2022-502065-23-00
Active, not recruiting
Phase 2
A Randomized, Open-label, Phase 2 study of Botensilimab (AGEN1181) as Monotherapy and in Combination with Balstilimab (AGEN2034) or Investigator’s Choice Standard of Care (Regorafenib or Trifluridine and Tipiracil) for the Treatment of Refractory Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Agenus Inc.
- Enrollment
- 102
- Locations
- 13
- Primary Endpoint
- ORR, defined as the proportion of patients with a complete response or partial response as assessed by RECIST 1.1 criteria.
Overview
Brief Summary
To evaluate the clinical efficacy of botensilimab as monotherapy and in combination with balstilimab through objective response rate (ORR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in the Intent-to-Treat (ITT) Analysis Set.
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Histologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma
- •Measurable disease on baseline imaging per RECIST 1.
- •Life expectancy ≥ 12 weeks
- •ECOG performance status of 0 or
- •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.
- •No growth factor support, transfusions, or albumin administration within 14 days of randomization of study treatment
- •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.
- •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).
- •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 (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). Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
- •Willing and able to comply with the requirements of the protocol.
Exclusion Criteria
- •Tumor is MSI-H/dMMR per a standard local testing method.
- •Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1
- •Received PD-1, PD-L1, or CTLA-4 therapy including any ICI or experimental or immunologic agents
- •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
- •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
- •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
- •Has urine protein ≥1 gram/24 hour.
- •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).
- •Patients who require treatment with strong CYP3A4 inducers or inhibitors
- •Has presence of gastrointestinal condition, e.g., malabsorption, that might affect the absorption of study drug.
Outcomes
Primary Outcomes
ORR, defined as the proportion of patients with a complete response or partial response as assessed by RECIST 1.1 criteria.
ORR, defined as the proportion of patients with a complete response or partial response as assessed by RECIST 1.1 criteria.
Secondary Outcomes
- 01. DOR, defined as the time from initial objective radiographic response until disease progression or death, whichever occurs first.
- 02. PFS, defined as the time from randomization until disease progression or death, whichever occurs first.
- 03. OS, defined as the time from randomization until death due to any cause.
Investigators
Agenus, Inc. Clinical Trial Information
Scientific
Agenus Inc.
Study Sites (13)
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