A Phase 1 Study Investigating AGEN1571 as a Single Agent and in Combination With a PD-1 Inhibitor and/or Botensilimab (AGEN1181) in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Agenus Inc.
- Enrollment
- 22
- Locations
- 6
- Primary Endpoint
- Number Of Participants With Treatment-emergent Adverse Events
Overview
Brief Summary
This is an open-label, Phase 1, 2-part trial to determine recommended phase 2 doses (RP2Ds) and evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of AGEN1571 both as a monotherapy and in combination with balstilimab (PD-1 inhibitor) and/or botensilimab (2-agent combination or 3-agent combination) in participants diagnosed with advanced solid tumors.
Part 1 will be the dose escalation phase to determine the RP2D of AGEN1571 monotherapy or AGEN1571 in combination with balstilimab and/or botensilimab. Part 2 will be the dose expansion phase for specific disease indications. Participants will receive study treatment for up to 2 years, or until any disease progression, unacceptable toxicity, or participant wishes to withdraw consent for any reason.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures (participation in genetic testing is optional).
- •Histologically confirmed diagnosis of a solid tumor that is currently metastatic or locally advanced for which no standard therapy is available or standard therapy has failed.
- •Measurable disease on baseline imaging based on RECIST 1.
- •Life expectancy of at least 3 months.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Adequate organ and bone marrow reserve function, as indicated by the following laboratory values:
- •Adequate hematological function, defined as absolute neutrophil count ≥ 1.5 × 10\^9/liter (L), platelet count ≥ 100 × 10\^9/L, and hemoglobin ≥ 8 grams (g)/deciliter (dL) without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement).
- •Adequate liver function, defined as serum albumin ≥ 3.0 g/dL, total bilirubin level ≤ 1.5 × institutional upper limit of normal (IULN), aspartate aminotransferase ≤ 2.5 × IULN, and alanine aminotransferase ≤ 2.5 × IULN, and alkaline phosphatase ≤ 2.5 × IULN or ≤ 5 × IULN for participants with liver metastases.
- •Adequate renal function defined as calculated creatinine clearance ≥ 40 milliliters/minute as assessed by Cockcroft-Gault method.
- •Adequate coagulation, defined as international normalized ratio or prothrombin time ≤ 1.5 × IULN and activated partial thromboplastin time ≤ 1.5 × IULN (unless participant is receiving anticoagulant therapy).
Exclusion Criteria
- •Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of first dose of current study drug.
- •Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery outside of the acceptable washout periods prior to first dose of study drug. The following washout windows are acceptable from prior treatments, that is participants with time periods less than the following should be excluded:
- •Cytotoxic agent or monoclonal antibody ≥ 3 weeks is acceptable (that is, \< 3 weeks should be excluded).
- •A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease.
- •Small molecule targeted investigational therapies and tyrosine kinase inhibitors ≥ 14 days or 5 half-lives is acceptable (that is, \< 14 days or \< 5 half-lives should be excluded).
- •Having a previous severe acute respiratory syndrome coronavirus 2 vaccine \> 7 days before administration is acceptable. For vaccines requiring more than 1 dose, the full series should be completed prior to Cycle 1 Day 1 (C1D1), when feasible, and when the delay in initiation of study treatment would not put the study participants at risk.
- •Prior radiation therapy to the CNS within 2 weeks before first treatment.
- •Persistent toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 Grade \>1 severity that is related to prior therapy.
- •a. Sensory neuropathy or alopecia of Grade ≤ 2 is acceptable. Stable, compensated endocrinopathies (hypothyroidism, adrenal insufficiency, hypophysitis) that are the sequelae of immune-mediated adverse events \> Grade 1 are acceptable.
- •Known severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal antibodies, or to any study drug excipients, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with steroids; or has a history of or active interstitial lung disease, any history of anaphylaxis, or uncontrolled asthma.
Arms & Interventions
Dose Escalation: AGEN1571
Participants will receive AGEN1571 monotherapy.
Intervention: AGEN1571 (Drug)
Dose Escalation: AGEN1571 + Balstilimab
Participants will receive AGEN1571 with balstilimab.
Intervention: AGEN1571 (Drug)
Dose Escalation: AGEN1571 + Balstilimab
Participants will receive AGEN1571 with balstilimab.
Intervention: Balstilimab (Drug)
Dose Escalation: AGEN1571 + Botensilimab
Participants will receive AGEN1571 with botensilimab.
Intervention: AGEN1571 (Drug)
Dose Escalation: AGEN1571 + Botensilimab
Participants will receive AGEN1571 with botensilimab.
Intervention: Botensilimab (Drug)
Dose Escalation: AGEN1571 + Balstilimab + Botensilimab
Participants will receive AGEN1571 with balstilimab and botensilimab.
Intervention: AGEN1571 (Drug)
Dose Escalation: AGEN1571 + Balstilimab + Botensilimab
Participants will receive AGEN1571 with balstilimab and botensilimab.
Intervention: Balstilimab (Drug)
Dose Escalation: AGEN1571 + Balstilimab + Botensilimab
Participants will receive AGEN1571 with balstilimab and botensilimab.
Intervention: Botensilimab (Drug)
Dose Expansion
AGEN1571 administered at the RP2D for monotherapy or any combination therapy.
Intervention: AGEN1571 (Drug)
Dose Expansion
AGEN1571 administered at the RP2D for monotherapy or any combination therapy.
Intervention: Balstilimab (Drug)
Dose Expansion
AGEN1571 administered at the RP2D for monotherapy or any combination therapy.
Intervention: Botensilimab (Drug)
Outcomes
Primary Outcomes
Number Of Participants With Treatment-emergent Adverse Events
Time Frame: Day 1 up to 12 months after the last dose
Number Of Participants With Dose-limiting Toxicities
Time Frame: Day 1 through Day 42
Secondary Outcomes
- Serum Botensilimab Concentration(Day 1 up to 90 days after the last dose)
- Serum AGEN1571 Concentration(Day 1 up to 90 days after the last dose)
- Serum Balstilimab Concentration(Day 1 up to 90 days after the last dose)
- Overall Response Rate (ORR)(Day 1 up to 90 days after the last dose)
- Partial Response (PR) Rate(Day 1 up to 90 days after the last dose)
- Disease Control Rate (DCR)(Day 1 up to 90 days after the last dose)
- Progression-free Survival (PFS)(Day 1 up to 90 days after the last dose)
- Number Of Participants With Anti-drug Antibodies(Day 1 up to 90 days after the last dose)
- Complete Response (CR) Rate(Day 1 up to 90 days after the last dose)
- Duration Of Response (DOR)(Day 1 up to 90 days after the last dose)