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

• ClinicalTrials.gov Identifier: NCT06106308
• Recruitment Status: Recruiting
• First Posted: October 30, 2023
• Last Update Posted: May 3, 2024
• Sponsor: Cardiff Oncology
• Collaborator: Pfizer
• Information provided by (Responsible Party): Cardiff Oncology

Tracking Information

• First Submitted Date: October 24, 2023
• First Posted Date: October 30, 2023
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: February 27, 2024
• Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 24, 2023)

Objective Response Rate (ORR) [ Time Frame: Up to approximately 1 year ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 24, 2023)

• Progression Free Survival (PFS) [ Time Frame: Up to approximately 1 year ]
  PFS defined as the time from the date of randomization to the earliest documented disease progression per RECIST version 1.1, or death due to any cause, as determined by blinded independent central review.
• Duration of Response (DOR) [ Time Frame: Up to approximately 1 year ]
  DOR defined as the time from the date of first documentation of objective tumor response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause, as determined by blinded independent central review.
• Number of Participants with an Adverse Event (AE) [ Time Frame: Up to approximately 1 year ]
  Type, incidence, causality and severity of AEs based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Clinically significant changes from baseline in vital signs, laboratory parameters, electrocardiograms (ECGs), weight, and Eastern Cooperative Oncology Group (ECOG) performance status will be recorded as AEs.
• Disease Control Rate (DCR) [ Time Frame: Up to approximately 1 year ]
  DCR defined as CR plus PR plus stable disease (SD), as determined by independent central review.
• Overall Survival (OS) [ Time Frame: Up to approximately 1 year ]
  OS defined as the time from drug administration to death due to any cause.
• Overall Response (OR) [ Time Frame: Up to approximately 1 year ]
  Defined as CR or PR, PFS, DCR, DOR, and OS associated with a reduction in circulating tumor DNA (ctDNA) mutation allele frequency (MAF).
• Maximum Concentration (Cmax) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab [ Time Frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days) ]
• Area Under the Plasma Concentration Curve (AUC) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab [ Time Frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days) ]
• Trough Concentration (Ctrough) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab [ Time Frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days) ]
• Efficacy: Exposure Response Evaluation of Onvansertib [ Time Frame: Up to approximately 1 year ]
• Safety: Exposure Response Evaluation of Onvansertib [ Time Frame: Up to approximately 1 year ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase 2, Randomized, Open-label 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 Patients With a KRAS or NRAS Mutation
• Brief Summary: The purpose of this study is to assess 2 different doses of onvansertib to select the lowest dose that is maximally effective, and to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of onvansertib in combination with FOLFIRI + bevacizumab or FOLFOX + bevacizumab in patients with KRAS or NRAS-mutated metastatic colorectal cancer (CRC) in the first-line setting.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Colorectal Cancer
• CRC
• KRAS/NRAS Mutation

Intervention

• Drug: Onvansertib
  Oral capsule
• Drug: FOLFIRI
  FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
• Drug: Bevacizumab
  IV Infusion
• Drug: FOLFOX
  FOLFOX (leucovorin + fluorouracil [5-FU] + oxaliplatin) as intravenous (IV) infusion

Study Arms

• Experimental: Onvansertib 20mg + Standard of Care
  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.
  Interventions:

  • Drug: Onvansertib
  • Drug: FOLFIRI
  • Drug: Bevacizumab
• Experimental: Onvansertib 30 mg + Standard of Care (SOC)
  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.
  Interventions:

  • Drug: Onvansertib
  • Drug: FOLFIRI
  • Drug: Bevacizumab
• Active Comparator: Standard of Care (SOC)
  Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
  Interventions:

  • Drug: FOLFIRI
  • Drug: Bevacizumab
• Experimental: Onvansertib 20 mg + Standard of Care
  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.
  Interventions:

  • Drug: Onvansertib
  • Drug: Bevacizumab
  • Drug: FOLFOX
• Experimental: Onvansertib 30 mg + Standard of Care
  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.
  Interventions:

  • Drug: Onvansertib
  • Drug: Bevacizumab
  • Drug: FOLFOX
• Active Comparator: Standard of Care
  Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
  Interventions:

  • Drug: Bevacizumab
  • Drug: FOLFOX

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 24, 2023): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2027
• Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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) performance status of 0 or 1.
• Women of childbearing potential must use contraception or take measures to avoid pregnancy.
• Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis and other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib.
• Must have acceptable organ function

Exclusion Criteria:

• Concomitant KRAS or NRAS and BRAF-V600 mutation or microsatellite instability high/deficient mismatch repair.
• Prior treatment with a VEGF inhibitor, including bevacizumab or biosimilars.
• Previous oxaliplatin treatment within 12 months prior to randomization, when arm open.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Anticancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug.
• Untreated or symptomatic brain metastasis.
• Gastrointestinal (GI) disorder(s) that would significantly impede the absorption of an oral agent.
• Unable or unwilling to swallow study drug.
• Uncontrolled intercurrent illness.
• Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxalipatin.
• Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
• Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers.
• QTc >470

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nancy Sherman; 858-952-7570; patients@cardiffoncology.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06106308
• Other Study ID Numbers: CRDF-004
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cardiff Oncology
• Original Responsible Party: Same as current
• Current Study Sponsor: Cardiff Oncology
• Original Study Sponsor: Same as current
• Collaborators: Pfizer
• Investigators: Not Provided
• PRS Account: Cardiff Oncology
• Verification Date: May 2024