Onvansertib Yields Positive Activity in SCLC and Pancreatic Cancer

Developers also highlighted findings from a metastatic PDAC biomarker discovery trial, in which 2 patients have enrolled and received 10-day onvansertib monotherapy to date. Investigators reported an 86% decrease in Ki67 in one patient, and a 28% reduction in CA 19-9 in another.

Investigators reported positive clinical activity with onvansertib as a treatment for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and relapsed extensive-stage small cell lung cancer (ES-SCLC), according to a press release from Cardiff Oncology, Inc.

According to findings from the phase 2 CRDF-001 trial (NCT04752696), combining onvansertib with nanoliposomal irinotecan, leucovorin, and 5-fluorouracil produced an objective response rate (ORR) of 19% (n = 4/21) in the second-line setting among patients with metastatic PDAC as of the data cutoff date of September 13, 2023. Additionally, the combination yielded a median progression-free survival (PFS) of 5.0 months. This compared favorably with historical control trials assessing standard of care, which reported an ORR of 7.7% and median PFS of 3.1 months.

In another phase 2 trial (NCT05450965) evaluating onvansertib on its own among those with previously treated relapsed ES-SCLC, a review of safety data concerning the first 6 treated patients by an institutional review board permitted investigators to continue enrollment.

Investigators also plan to initiate a new phase 2 trial evaluating onvansertib in frontline metastatic PDAC. In one cohort, patients will receive onvansertib plus gemcitabine (Gemzar) and paclitaxel (Abraxane); in another, patients will receive onvansertib for 10 days followed by onvansertib plus standard of care to determine biomarkers that may predict response to the experimental agent.

“We are excited that the data released from these trials, in 2 challenging cancers with low survival rates, expands the opportunity for onvansertib beyond our lead program in RAS-mutated [metastatic colorectal cancer],” Mark Erlander, PhD, chief executive officer at Cardiff Oncology, said in the press release. “In pancreatic cancer, the strength of the data provides a clear rationale for a first-line trial using onvansertib in combination with standard of care, which we believe provides the greatest opportunity for a positive impact on patients. In [SCLC], we are encouraged to observe single-agent activity with onvansertib monotherapy in this difficult-to-treat extensive stage refractory setting.”

In the safety lead-in portion of the phase 2 CRDF-001 trial, patients received onvansertib at 12 mg/m² on day 1 to day 10 for 2 cycles that lasted 2 weeks each. Additionally, patients received 70 mg/m² of nanoliposomal irinotecan plus 400 mg/m² of leucovorin and 2400 mg/m² fluorouracil.

The trial’s primary end point was ORR. Secondary end points included duration of response, overall survival, disease control rate, and treatment-emergent adverse effects (AEs).

In the single-arm phase 2 SCLC trial, patients received onvansertib orally at 15 mg/m² on days 1 to 14 during a 21-day cycle, with treatment continuing until unacceptable toxicity or disease progression.

The trial’s primary end point was ORR per RECIST v1.1 criteria, with secondary end points including PFS, OS, and AEs.

Developers also highlighted findings from a metastatic PDAC biomarker discovery trial, in which 2 patients have enrolled and received 10-day onvansertib monotherapy to date. Investigators reported an 86% decrease in Ki67 in one patient, and a 28% reduction in CA 19-9 in another.

“We are encouraged by the ability of onvansertib to provide an approximately 30% reduction in this biomarker with only 10 days of monotherapy in a refractory setting. We will continue to explore onvansertib in the first-line [metastatic] PDAC investigator-initiated trial at the Oregon Health & Science University [OHSU] Knight Cancer Institute,” Fairooz Kabbinavar, MD, chief medical officer at Cardiff Oncology, concluded.

Reference

Cardiff Oncology announces positive clinical data in pancreatic cancer and small cell lung cancer, including single-agent activity from onvansertib monotherapy. News release. Cardiff Oncology. September 26, 2023. Accessed October 9, 2023. https://bit.ly/3PGkigU