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Advanced MelanomaPhase 2NCT05529316

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

A Phase 2 study testing Botensilimab and Balstilimab in people with Advanced Melanoma, run by Agenus Inc. at 51 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Melanoma
What is being tested?
Botensilimab and Balstilimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
51 sitesin 10 countries
Study dates
12 Dec 2022to 27 Apr 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To participate in the study, participants must meet all the following inclusion criteria:
  • 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:
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  • 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.
  • Adequate organ function is defined as the following laboratory values within 14 days of Cycle 1 Day 1 (C1D1):
  • Neutrophils > 1500/microliter (μL) (stable off any growth factor within 4 weeks of first study treatment administration).
  • Platelets > 100 × 10^3/μL (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration).
  • Hemoglobin > 8.0 grams/deciliter (g/dL) (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration).
  • Creatinine clearance ≥ 45 milliliters/minute (measured or calculated using modification of diet in renal disease).
  • Aspartate aminotransferase/alanine aminotransferase < 3.0 × upper limit of normal (ULN).
  • Total bilirubin < 1.5 × ULN, or < 3.0 × ULN for participants with Gilbert syndrome.
  • Albumin ≥ 3.0 g/dL.
  • International normalized ratio or prothrombin time ≤ 1.5 × ULN and activated partial thromboplastin time ≤ 1.5 × ULN (unless participant is receiving anticoagulant therapy).
  • Participant must provide a formalin-fixed paraffin-embedded tumor tissue sample from the most recent biopsy of a tumor lesion, obtained within 90 days from signing informed consent form. If recent tumor tissue is unavailable or inadequate, a fresh biopsy will be required, unless the Sponsor agrees that it is not safe/feasible.
  • Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study medication) and prior to study drug administration. In part 1, WOCBP must agree to use highly effective contraceptive measures starting with the screening visit through 3 months after the last dose of study treatment. In Part 2, WOCBP must agree to use highly effective contraceptive measures starting with the screening visit through 5 months after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.
  • In Part 1, 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 3 months after the last dose of study treatment is received. In Part 2, 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 5 months 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.

Who cannot join

  • To participate in the study, participants must meet none of the following exclusion criteria:
  • Cohort A:
  • 1. Received prior anti-CTLA-4 therapy.
  • Cohort B:
  • 1. 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:
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  • 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.
  • Incomplete resolution of clinically significant adverse events related to most recent therapy/intervention prior to enrollment.
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster < 7 days before C1D1. For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. A booster shot is not required but if given, must be administered > 7 days from C1D1 or > 7 days from future cycle on study.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
  • History of allogeneic organ transplant, stem cell transplant or bone marrow transplant (autologous stem cell transplant > 5 years prior to study enrollment with no evidence of disease are eligible unless lymphopenia Grade > 1 is present).
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • 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.
  • Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting study treatment (that is, with use of disease-modifying agents or immunosuppressive drugs).
  • History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the participants participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
  • A WOCBP who is pregnant or breastfeeding or WOCBP who are not willing to employ effective birth control from screening to 90 days after the last dose of botensilimab (whichever is later).
  • Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
  • Uncontrolled infection with human immunodeficiency virus (HIV). Participants on stable highly active antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 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. Participants 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). Participants 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.
  • Dependence on total parenteral nutrition.

Trial locations and contacts

51 sites in 10 countries.

51 sites in 10 countries

Germany8 sites

  • Universitaetsklinikum Essen

    Essen, 45122

  • Universitaetsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universitaetsklinikum Heidelberg

    Heidelberg, 69120

  • University Hospital Schleswig-Holstein

    Kiel, 24105

  • Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz

    Mainz, 55131

  • Klinikum der Universitaet München

    München, 80377

  • Universitaetsklinikum Tuebingen

    Tübingen, 72076

  • Universitaetsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

United States7 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

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

    Fullerton, California, 92835

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Yale University School of Medicine - Yale Cancer Center

    New Haven, Connecticut, 06520-8028

  • Providence Saint John's Health Center

    Santa Monica, California, 90404

  • Scottsdale Healthcare Hospitals DBA HonorHealth

    Scottsdale, Arizona, 85258

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20057

Other trials in United States

Brazil7 sites

  • Oncosite - Centro de Pesquisa Clinica Em Oncologia

    Ijuí, 98700-000

  • Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

    Jaú, 17210-080

  • Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

    Porto Alegre, 90110-270

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

    Rio de Janeiro, 20220-410

  • Hospital Sirio Libanes

    São Paulo, 01308-050

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

    São Paulo, 01323-001

  • Hospital A.C. Camargo Cancer Center

    São Paulo, 01509-010

Other trials in Brazil

France7 sites

  • CHU Amiens Picardie - Hopital Sud

    Amiens, 80054

  • CHU Grenoble-Alpes - Hopital Michallon

    La Tronche, 38700

  • Centre Leon Berard

    Lyon, 69008

  • CHU de Nantes

    Nantes, 44093

  • AP-HP Hopital Saint-Louis

    Paris, 75010

  • Centre Eugene Marquis

    Rennes, 35042

  • Gustave Roussy

    Villejuif

Other trials in France

Spain7 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 8035

  • Hospital Clinic Barcelona

    Barcelona, 8036

  • Onkologikoa

    Donostia / San Sebastian, 20014

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Consorcio Hospital General Universitario de Valencia

