG mice bearing N2P1 tumors and treated animals with vehicle, the PLK1 inhibitor Onvansertib, the BET inhibitor AZD5153, or the combination...Collectively, our findings reveal a critical role for the PLK1-OCT4 axis in prostate cancer plasticity and neuroendocrine differentiation. These results support a therapeutic strategy that simultaneously inhibits PLK1 and BET proteins as a promising approach to slow NEPC progression and improve patient outcomes."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Oncology • Prostate Cancer • Solid Tumor • BRD2 • PLK1 • POU5F1

PLK1 inhibitor onvansertib potentiates the antitumor efficacy of trastuzumab deruxtecan (T-DXd) and reverses its resistance in therapy-resistant HER2-low breast cancer models (AACR 2026) - "Onvansertib, a selective polo-like kinase 1 inhibitor, has shown clinical benefit in combination with the TOP1i irinotecan in metastatic colorectal cancer...The HR+ PDXs originated from primary or metastatic tumors and were resistant to fulvestrant and/or CDK4/6 inhibitors...Taken together, our data indicate that onvansertib enhances T-DXd's antitumor activity and overcomes resistance through synergistic induction of DNA damage and apoptosis. The findings support the clinical potential of this combination for advanced HER2-low breast cancer resistant to standard-of-care therapies."

Clinical • Preclinical • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PLK1

Identification of Polo-like kinase-1 (PLK-1) inhibitors from Centella asiatica (Gotu Kola) using UHPLC and in-silico approaches. (PubMed, Nat Prod Res) - "The 90% ethanol-aqueous extract of C. asiatica whole plant, which was prepared at room temperature, contained ten bioactive compounds including rutin, quercetin, kaempferol, chlorogenic acid, fisetin, apigenin, asiatic acid, fumaric acid, betulinic acid and ursolic acid identified by UHPLC method. As our findings, rutin was identified as a promising PLK-1 inhibitor that exhibited significant docking score -13.07 and high stability within the binding pockets of PLK-1 protein as compared to control drug onvansertib. Furthermore, experimental validation is urgently needed for future translational research to develop rutin as potent PLK-1 inhibitor for treating cancer."

Journal • Oncology • PLK1