Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patients With Advanced Cancer

NCT04121676 | Completed Phase 1 FDA Drug

• 1 other identifier: C-1100-01
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 12

Brief Summary

This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of AGEN2373 as a monotherapy and in combination with botensilimab (also known as AGEN1181), and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.

Conditions

Advanced Cancer

Keywords

Combination Therapy; Anti-CD137; Anti-CTLA-4; Single Agent; Monotherapy; Melanoma; Cutaneous Melanoma; Solid Tumors; Advanced Cancer; Open-Label; Dose Escalation; 4-1BB

Outcome Measures

Primary Outcomes (4)

• Occurrence of Dose Limiting Toxicity (DLT)

  DLT in patient in dose escalation phase

  First 28 days of treatment Q2W and Q4W and First 21 days Q3W

• Frequency of treatment-emergent adverse events (TEAEs)

  According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups

  Screening to 90 days from last dose

• Severity of treatment-emergent adverse events (TEAEs)

  According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups

  Screening to 90 days from last dose

• Duration of treatment-emergent adverse events (TEAEs)

  According to NCI-CTCAE Version 5.0, vital signs (blood pressure, heartrate, and temperature), physical examinations, 12-lead electrocardiogram, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments for all dose groups

  Screening to 90 days from last dose

Secondary Outcomes (15)

• Maximum observed concentration at steady state (Cmax-ss)

  Day 1 of dosing through 90 days from the last dose

• Minimum observed concentration at steady state (Cmin-ss)

  Day 1 of dosing through 90 days from the last dose

• Area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)

  Day 1 of dosing through 90 days from the last dose

• Area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t))

  Day 1 of dosing through 90 days from the last dose

• Area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞))

  Day 1 of dosing through 90 days from the last dose

Study Arms (5)

2-Week Monotherapy with AGEN2373

EXPERIMENTAL

3+3 Dose escalation of AGEN2373 administered by IV.

Drug: AGEN2373

3-Week Monotherapy with AGEN2373

EXPERIMENTAL

3+3 Dose escalation of AGEN2373 administered by IV.

Drug: AGEN2373

4-Week Monotherapy with AGEN2373

EXPERIMENTAL

3+3 Dose escalation of AGEN2373 administered by IV.

Drug: AGEN2373

Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab

EXPERIMENTAL

3+3+3 Dose escalation of AGEN2373. AGEN2373 and botensilimab administered by IV.

Drug: AGEN2373; Drug: Botensilimab

Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab

EXPERIMENTAL

3+3+3 Dose escalation of AGEN2373. AGEN2373 and botensilimab administered by IV.

Drug: AGEN2373; Drug: Botensilimab

Interventions

AGEN2373 DRUG

An Anti-CD137 Monoclonal Antibody

Also known as: Anti-CD137

2-Week Monotherapy with AGEN2373; 3-Week Monotherapy with AGEN2373; 4-Week Monotherapy with AGEN2373; Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab; Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab

Botensilimab DRUG

Anti-CTLA-4 Monoclonal Antibody

Also known as: AGEN1181, Anti-CTLA-4

Combination Therapy with 3-week AGEN2373 Monotherapy Lead-In Combination with 6-week Botensilimab; Combination Therapy with 3-week AGEN2373 in combination with 6-week Botensilimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study specific procedures. Participation in pharmacogenomics testing is optional.
• ≥ 18 years of age.
• Histologically or cytologically 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 imaging based on RECIST 1.1.
• Life expectancy of ≥ 3 months and ECOG 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/L, platelet count ≥ 100 × 10\^9/L, and hemoglobin ≥ 8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement)
• Adequate liver function, defined as total bilirubin level ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase ≤ 2.5 × ULN, and alanine aminotransferase ≤ 2.5 × ULN, albumin ≥ 3 g/dL, and alkaline phosphatase ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastases
• Adequate renal function defined as creatinine ≤ 1.5 × ULN OR measured or calculated creatinine clearance ≥ 40 mL/minute per institutional standard. Assessment methods should be recorded
• Adequate coagulation, defined as international normalized ratio or prothrombin time ≤ 1.5 × ULN and activated partial thromboplastin time ≤ 1.5 × ULN (unless patient is receiving anticoagulant therapy)
• Patients with a history of prior malignancy are eligible if treatment was completed ≥ 2 years prior to the first dose of study treatment and the patient has no evidence of disease.
• Patients must provide a sufficient and adequate formalin-fixed paraffin-embedded tumor tissue sample (biopsy) collected after the last dose of prior anti-cancer therapy and before the first dose of study treatment from a site not previously irradiated and agree to mandatory on-treatment biopsy if clinically feasible.
• Female patients of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as 1 of the following:
• ≥ 45 years of age and has not had menses for \> 1 year
• Amenorrheic for \> 2 years without a hysterectomy and oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon prestudy (screening) evaluation

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of first dose of current study treatment.
• Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery outside of the acceptable washout period prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with Sponsor approval.
• The following washout windows are acceptable from prior treatments (i.e., patients with time periods less than the following should be excluded):
• Cytotoxic agent ≥ 3 weeks is acceptable (i.e., \< 3 weeks should be excluded)
• Monoclonal antibodies ≥ 4 weeks is acceptable (i.e., \< 4 weeks should be excluded)
• Proteasome inhibitors or corticosteroids ≥ 2 weeks is acceptable (i.e., \< 2 weeks should be excluded)
• Small molecule/tyrosine kinase inhibitor within 14 days or less than 5 circulating half-lives of investigational drug
• Having a previous SARS-CoV-2 vaccine \> 7 days before administration. For vaccines requiring more than 1 dose, the full series should be completed prior to Cycle 1 Day 1, when feasible, and when the delay in initiation of study treatment would not put the study patients at risk
• Patients who have received prior anti-CD137 therapy may be enrolled upon agreement with the Sponsor.
• Persistent toxicity of NCI-CTCAE version 5.0 Grade \> 1 severity that is related to prior therapy. Note: Sensory neuropathy or alopecia of Grade ≤ 2 are acceptable.
• Expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
• History of:
• Severe (Grade ≥ 3) hypersensitivity reactions to fully human monoclonal antibodies
• Interstitial lung disease or lung disease which may interfere with the assessment of pneumonitis
• Uncontrolled asthma (i.e., ≥ 3 features of partly controlled asthma)

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (12)

University of Southern California Norris Comprehensive Cancer Center/ Hoag

Los Angeles, California, 90033, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Miami

Coral Gables, Florida, 33146, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Roswell Park Comprehensive Cancer Care

Buffalo, New York, 14203, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15232, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Monitor

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 10, 2019
• Study Start: September 26, 2019
• Primary Completion: February 22, 2024
• Study Completion: November 30, 2024
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

US (12)