    Valencia, 46014

Other trials in Spain

Russia6 sites

  • Blokhin National Medical Research Oncology Centre

    Moscow, 115478

  • Branch Office of "Hadassah Medical Ltd"

    Moscow, 121205

  • Moscow City Oncology Hospital #62

    Moscow, 143423

  • LLC Medical Services

    Saint Petersburg, 194356

  • Clinical Hospital Russian Railways - Medicine

    Saint Petersburg, 195271

  • Petrov National Medical Research Center of Oncology

    Saint Petersburg, 197758

Other trials in Russia

Italy3 sites

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

    Meldola, 47014

  • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

    Naples, 80131

  • Azienda Ospedaliero Universitaria Senese

    Siena, 53100

Other trials in Italy

United Kingdom3 sites

  • Royal Marsden Foundation Trust

    London, SW3 6JJ

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Mount Vernon Cancer Centre

    Middlesex, HA6 2RN

Other trials in United Kingdom

Switzerland2 sites

  • CHUV - Centre hospitalier universitaire vaudois

    Lausanne, 1011

  • Universitaetsspital Zuerich

    Zurich, CH-8091

Other trials in Switzerland

Belgium1 site

  • Universitair Ziekenhuis Brussel

    Jette, 1090

Other trials in Belgium

About this study

Official title: A Multicohort, Open Label, Phase 2 Study of Botensilimab (AGEN1181) for Treatment of Advanced Melanoma Refractory to Prior Checkpoint Inhibitor Therapy

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.

Read the detailed description

This Phase 2 study will enroll up to approximately 220 evaluable adult participants with a histologically confirmed diagnosis of either Stage III (unresectable) or Stage IV cutaneous melanoma and who have had prior treatments with anti-programmed death (ligand) 1 [PD-(L)1].

This study will consist of 2 parts. Part 1 consists of 2 cohorts (Cohorts A and B) that will receive botensilimab monotherapy. In Cohort A, participants refractory to PD-(L)1 will receive botensilimab. In Cohort B, participants refractory to PD-(L)1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) will receive botensilimab. Part 2 consists of Cohorts A and B that will receive botensilimab combination therapy. In Cohort A, participants refractory to PD-(L)1 will receive botensilimab in combination with balstilimab. In Cohort B, participants refractory to PD-(L)1 and CTLA-4 will receive botensilimab in combination with balstilimab.

Being tested
Botensilimab, Balstilimab
Keywords
Open-label, Monotherapy, Combination Therapy, Anti-PD-1, Anti-PD-L1, Anti-CTLA-4, Immunotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BotensilimabDrug

    Also called AGEN1181

    An anti-CTLA-4 monoclonal antibody

  • BalstilimabDrug

    Also called AGEN2034

    An anti-PD-1 monoclonal antibody

Study groups in NCT05529316
Study groupRoleWhat they receive
Part 1 Cohort A: BotensilimabExperimentalParticipants refractory to PD-(L)1 therapy will receive botensilimab intravenously (IV).
Receives: Drug: Botensilimab
Part 1 Cohort B: BotensilimabExperimentalParticipants refractory to PD-(L)1 and anti-CTLA-4 therapies will receive botensilimab IV.
Receives: Drug: Botensilimab
Part 2 Cohort A: Botensilimab + BalstilimabExperimentalParticipants refractory to PD-(L)1 will receive botensilimab IV in combination with balstilimab IV.
Receives: Drug: Botensilimab; Drug: Balstilimab
Part 2 Cohort B: Botensilimab + BalstilimabExperimentalParticipants refractory to PD-(L)1 and CTLA-4 will receive botensilimab IV in combination with balstilimab IV.
Receives: Drug: Botensilimab; Drug: Balstilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

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

    Measured: Up to 40 months

Secondary outcomes (4)

  1. Progression-free Survival

    Progression-free survival will be determined using RECIST 1.1.

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

  2. Duration Of Response

    Duration of response will be determined using RECIST 1.1.

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

  3. Overall Survival Time

    Overall survival will be quantified as a median.

    Measured: First dose through up to 3 months

  4. Frequency of Treatment-emergent Adverse Events

    Measured: First dose through up to 27 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2022
  2. Study start12 Dec 2022
  3. Primary completion27 Apr 2026
  4. Study completion27 Apr 2026

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05529316
Sponsor's protocol ID
C-800-23
Other IDs
2022-500652-37
Status last verified
Oct 2026
First submitted
2 Sep 2022
Last updated
19 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Botensilimab and Balstilimab in people with Advanced Melanoma, run by Agenus Inc. at 51 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in Germany, United States, Brazil, France, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: Up to 40 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05529316.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.

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