Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06106308 | Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer in Adult Participants With a KRAS or NRAS Mutation | PHASE2 | ACTIVE NOT_RECRUITING | 113 | — | — | Feb 27, 2024 | Jan 1, 2027 | Jan 12, 2026 | 41 | United States |
| NCT03829410 | Onvansertib in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer Patients With a KRAS Mutation | PHASE1 | COMPLETED | 68 | — | — | Jun 24, 2019 | Jan 29, 2024 | Mar 4, 2025 | 7 | United States |
ORR defined as the proportion of participants who achieved a best overall Response (BOR) of CR or PR per RECIST Version 1.1 from randomization until disease progression, or death due to any cause, as determined by blinded independent central review.
DLTs were defined as a Grade 4 hematologic adverse events (AEs), Grade ≥ 3 non-hematologic AEs that were considered related to the study drug and that did not resolve within 14 days following presentation with standard management and care, Grade ≥ 3 thrombocytopenia with bleeding, neutropenic fever, any death not clearly due to the underlying disease or extraneous causes, or any change in liver function that met Hy's Law criteria of a DLT.
AEs were defined as any untoward medical occurrence associated with the use of a drug in humans. TEAEs are defined as any AE that started on or after the first day of study treatment and within 30 days of the last administration of study treatment, or that worsened on or after the first day of study treatment. AE severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 on a scale from Grade 1 (mild) to Grade 5 (death). An AE was considered "serious" if it resulted in death, life-threatening AE, hospitalization or prolongation of hospitalization, persistent or significant incapacity, or congenital anomaly/birth defect. The Investigator determined relatedness to the use of onvansertib. Clinically significant changes in vital signs, laboratory parameters, electrocardiograms, physical examinations, weight, and Eastern Cooperative Oncology Group (ECOG) performance status were reported as AEs.
ORR was defined as the percentage of participants documented to have a confirmed complete response (CR) or partial response (PR) using the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1). Two-sided 95% confidence interval (CI) was calculated using the exact binomial Clopper-Pearson method. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
| Arm | Type | Description |
|---|---|---|
| Onvansertib 20mg + Standard of Care | EXPERIMENTAL | Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI/BEV on Day 1 and Day 15 of each 28-day treatment cycle. |
| Onvansertib 30 mg + Standard of Care (SOC) | EXPERIMENTAL | Participants will receive 30 mg of onvansertib + on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI on Day 1 and Day 15 of each 28-day treatment cycle. |
| Standard of Care (SOC) | ACTIVE_COMPARATOR | Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle. |
| Onvansertib 20 mg + Standard of Care | EXPERIMENTAL | Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle. |
| Onvansertib 30 mg + Standard of Care | EXPERIMENTAL | Participants will receive 30 mg onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle. |
| Standard of Care | ACTIVE_COMPARATOR | Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle. |
| Onvansertib + FOLFIRI + Bevacizumab | EXPERIMENTAL | Phase 1b: Onvansertib escalating starting dose of 12 mg/m\^2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab. This Phase 1b portion of the study has been completed. Phase 2: Onvansertib Recommended Phase 2 Dose (RP2D) of 15 mg/m\^2 orally Day 1 through Day 5 and Day 15 through Day 19 of every 28-day cycle in combination with FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU + 5 mg/kg bevacizumab, with treatment modifications or delays based on unresolved toxicity experienced during a previous cycle. |
| Name | Type | Description |
|---|---|---|
| Onvansertib | DRUG | Oral capsule |
| FOLFIRI | DRUG | FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion |
| Bevacizumab | DRUG | IV Infusion |
| FOLFOX | DRUG | FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion |
Inclusion Criteria: * Histologically confirmed metastatic colorectal cancer. * Documented KRAS or NRAS mutation. * No previous systemic therapy in the metastatic setting. * Participants must be willing to submit archival tissue or undergo fresh biopsy. * Eastern Cooperative Oncology Group (ECOG) pe...