Study of AGEN1571 in Participants With Advanced Solid Tumors

Sponsor

Agenus Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05377528

Collaborator

(none)

Enrollment

Locations

Arms

70.4

Anticipated Duration (Months)

19.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, Phase 1, 2-part study to determine the recommended phase 2 dose (RP2D) and evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of AGEN1571 both as a monotherapy and in combination with balstilimab 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Drug: AGEN1571 Drug: Balstilimab Drug: Botensilimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

98 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 19, 2022

Anticipated Primary Completion Date :

Jun 1, 2028

Anticipated Study Completion Date :

Jun 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation: AGEN1571 Participants will receive AGEN1571 monotherapy.	Drug: AGEN1571 A fully human monoclonal immunoglobulin-like transcript antagonist antibody administered intravenously.
Experimental: Dose Escalation: AGEN1571 + Balstilimab Participants will receive AGEN1571 with balstilimab.	Drug: AGEN1571 A fully human monoclonal immunoglobulin-like transcript antagonist antibody administered intravenously. Drug: Balstilimab A fully human monoclonal programmed cell death protein 1 antagonist antibody administered intravenously.
Experimental: Dose Escalation: AGEN1571 + Botensilimab Participants will receive AGEN1571 with botensilimab.	Drug: AGEN1571 A fully human monoclonal immunoglobulin-like transcript antagonist antibody administered intravenously. Drug: Botensilimab A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.
Experimental: Dose Escalation: AGEN1571 + Balstilimab + Botensilimab Participants will receive AGEN1571 with balstilimab and botensilimab.	Drug: AGEN1571 A fully human monoclonal immunoglobulin-like transcript antagonist antibody administered intravenously. Drug: Balstilimab A fully human monoclonal programmed cell death protein 1 antagonist antibody administered intravenously. Drug: Botensilimab A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.
Experimental: Dose Expansion AGEN1571 administered at the RP2D for monotherapy or any combination therapy.	Drug: AGEN1571 A fully human monoclonal immunoglobulin-like transcript antagonist antibody administered intravenously. Drug: Balstilimab A fully human monoclonal programmed cell death protein 1 antagonist antibody administered intravenously. Drug: Botensilimab A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.

Outcome Measures

Primary Outcome Measures

Number Of Participants With Dose-limiting Toxicities [Day 1 through Day 42]
Number Of Participants With Treatment-emergent Adverse Events [Day 1 up to 12 months after the last dose]

Secondary Outcome Measures

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]
Serum Botensilimab Concentration [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 [Day 1 up to 90 days after the last dose]
Complete response will be determined using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Partial Response [Day 1 up to 90 days after the last dose]
Partial response will be determined using RECIST 1.1.
Duration Of Response [Day 1 up to 90 days after the last dose]
Duration of response will be determined using RECIST 1.1.
Stable Disease [Day 1 up to 90 days after the last dose]
Stable disease will be determined using RECIST 1.1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 1.1.
Life expectancy of at least 3 months.
Eastern Cooperative Oncology Group performance status of 0 or 1.
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 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 × ULN 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).
Participants with a history of prior malignancy are eligible if treatment was completed ≥2 years prior to the first dose of study treatment and the participant has no evidence of disease. Participants with a history of prior early-stage basal/squamous cell skin cancer, or noninvasive or in situ cancers, who have undergone definitive treatment at any time are also eligible.
Participants must provide a sufficient and adequate formalin-fixed paraffin embedded tumor tissue sample (fresh biopsy) collected within 28 days before the first dose from a site not previously irradiated and agree to a mandatory on-treatment biopsy, if clinically feasible. If a potential study participant cannot provide a tumor tissue sample as specified above, enrollment may be possible following discussion and approval from the Medical Monitor.
Female participants of childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study medication) with repeat urine or serum pregnancy test of Day 1 of each cycle and at the end of treatment visit. Non-childbearing potential is defined as:
≥50 years of age and has not had menses for greater than 1 year.
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.
Status is post hysterectomy, bilateral oophorectomy, or tubal ligation.

Female participants who are diagnosed with a tumor that is known to secrete human chorionic gonadotropin must be certified not pregnant based on clinical evidence and investigator judgment.

Female participants of child-bearing potential must agree to use highly effective contraceptive measures starting with the screening visit through 90 days after the last dose of study treatment.

Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.

Male participants 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 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.

Willing and able to comply with the requirements of the protocol.

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.
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 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.

Sensory neuropathy or alopecia of Grade ≤2 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.
Participants with a condition requiring systemic treatment with either corticosteroids (>10 milligrams [mg] daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses (≤10 mg daily prednisone equivalent), are permitted in the absence of active autoimmune disease.
Participants are eligible if CNS metastases have been treated and participants are radiologically and clinically stable. Participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone or equivalent for at least 2 weeks prior to the first dose of study treatment.
Active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study drug (that is with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Participants with autoimmune conditions requiring hormone replacement therapy or topical treatments are eligible.
Has had an allogeneic tissue/solid organ transplant, except for corneal transplants.
An active infection requiring treatment within 2 weeks of C1D1, or active interstitial lung disease.
Human immunodeficiency virus (HIV) positive.
Participants with cluster of differentiation 4 >200 cells/cubic millimeter are eligible.
Participants with HIV viral load undetectable are eligible.
Active hepatitis B (HBV) or active hepatitis C (HCV).
Participants with HBV infection are eligible if HBV surface antigen and HBV DNA are negative.
Participants with HCV infection are eligible if HCV RNA is negative.
Clinically significant (that is active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥II), or serious uncontrolled cardiac arrhythmia requiring medication.
History or current evidence of any condition (including psychiatric or substance abuse disorder that would interfere with the cooperation with the requirements of the trial), therapy, any active infection requiring treatment within 2 weeks of C1D1, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
Legally incapacitated or has limited legal capacity.
Pregnant or breastfeeding.
Corrected QT interval (QTc) >480 milliseconds at screening except if the prolonged QTc is due to right bundle branch block.
Uncontrolled hypertension and controlled hypertension (>140/90 millimeters of mercury) on more than 3 antihypertensive agents.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
3	Florida Cancer Specialists	Sarasota	Florida	United States	34232
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Lifespan Cancer Institute	Providence	Rhode Island	United States	02903