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

NCT04599140 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2019-1151NCI-2020-07989
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the side effects and best dose of SX-682 that can be given alone and in combination with nivolumab in treating patients with RAS-Mutated, microsatellite stable (MSS) colorectal cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). SX-682 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving SX-682 alone and together with nivolumab may kill more tumor cells.

Conditions

Metastatic Colon Adenocarcinoma; Metastatic Colorectal Carcinoma; Metastatic Rectal Adenocarcinoma; Stage III Colon Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IIIA Colon Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Colon Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Colon Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8; Stage IV Colon Cancer AJCC v8; Stage IV Rectal Cancer AJCC v8; Stage IVA Colon Cancer AJCC v8; Stage IVA Rectal Cancer AJCC v8; Stage IVB Colon Cancer AJCC v8; Stage IVB Rectal Cancer AJCC v8; Stage IVC Colon Cancer AJCC v8; Stage IVC Rectal Cancer AJCC v8; Unresectable Colon Adenocarcinoma; Unresectable Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  For each system organ class and preferred term, summaries will be made with respect to the number and proportion of subjects having at least 1 occurrence of an adverse event during the study. The incidence of AEs will be presented overall, by system organ class and preferred term, intensity (based on National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0), immune-related adverse events, treatment-emergent adverse events, and additional grouping by severity and relationship to study drug. Individual listings of adverse events will be provided. Dose limiting toxicities and study drug-related grade \>= 2 adverse events will be listed individually.

  Up to 2 years

Secondary Outcomes (3)

• Overall response rate (ORR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 104 weeks

• Overall survival (OS)

  Up to 104 weeks

Other Outcomes (1)

• Biomarker analysis

  Up to 2 years

Study Arms (1)

Treatment (SX-682, nivolumab)

EXPERIMENTAL

MONOTHERAPY STAGE: Patients receive SX-682 orally PO BID on days 1-21 in the absence of disease progression or unacceptable toxicity. COMBINATION STAGE: Patients receive SX-682 PO BID on days 1-56 and nivolumab IV over 30 minutes on days 1 and 29. Treatment repeat every 56 days weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: CXCR1/2 Inhibitor SX-682; Biological: Nivolumab

Interventions

CXCR1/2 Inhibitor SX-682 DRUG

Given PO

Also known as: SX 682, SX-682, SX682

Treatment (SX-682, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (SX-682, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent and HIPAA Authorization
• Subjects must have the nature of the study explained to them.
• 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).
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, pharmacokinetic collections, and other requirements of the study.
• 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.
• Subjects must provide a signed and dated Health Insurance Portability and Accountability Act (HIPAA) authorization.
• The ICF and HIPAA authorization must be obtained before conducting any procedures that do not form a part of the subject's normal care.

You may not qualify if:

• Target Population
• 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.
• Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum that is metastatic or unresectable.
• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 1).
• Must have measurable disease with at least 1 unidimensional measurable lesion per RECIST v1.1 (see Appendix 2).
• Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration.
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to first dose:
• WBC \> 3000/µL Neutrophils \> 1500/ µL Platelets \> 100,000/µL Hemoglobin \> 9.0 g/dL (may have been transfused) Creatinine \< 1.5 mg/dL AST/ALT \< 2.5 X ULN for subject with no liver metastases \< 5 X ULN for subjects with liver metastases Bilirubin \< 1.5 mg/dL (unless diagnosed with Gilbert's syndrome, who can have total bilirubin \< 3.0 mg/dL) INR or PT \< 1.5 X ULN unless the subject is receiving anticoagulant therapy aPTT or PTT \< 1.5 X ULN unless the subject is receiving anticoagulant therapy
• Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula \>60 ml/min.
• Life expectancy \> 12 weeks as judged by the treating physician.
• 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.
• Target Disease Exceptions

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• Syntrix Biosystems, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Rectal Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alisha Bent, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: October 22, 2020
• Study Start: October 14, 2020
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (1)