A Study of Botensilimab (AGEN1181) for the Treatment of Advanced Melanoma

NCT05529316 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: C-800-232022-500652-37
• Study Type: interventional
• Target: 150
• Locations: 10 countries
• Sites: 51

Brief Summary

This study is an open-label, 2-part, Phase 2, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetic profiles of botensilimab as monotherapy and in combination with balstilimab in participants with advanced cutaneous melanoma refractory to checkpoint inhibitor therapy.

Conditions

Advanced Melanoma

Keywords

Open-label; Monotherapy; Combination Therapy; Anti-PD-1; Anti-PD-L1; Anti-CTLA-4; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate will be determined using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  First dose through up to 3 months

Secondary Outcomes (4)

• Progression-free Survival

  From first dose to first observation of documented disease progression (or death within 12 weeks of last tumor assessment) (up to 3 months)

• Duration Of Response

  From first dose to first observation of documented disease progression (or death within 12 weeks of last tumor assessment) (up to 3 months)

• Overall Survival Time

  First dose through up to 3 months

• Frequency of Treatment-emergent Adverse Events

  First dose through up to 3 months

Study Arms (4)

Part 1 Cohort A: Botensilimab

EXPERIMENTAL

Participants refractory to PD-(L)1 therapy will receive botensilimab intravenously (IV).

Drug: Botensilimab

Part 1 Cohort B: Botensilimab

EXPERIMENTAL

Participants refractory to PD-(L)1 and anti-CTLA-4 therapies will receive botensilimab IV.

Drug: Botensilimab

Part 2 Cohort A: Botensilimab + Balstilimab

EXPERIMENTAL

Participants refractory to PD-(L)1 will receive botensilimab IV in combination with balstilimab IV.

Drug: Botensilimab; Drug: Balstilimab

Part 2 Cohort B: Botensilimab + Balstilimab

EXPERIMENTAL

Participants refractory to PD-(L)1 and CTLA-4 will receive botensilimab IV in combination with balstilimab IV.

Drug: Botensilimab; Drug: Balstilimab

Interventions

Botensilimab DRUG

An anti-CTLA-4 monoclonal antibody

Also known as: AGEN1181

Part 1 Cohort A: Botensilimab; Part 1 Cohort B: Botensilimab; Part 2 Cohort A: Botensilimab + Balstilimab; Part 2 Cohort B: Botensilimab + Balstilimab

Balstilimab DRUG

An anti-PD-1 monoclonal antibody

Also known as: AGEN2034

Part 2 Cohort A: Botensilimab + Balstilimab; Part 2 Cohort B: Botensilimab + Balstilimab

Eligibility Criteria

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

You may qualify if:

• Cohort A only:
• Prior treatment with anti-PD-(L)1 therapy (for example, pembrolizumab or nivolumab) for at least 6 weeks and radiologic progression confirmed by 2 scans at least 4 weeks apart, or if symptomatic due to progressive malignancy, then 1 scan showing progression is sufficient.
• Progression must be either on treatment with anti-PD-(L)1 regimen or ≤ 12 weeks from last anti-PD-(L)1 dose in metastatic setting or ≤ 24 weeks from completion of therapy in adjuvant/ neoadjuvant setting.
• For Part 2 only, no intervening anti-cancer therapy between the last course of anti-PD-(L)1 treatment and the first dose of study treatment except for local measures (for example, surgical excision, biopsy, focal radiation therapy), or BRAF ± MEK inhibition when applicable in BRAF mutant participants.
• Cohort B only:
• Prior treatment with first-generation anti-CTLA-4 therapy (for example, ipilimumab or tremelimumab) and prior treatment with anti-PD-(L)1 for at least 6 weeks.
• Progression on most recent anti-cancer therapy.
• For Part 2 only, no more than 3 prior lines of therapy in the advanced setting for BRAF mutant and no more than 2 prior lines of therapy in the advanced setting in the BRAF wild type.
• Cohorts A and B:
• Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
• Histologically confirmed Stage III (unresectable) or Stage IV histologically confirmed cutaneous melanoma as per the American Joint Committee on Cancer 8th edition staging system.
• Measurable disease on baseline imaging per RECIST 1.1 criteria.
• BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the screening period.
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group performance status of 0 or 1.

You may not qualify if:

• Cohort A:
• \. Received prior anti-CTLA-4 therapy.
• Cohort B:
• \. Received prior Fc-engineered or Fc-enhanced anti-CTLA-4 therapy (for example, BMS-96218, BMS-986288, HBM4003, XTX101, CTLA-4 targeting bispecific or other approaches such as ONC-392).
• Cohorts A and B:
• Ocular, uveal, or mucosal melanoma.
• Any persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≥ 2) from prior cancer therapy, excluding endocrinopathies stable on medication, stable neuropathy, and alopecia.
• Any history of CTCAE Grade ≥ 3 immune-mediated toxicity (excluding endocrinopathies and non-necrotizing/bullous rash) from prior checkpoint inhibitor therapy that required treatment with systemic corticosteroids (\> 10 mg/day prednisone or equivalent) or other immunosuppressive medications for more than 4 weeks.
• Refractory ascites require 2 or more therapeutic paracentesis in the last 4 weeks or ≥ 4 within the last 90 days prior to study entry.
• Bowel obstruction within the past 3 months or an impending bowel obstruction.
• 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 ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.
• Active brain metastases or leptomeningeal metastases with the following exceptions:
• Treated brain metastases require a) surgical resection, or b) stereotactic radiosurgery. These participants must be off steroids ≥ 10 days prior to randomization for the purpose of managing their brain metastases. Repeat brain imaging following surgical resection or stereotactic radiosurgery is not required if their last brain magnetic resonance imaging is within screening window. Whole-brain radiation is not allowed.
• Untreated isolated brain metastases that are too small for treatment by surgical resection or stereotactic radiosurgery (for example, 1-2 millimeters) and/or of uncertain etiology are potentially eligible but need to be discussed with and approved by the study Medical Monitor.
• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment (that is, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the participant has no evidence of disease). Participants with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (51)

Scottsdale Healthcare Hospitals DBA HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Virginia K. Crosson Cancer Center at St. Jude Medical Center

Fullerton, California, 92835, United States

Location

Providence Saint John's Health Center

Santa Monica, California, 90404, United States

Location

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20057, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Universitair Ziekenhuis Brussel

Jette, 1090, Belgium

Location

Oncosite - Centro de Pesquisa Clinica Em Oncologia

Ijuí, 98700-000, Brazil

Location

Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

Jaú, 17210-080, Brazil

Location

Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, 90110-270, Brazil

Location

INCA II - Instituto Nacional de Cancer Jose Alencar Gomes da Silva

Rio de Janeiro, 20220-410, Brazil

Location

Hospital Sirio Libanes

São Paulo, 01308-050, Brazil

Location

Real e Benemerita Associaçao Portuguesa de Beneficencia - A Beneficencia Portuguesa de Sao Paulo

São Paulo, 01323-001, Brazil

Location

Hospital A.C. Camargo Cancer Center

São Paulo, 01509-010, Brazil

Location

CHU Amiens Picardie - Hopital Sud

Amiens, 80054, France

Location

CHU Grenoble-Alpes - Hopital Michallon

La Tronche, 38700, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

CHU de Nantes

Nantes, 44093, France

Location

AP-HP Hopital Saint-Louis

Paris, 75010, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Gustave Roussy

Villejuif, France

Location

Universitaetsklinikum Essen

Essen, 45122, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

University Hospital Schleswig-Holstein

Kiel, 24105, Germany

Location

Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz

Mainz, 55131, Germany

Location

Klinikum der Universitaet München

München, 80377, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Würzburg

Würzburg, 97080, Germany

Location

IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l.

Meldola, 47014, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, 80131, Italy

Location

Azienda Ospedaliero Universitaria Senese

Siena, 53100, Italy

Location

Blokhin National Medical Research Oncology Centre

Moscow, 115478, Russia

Location

Branch Office of "Hadassah Medical Ltd"

Moscow, 121205, Russia

Location

Moscow City Oncology Hospital #62

Moscow, 143423, Russia

Location

LLC Medical Services

Saint Petersburg, 194356, Russia

Location

Clinical Hospital Russian Railways - Medicine

Saint Petersburg, 195271, Russia

Location

Petrov National Medical Research Center of Oncology

Saint Petersburg, 197758, Russia

Location

Hospital Universitario Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 8036, Spain

Location

Onkologikoa

Donostia / San Sebastian, 20014, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

CHUV - Centre hospitalier universitaire vaudois

Lausanne, 1011, Switzerland

Location

Universitaetsspital Zuerich

Zurich, CH-8091, Switzerland

Location

Royal Marsden Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Mount Vernon Cancer Centre

Middlesex, HA6 2RN, United Kingdom

Location

MeSH Terms

Interventions

balstilimab

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 7, 2022
• Study Start: December 12, 2022
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

BE (1); US (7); DE (8); FR (7); IT (3); RU (6); ES (7); GB (3); BR (7); CH (2)