Clinical study to investigate efficacy of Botensilimab (AGEN1181) as Monotherapy and in Combination with Balstilimab (AGEN2034) or Investigator’s Choice Standard of Care in patients of Refractory Metastatic Colorectal Cancer

Phase 1

Recruiting

• Conditions: Refractory Metastatic Colorectal Cancer; MedDRA version: 21.1Level: PTClassification code: 10055114Term: Colon cancer metastatic Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-502065-23-00
• Lead Sponsor: Agenus Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-28
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

01. Histologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma, 06. Measurable disease on baseline imaging per RECIST 1.1., 07. Life expectancy = 12 weeks, 08. ECOG performance status of 0 or 1., 09. Adequate organ function defined as the following laboratory values within 7 days of Cycle 1 Day 1 (C1D1): a. Neutrophils = 1500/µL. b. Platelets = 100 × 103 /µL . c. Hemoglobin = 8.0 g/dL . d. Creatinine clearance = 30 mL/min as measured or calculated per local institutional standards. e. Aspartate aminotransferase/alanine aminotransferase = 2.5 × upper limit of normal (ULN). f. Total bilirubin = 1.5 × ULN (except patients with Gilbert syndrome who must have a total bilirubin level of = 3.0 × ULN). g. Albumin = 3.0 g/dL., 14. No growth factor support, transfusions, or albumin administration within 14 days of randomization of study treatment, 10. The most recent biopsy of a tumor lesion that is available as a formalin-fixed paraffin-embedded (FFPE) tumor tissue block is required. If recent tumor tissue is unavailable or inadequate, patient must be willing to provide a fresh biopsy if deemed safe and feasible. The sponsor may waive the requirement for screening biopsies once a sufficient number has been collected., 11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the screening and prior to study drug administration. Non-childbearing potential is defined as: a. = 50 years of age and has not had menses for greater than 1 year. b. Amenorrheic for = 2 years without a hysterectomy and bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation. c. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation. WOCBP must agree to use highly effective contraceptive measures starting with the Screening Visit through 3 months after the last dose of study treatment (if randomized to monotherapy [Arms C or D] or 5 months after the last dose of study treatment (if randomized to combination therapy [Arms A or B]) or 2 months after the last dose of study treatment (if randomized to Arm E and taking regorafenib) or 6 months after the last dose of study treatment (if randomized to Arm E and taking trifluridine and tipiracil). Highly effective contraception is defined in Appendix B, Guidance on Contraception, or as stipulated in national or local guidelines. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. WOCBP must agree not to donate eggs (ova, oocytes) during the treatment period and for at least 3 months after the last dose of study treatment (if randomized to monotherapy [Arms C or D] or 5 months after the last dose of study treatment (if randomized to combination therapy [Arms A or B]) or 2 months after the last dose of study treatment (if randomized to Arm E and taking regorafenib) or 6 months after the last dose of study treatment (if randomized to Arm E and taking trifluridine and tipiracil)., 12. Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the screening visit through 3 months after the last dose of study treatment (if randomized to monotherapy [Arms C or D] or 5 months after the last dose of study treatment (if randomized to combination therapy [Arms A or B]) or 2 months after the last dose of study treatment (i

Exclusion Criteria

01. Tumor is MSI-H/dMMR per a standard local testing method., 19. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1, 02. Received PD-1, PD-L1, or CTLA-4 therapy including any ICI or experimental or immunologic agents, 20. Uncontrolled infection with human immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required, 21. Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for HBV at screening is not required, 22. Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required, 23. Has urine protein =1 gram/24 hour., 24. Uncontrolled hypertension: systolic pressure = 150 mmHg or diastolic pressure = 90 mmHg on repeated measurements that cannot be managed by standard antihypertension medications = 28 days before the first dose of study drug(s)., 25. Patients who require treatment with strong CYP3A4 inducers or inhibitors, 26. Has presence of gastrointestinal condition, e.g., malabsorption, that might affect the absorption of study drug., 27. Non-healing wound(s)., 10. Treatment with one of the following classes of drugs within the delineated time window prior to C1D1: a.Cytotoxic, targeted therapy or other investigational therapy within 3 weeks. b.Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter. c.Small molecule/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half lives of investigational drug., 28. Symptomatic active bleeding, 03. Received regorafenib or trifluridine-tipiracil as prior therapy(ies), 04. Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction, 05. Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks or = 4 times within the last 90 days or = 1 time within the last 2 weeks prior to study entry or requiring diuretics within 2 weeks of study entry., 06. Liver metastases by CT or MRI. NOTE: Patients with definitively treated liver metastases (this includes surgical resection, including microwave or radiofrequency ablation, or stereotactic body radiation therapy [SBRT], but not Y-90 or chemotherapy alone) may be eligible if they were treated at least 6 months prior to enrollment with no evidence of metastatic disease in the liver on subsequent imaging, however they must be excluded if they have: a.Received > 1 SBRT field to the liver. b.Undergone major hepatic resection (right, extended right, or extended left) and the remnant liver was subject to SBRT. c.Stigmata of hepatic decompensation including a history of variceal bleeding, a history of ascites related to hepatic

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified