What Is Onvansertib?
Onvansertib is an investigational drug currently being studied in clinical trials for various cancers. It is administered as an oral capsule. Clinical trials have investigated doses of 20 mg or 30 mg, often given concurrently with other standard cancer treatments. For example, it has been studied in combination with NALIRIFOX in pancreatic cancer trials. Administration schedules vary, including once daily for 5 days within a 14-day cycle, or once daily for 21 consecutive days followed by 7 days without the drug to complete a 28-day cycle. Onvansertib is being developed by sponsors such as Cardiff Oncology.
As of the latest data, there have been 13 clinical trials involving Onvansertib, with a total enrollment of 612 participants. These trials began in 2017 and continue to the present, with some trials currently recruiting new participants.
Uses and Conditions Under Study
Onvansertib is being investigated for its potential use in several types of cancer, often in combination with existing therapies.
- Pancreatic Cancer: This deadly disease is a major focus of Onvansertib research. Trials are studying Onvansertib for Stage II, Stage III, and Stage IV Pancreatic Cancer AJCC v8, as well as Locally Advanced Pancreatic Ductal Adenocarcinoma and Metastatic Pancreatic Ductal Adenocarcinoma. These conditions are being explored in a total of 10 trials. Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030, with a high mortality rate within 5 years of diagnosis.
- Metastatic Colorectal Cancer: Onvansertib is being studied in 4 trials for patients with Metastatic Colorectal Cancer. This research aims to evaluate its effectiveness when combined with other treatments for this advanced form of cancer.
- Breast Cancer: Several breast cancer types are under investigation, including Hormone Receptor/Growth Factor Receptor-Negative Breast Cancer, Inflammatory Breast Cancer, and Invasive Breast Cancer. A phase 1b/2 study is specifically exploring Onvansertib in combination with paclitaxel for patients with triple-negative invasive breast cancer that is unresectable locally advanced or metastatic. These conditions are being studied across 3 trials.
- KRAS Gene Mutation: Onvansertib is also being investigated in 2 trials for cancers characterized by a KRAS Gene Mutation. This genetic alteration is common in several cancers, including pancreatic and colorectal cancers, and is a target for new therapeutic approaches.
Dosing
Onvansertib is administered orally as a capsule. Clinical trials have explored different strengths and administration schedules, often in combination with other standard-of-care treatments.
The studied doses of Onvansertib include 20 mg and 30 mg. These doses are typically given as a flat dose, meaning the same dose for all patients, rather than adjusted by weight.
Administration schedules for Onvansertib have varied across studies:
- One common schedule involves taking Onvansertib once daily for 5 consecutive days within a 14-day treatment cycle.
- Another schedule involves taking Onvansertib once daily for 21 consecutive days, followed by a 7-day break without the drug, to complete a 28-day cycle.
Onvansertib has been studied in combination with various other medications, including NALIRIFOX, paclitaxel, FOLFIRI + Bevacizumab, abiraterone and prednisone, low-dose cytarabine, and decitabine. Some trials involve dose escalation phases to determine the optimal and safest dose when used in these combinations, such as in studies like NCT04327708 and NCT05072739.
Side Effects
Specific types of side effects experienced by patients taking Onvansertib were not detailed in the provided study results. Instead, the data reports the number of participants who experienced any adverse event (AE) or dose-limiting toxicity (DLT).
In a study of Onvansertib in combination with either Decitabine or Low-dose Cytarabine for Acute Myeloid Leukemia (NCT03303339):
- In Phase 1b, 2 participants experienced dose-limiting toxicities (DLTs) when treated with Onvansertib 90 mg/m^2 and Decitabine. No DLTs were reported at lower doses of Onvansertib in combination with either Decitabine or Low-dose Cytarabine.
- In Phase 2, up to 32 participants experienced adverse events (AEs) when treated with Onvansertib 60 mg/m^2 and Decitabine.
For patients with Metastatic Castration-Resistant Prostate Cancer receiving Onvansertib in combination with Abiraterone and Prednisone (NCT03414034):
- D
Currently Recruiting Trials
Onvansertib is currently being investigated in several clinical trials for various cancers. These studies aim to understand its safety, effectiveness, and optimal dosage, offering new treatment possibilities for patients. One ongoing Phase 1/Phase 2 study, NCT06736717, is exploring Onvansertib in combination with NALIRIFOX for the first-line treatment of advanced pancreatic cancer. This trial, sponsored by the University of Kansas Medical Center, is recruiting up to 21 participants. Pancreatic cancer is a particularly challenging disease, and this study seeks to improve outcomes for those diagnosed. For patients with certain blood cancers, a Phase 1 trial sponsored by Mayo Clinic, NCT05549661, is evaluating Onvansertib. This study focuses on recurrent or refractory chronic myelomonocytic leukemia and myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap neoplasms. It aims to determine the best dose and assess the safety and effectiveness of Onvansertib for these conditions, with an enrollment target of 25 patients. Another study, NCT05450965, is a Phase 2 clinical trial investigating Onvansertib for relapsed small cell lung cancer (SCLC). Sponsored by the University of Maryland, Baltimore, this study is recruiting 37 participants who have not responded to or cannot tolerate standard chemotherapy. Onvansertib works by inhibiting polo-like kinase 1 (PLK-1), an enzyme often over-expressed in SCLC. Finally, the OHSU Knight Cancer Institute is sponsoring an Early Phase 1 trial, NCT04005690, which includes Onvansertib as one of several targeted therapies being studied in patients with various stages of pancreatic cancer. This trial, with an enrollment goal of 90 participants, aims to understand how these different agents work at a molecular level.Where to Participate
Clinical trials for Onvansertib are currently recruiting participants across several locations in the United States, providing opportunities for patients in different regions to access these investigational treatments. The top five cities where these trials are actively enrolling include:- Kansas City, Kansas
- Baltimore, Maryland
- Rochester, Minnesota
- Portland, Oregon
- Pittsburgh, Pennsylvania
Development Timeline
The journey of Onvansertib began with its first clinical trial on October 6, 2017, marking the start of its development. Since then, a total of 13 trials have been initiated, enrolling 612 participants to date. Initially, the development timeline for Onvansertib included studies for conditions such as IBS-C and hyperphosphatemia. However, its focus quickly expanded to a wide range of challenging cancers. Key sponsors like Cardiff Oncology, which has sponsored seven trials, have played a significant role in driving this research. Onvansertib's pipeline has grown to include various forms of pancreatic cancer, such as Stage IV Pancreatic Cancer and Locally Advanced Pancreatic Ductal Adenocarcinoma. Its investigation also expanded into blood cancers like Acute Myeloid Leukemia and Myelodysplastic/Myeloproliferative Neoplasm, and solid tumors including Small-cell Lung Cancer, Colorectal Cancer, and several types of breast cancer, such as Triple Negative Breast Cancer (TNBC). The drug has progressed through various study phases, including Phase 1, Early Phase 1, Phase 1/Phase 2, and six Phase 2 trials, reflecting its ongoing evaluation in diverse cancer settings. The latest trial is projected to conclude by December 17, 2024.