Onvansertib in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer Patients With a KRAS Mutation

Inclusion Criteria

• Histologically confirmed metastatic and unresectable colorectal cancer (CRC).
• Documentation of a KRAS mutation in exon 2, 3 or 4 in primary tumor or metastasis, assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Participants with concomitant KRAS and BRAF-V600 mutations are excluded from this study. Participants with Microsatellite Instability High/Deficient Mismatch Repair (MSI-H/ddMMR) are also ineligible for enrollment in this study.
• Formalin-fixed, paraffin-embedded (FFPE) tumor tissue must be available for submission to a central laboratory in order for a participant to be eligible. If no archival tissue biopsy is available the participant must have a biopsy obtained at screening.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Signed informed consent for participation in the study.
• Participant is not receiving any other standard-of-care or experimental cancer therapy. Participants participating in non-interventional surveys or observational studies are allowed.
• Has failed treatment or is intolerant of fluoropyrimidine and oxaliplatin with or without bevacizumab.
• Participants must have had systemic therapy within 180 days of the screening visit, but can have no anti-cancer therapy within 28 days of the planned first day of treatment on study.
• Participants must have received oxaliplatin based chemotherapy with or without bevacizumab (>6 weeks in duration). Participants who received maintenance therapy with fluoropyrimidines are eligible with or without re-challenge with oxaliplatin in combination with fluoropyrimidines.
• Participants who received oxaliplatin/fluoropyrimidine-based neoadjuvant or adjuvant therapy and have disease recurrence or progression > 6 months from their last dose of neoadjuvant or adjuvant treatment (or > 6 months from surgery if no adjuvant therapy was administered) will be required to have received fluoropyrimidine/oxaliplatin-based therapy with or without bevacizumab as first-line treatment for metastatic disease.
• Participants must not have received prior irinotecan.
• For participants with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen for advanced disease.
• Participants who discontinued first-line therapy because of toxicity are eligible for as long as progression occurred 12 consecutive months); or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device (IUD) or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child-bearing potential.
• Imaging computed tomography (CT)/ magnetic resonance imaging (MRI) of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 21 days prior to enrollment. Only participant with measurable disease as defined per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) are eligible for enrollment. CT is the preferred imaging modality, but MRI is also accepted.
• Must have acceptable organ function.
• Participant must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative, formalin fixed, paraffin block of tumor tissue to be used for correlative marker assays. Submission of the tissue does not have to occur prior to enrollment.
• Signed informed consent to provide blood sample(s) for specific correlative assays.

Exclusion Criteria

• Concomitant KRAS and BRAF-V600 mutations or MSI-H/dMMR
• Anti-cancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug. The exception is a single dose of radiation up to 8 Gray (equal to 800