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

Phase 2Active Not RecruitingNCT06106308

Cardiff Oncology113 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

113

Conditions

Metastatic Colorectal Cancer CRC KRAS/NRAS Mutation

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

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.

Time frame: Up to approximately 1 year

Secondary Outcomes

Progression Free Survival (PFS)

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.

Time frame: Up to approximately 1 year

Duration of Response (DOR)

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.

Time frame: Up to approximately 1 year

Number of Participants with an Adverse Event (AE)

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.

Time frame: Up to approximately 1 year

Disease Control Rate (DCR)

DCR defined as CR plus PR plus stable disease (SD), as determined by independent central review.

Time frame: Up to approximately 1 year

Overall Survival (OS)

OS defined as the time from drug administration to death due to any cause.

Time frame: Up to approximately 1 year

Overall Response (OR)

Defined as CR or PR, PFS, DCR, DOR, and OS associated with a reduction in circulating tumor DNA (ctDNA) mutation allele frequency (MAF).

Time frame: Up to approximately 1 year

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

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

Overview

Conditions

Interventions

Eligibility

Locations (41)

Outcomes

Primary Outcomes

Secondary Outcomes