“The posters we will be presenting at this year’s AACR meeting represent a broad view of the potential of onvansertib in several different cancer indications, including RAS-mutant mCRC, RAS-wild type mCRC, small cell lung cancer and ovarian cancer,” said
Details on the posters and corresponding abstracts are shown below.
Poster Title: A phase 1b/2 clinical study of onvansertib in combination with FOLFIRI/bevacizumab revealed a new role of PLK1 in regulating the hypoxia pathway in KRAS-mutant colorectal cancer
Session Title: Microenvironment, Immunity, and DNA Repair in Therapeutic Response
Session Date and Time:
Location: Poster Section 27, Poster Board #14, Abstract Number #2031
This abstract presents updated clinical data and biomarker analysis from the Phase 1b/2 study evaluating onvansertib in combination with FOLFIRI/bevacizumab for second-line treatment of KRAS-mutant metastatic colorectal cancer (mCRC) patients. Analysis of patient baseline characteristics revealed superior clinical benefit in patients not exposed to bevacizumab in first-line treatment (Bev-naïve) compared to Bev-exposed patients. Bev-naive patients exhibited higher objective response rates (73.3% versus 15.7%) and longer median progression-free survival (14.9 versus 7.8 months) compared to Bev-exposed patients. Preclinical studies, using KRAS-mutant colorectal cancer mouse models revealed robust antitumor activity of onvansertib in combination with bevacizumab and a novel role of onvansertib in regulating tumor vascularization. Further preclinical investigations showed that PLK1 regulates the hypoxia pathway in KRAS-mutant CRC cells through the modulation of the hypoxia-inducible factor 1 alpha, HIF1α, emphasizing the potential crosstalk between PLK1 and angiogenesis. These findings reinforce the rationale for exploring onvansertib in combination with FOLFIRI/bevacizumab for Bev-naïve mCRC patients with KRAS mutation.
Poster Title: The PLK1 inhibitor, onvansertib, is active as monotherapy and in combination with cetuximab in RAS wild-type colorectal cancer patient-derived xenografts
Session Title: Drug Resistance 2: Ras GTPase
Session Date and Time:
Location: Poster Section 24, Poster Board #12, Abstract Number #1934
This abstract focuses on the preclinical assessment of onvansertib’s antitumor activity in RAS wild-type colorectal cancer, as both a monotherapy and in combination with cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Employing patient-derived xenograft (PDX) models, the study highlights the robust antitumor efficacy of onvansertib monotherapy, in cetuximab-sensitive and -resistant RAS wild-type colorectal cancer models. Furthermore, the combination of onvansertib and cetuximab was highly effective, resulting in tumor regression in 90% of the PDXs. These compelling data strongly support the clinical development of onvansertib as a potential treatment for RAS wild-type colorectal cancer.
Poster Title: A phase 2, randomized, open-label study of onvansertib in combination with standard-of-care (SoC) versus SoC alone for first-line treatment of RAS-mutant metastatic colorectal cancer(mCRC)
Session Title: Phase II and Phase III Clinical Trials in Progress
Session Date and Time:
Location: Poster Section 50, Poster Board #5, Abstract Number #CT275
This abstract describes a clinical trial in progress.
Poster Title: The PLK1 inhibitor, onvansertib, synergizes with paclitaxel in small cell lung cancer
Session Title: Kinase and Phosphatase Inhibitors 1
Session Date and Time:
Location: Poster Section 25, Poster Board #16, Abstract Number #606
This abstract outlines preclinical studies showing the promising potential of combining onvansertib with paclitaxel for small cell lung cancer (SCLC). The research reveals significant synergy of the combination in SCLC cell lines and demonstrates its robust antitumor activity in patient-derived xenograft models, including models resistant to the standard therapy cisplatin. Further insights into the combination's mechanism of action will be presented. These findings support that combining onvansertib with paclitaxel could emerge as a highly promising treatment strategy for SCLC.
Poster Title: In vivo anti-tumor activity of onvansertib, a PLK1 inhibitor, combined with gemcitabine or carboplatin in platinum-resistant ovarian carcinoma patient-derived xenograft models
Session Title: Application of Precision Medicine for Cancer Care
Session Date and Time:
Location: Poster Section 39, Poster Board #13, Abstract Number #945
This abstract explores preclinically the potential of combining onvansertib with the chemotherapeutic agents carboplatin or gemcitabine for platinum-resistant high-grade ovarian carcinoma. Using patient-derived xenografts, we demonstrated robust efficacy for both combinations, coupled with favorable tolerability. These data underscore the potential of onvansertib to improve the efficacy of the standard-of-care carboplatin and gemcitabine for patients with platinum-resistant high-grade ovarian carcinoma.
The abstracts are available on the AACR Online Program and will be published in the online Proceedings of the AACR. Following presentation, the posters will be posted to the "Scientific Presentations" section of the
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