Phase 2 Study of SR-8541A in Combination With Botensilimab and Balstilimab in Subjects With Refractory Metastatic Microsatellite Stable Colorectal Cancer (MSS-CRC)

Trial Title: Phase 2 Study of SR-8541A in Combination With Botensilimab and Balstilimab in Subjects With Refractory Metastatic Microsatellite Stable Colorectal Cancer (MSS-CRC)

NCT ID: NCT06589440

Condition: Refractory Metastatic Microsatellite Stable Colorectal Cancer (MSS-CRC)

Conditions: Official terms:
Colorectal Neoplasms

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention model description: Part 1 will follow a traditional 3+3 dose escalation scheme. Approximately 6-12 subjects will be treated in Part 1. Part 2 Approximately up to 58 subjects will be enrolled: Cohort A: MSS-CRC subject with no active liver metastases Cohort B: MSS-CRC subject with active liver metastases

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: SR-8541A
Description: SR-8541A administered orally in combination with intravenous botensilimab and balstilimab
Arm group label: MSS-CRC subject with active liver metastases
Arm group label: MSS-CRC subject with no active liver metastases

Other name: Botensilimab

Other name: Balstilimab

Summary: This is an open-label, dose escalation and expansion, multi-center phase 2 study evaluating the safety and efficacy of SR-8541A administered orally in combination with intravenous botensilimab and balstilimab in subjects with MSS-CRC with and without active liver metastases.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Written informed consent from subject 2. Age ≥ 18 years old on the date of consent 3. Histologically confirmed diagnosis of unresectable and metastatic adenocarcinoma of the colon or rectum 4. Non-microsatellite instability high or non-deficient mismatch repair (non-MSI-H/non-dMMR) tumor status per a standard local testing method 5. Must have received at least 1 prior chemotherapy regimen for metastatic or recurrent CRC 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 7. Measurable disease per RECIST v1.1 (Eisenhauer et al., 2009) 8. Able to provide archival or fresh tumor tissue during screening (required) and post-treatment (optional) 9. Adequate renal function defined as creatinine clearance ≥ 60mL/min 10. Adequate liver function 11. Adequate hematologic function 12. No growth factor support, transfusions, or albumin administration within 14 days of first dose of study treatment 13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures 14. Male and female subjects of childbearing potential must agree to use a highly medically effective method of contraception and refrain from sperm/egg donation throughout the study starting with the first dose of study treatment (or 14 days prior to the first dose of study treatment for oral contraception) and for at least 3 months after the last dose of study treatment Exclusion Criteria: 1. Hypersensitivity or allergy to any of the study drugs or their excipients. 2. In Part 2, Cohort A, active liver metastases by computed topography (CT) or magnetic resonance imaging (MRI). 3. Treatment with one of the following classes of drugs within the delineated time window prior to first dose: 1. Small molecule/tyrosine kinase inhibitors within 2 weeks 2. Any other systemic therapy for CRC within 3 weeks 3. Received another investigational drug within 30 days or active participation in another clinical trial (follow-up is permitted) 4. Medications/products which are known strong inhibitors or inducers of the CYP enzymes within 5 x T1/2 4. Received programmed cell death protein 1, PD-(L)1, or CTLA-4 therapies including any immune checkpoint inhibitor or experimental immunologic agents. 5. Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction. 6. Refractory ascites. 7. Current evidence of interstitial lung disease (ILD) or pneumonitis, or prior history of ILD or non-infectious pneumonitis requiring glucocorticoids. 8. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 28 days prior to Day 1. 9. Active autoimmune disease that has required systemic treatment in past 2 years 10. Patients with adrenal / pituitary insufficiency 11. History of documented congestive heart failure; unstable angina; poorly controlled hypertension; clinically significant valvular heart disease; high-risk uncontrolled arrhythmias (including sustained ventricular tachycardia); myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within the last 6 months, or Canadian Cardiovascular Society angina class > 2 12. History of allogeneic organ transplant, stem cell transplant, or bone marrow transplant 13. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to first dose 14. Requirement for treatment with strong cytochrome P450 3A4 inducers or inhibitors 15. Presence of gastrointestinal condition, for example, malabsorption, that might affect the absorption of Investigational Product(s). 16. Troponin I > ULN 17. Uncontrolled hypertension 18. Corrected QT interval by Fridericia (QTcF) ≥ 470 ms per the central mean average of triplicate electrocardiograms (ECGs) 19. Left Ventricular Ejection Fraction (LVEF) < 50% using echocardiogram or multigated acquisition (MUGA) 20. Symptomatic uncontrolled central nervous system (CNS) disease requiring treatment with steroids or anti-seizure medications within 2 months prior to Day 1. However, subjects with brain metastases that have been previously treated and are stable based on imaging performed within 2 months of Day 1 following completion of any CNS-directed therapy are allowed 21. Leptomeningeal disease 22. Spinal cord compression not definitively treated with surgery and/or radiation 23. Bleeding diathesis due to underlying medical condition or anticoagulation medication which is unable to be promptly reversed by medical treatment 24. Prior additional malignancy that is progressing or has received treatment the previous 3 years prior to first dose except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast 25. History of uncontrolled seizures, central nervous disorders, substance abuse disorder or psychiatric disability judged by the Investigator to be clinically significant and would interfere with cooperation with requirements of the study 26. Active infection requiring systemic treatment at time of first dose 27. Positive for human immunodeficiency virus (HIV) (HIV antibodies) or active hepatitis B (e.g., HbsAg reactive) or active hepatitis C (e.g., HCV ribonucleic acid [RNA] qualitative) infection with detectable viral load 28. Pregnant or lactating females who plan to nurse a child during or within 3 months of the last dose of study treatment 29. Major surgery within 28 days prior to first dose and/or minor surgery (excluding biopsy) within 7 days prior to first dose. Note: If the subject had major surgery, the subject must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention 30. Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the subject or impair the assessment of study results 31. Planned use of any of the prohibited concomitant medications

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: October 2024

Completion date: September 2027

Lead sponsor:
Agency: Stingray Therapeutics
Agency class: Industry

Source: Stingray Therapeutics

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06589440