SX-682 and Nivolumab for the Treatment of RAS-Mutated, MSS Unresectable or Metastatic Colorectal Cancer, the STOPTRAFFIC-1 Trial

Eligibility Criteria

• 1. Written Informed Consent and HIPAA Authorization
• 1. Subjects must have the nature of the study explained to them.
• 2. Non-English speaking patients will be eligible for participation with involvement of the MD Anderson Language Assistance department in the informed consent process (per MD Anderson SOP 04_Informed Consent Process).
• 3. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, pharmacokinetic collections, and other requirements of the study.
• 4. Subjects must provide a signed and dated IRB approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines for both the study and exploratory biomarker analyses (e.g., CMS4 and others) on archival tissue.
• 5. Subjects must provide a signed and dated Health Insurance Portability and Accountability Act (HIPAA) authorization.
• 6. The ICF and HIPAA authorization must be obtained before conducting any procedures that do not form a part of the subject's normal care.
• 7. After signing the ICF and HIPAA Authorization, subjects will be evaluated for study eligibility during the Screening Period (no more than 28 days before study drug administration) according to the following further inclusion/
• 2. Target Population
• 1. Men and women, ages \> 18 years of age. Both men and women of all races and ethnic groups, regardless of preferred language, are eligible for this trial.
• 2. Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum that is metastatic or unresectable.
• 3. Tumor is determined to be RAS-mutated (KRAS or NRAS) and microsatellite stable/proficient in mismatch repair, as assessed by IHC and/or PCR/NGS in a CLIA environment.
• 4. Received at least two prior regimens of therapy for unresectable or metastatic CRC including fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Patients who relapse within 6 months of adjuvant chemotherapy composed of oxaliplatin and a fluoropyrimidine will have their adjuvant therapy count as one prior regimen.
• 5. For the expansion cohort, pre-treatment primary tumor tissue (i.e., archived paraffin-embedded) or from an unresectable metastatic site must be available for biomarker analyses. Biopsy should be excisional or core needle. Fine needle aspirates or other cytology samples are insufficient.
• 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 1).
• 7. Must have measurable disease with at least 1 unidimensional measurable lesion per RECIST v1.1 (see Appendix 2).
• 8. Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration.
• 9. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to first dose:
• 10. Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula \>60 ml/min.
• 11. Life expectancy \> 12 weeks as judged by the treating physician.
• 12. Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been treated with SX-682). If re-enrolled, the subject must be re-consented.
• 1. Target Disease Exceptions
• 2. Medical History and Concurrent Diseases