Botensilimab for Skin Cancer

Not currently recruiting at 67 trial locations

Overseen By Agenus, Inc. Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Agenus Inc.

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Ocular melanoma, Cardiovascular disease, Active brain metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of botensilimab, an experimental treatment, both alone and with balstilimab, for individuals with advanced skin cancer unresponsive to certain treatments. It aims to assess the effectiveness and safety of these drugs in those with advanced cutaneous melanoma that remains unresponsive to prior therapies. Individuals who have received treatments like pembrolizumab or nivolumab for their skin cancer but continue to experience worsening conditions might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them before starting the study treatment. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that botensilimab is generally safe for humans. In earlier studies, patients with various types of cancer who received botensilimab experienced positive outcomes. Side effects were usually mild to moderate, indicating they were not serious.

Combining botensilimab with balstilimab yielded promising safety results. Reports from a large group of patients with advanced cancer indicated that the treatment was mostly safe. These findings offer a solid understanding of the treatment's safety for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for skin cancer, which often include PD-(L)1 and CTLA-4 inhibitors, Botensilimab stands out with its novel mechanism of action. Researchers are excited about Botensilimab because it targets immune checkpoints differently, potentially offering a new pathway to tackle tumors that are resistant to existing therapies. In combination with Balstilimab, Botensilimab may enhance the immune response more effectively, providing hope for patients who have not responded to traditional immunotherapies. This combination approach aims to reinvigorate the immune system in a way that current options may not, offering a promising alternative for challenging cases.

What evidence suggests that this trial's treatments could be effective for advanced cutaneous melanoma?

Research has shown that botensilimab may help treat cancers that don't respond to current immunotherapy, such as advanced melanoma. In previous studies, patients who didn't benefit from other treatments experienced better outcomes. For instance, about 39% of patients who had undergone multiple treatments were still alive after two years. In this trial, some participants will receive botensilimab alone, while others will receive a combination of botensilimab with balstilimab. Combining botensilimab with balstilimab has demonstrated promising safety and effectiveness, even for patients with hard-to-treat tumors. These findings suggest that botensilimab, either alone or with another drug, could be a promising option for people with advanced skin cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Agenus Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma that didn't respond to checkpoint inhibitor therapy. They must have a life expectancy of at least 3 months, good performance status, and adequate organ function. Participants need confirmed Stage III or IV cutaneous melanoma and may require BRAF V600 mutation testing. Women who can bear children and men with partners who can must use effective birth control.

Inclusion Criteria

You are expected to live for at least 3 more months.

Cohort A: Prior treatment with anti-PD-(L)1 therapy 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.

Cohort A: Prior 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.

Exclusion Criteria

Cohorts A and B: History of allogeneic organ transplant.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive botensilimab monotherapy in two cohorts based on prior therapy resistance

Up to 3 months

Treatment Part 2

Participants receive botensilimab in combination with balstilimab in two cohorts based on prior therapy resistance

Up to 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab

Trial Overview The study tests Botensilimab alone or combined with Balstilimab in patients whose melanoma has progressed despite treatment with anti-PD-(L)1 drugs like ipilimumab. It's an open-label Phase 2 trial assessing the effectiveness, safety, tolerability, and how the body processes these drugs.

How Is the Trial Designed?

Group I: Part 2 Cohort B: Botensilimab + Balstilimab Experimental Treatment 2 Interventions

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

Group II: Part 2 Cohort A: Botensilimab + Balstilimab Experimental Treatment 2 Interventions

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

Group III: Part 1 Cohort B: Botensilimab Experimental Treatment 1 Intervention

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

Group IV: Part 1 Cohort A: Botensilimab Experimental Treatment 1 Intervention

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

Botensilimab is already approved in United States for the following indications:

Approved in United States as Botensilimab for:

• None approved yet; Fast Track designation granted for non-MSI-H colorectal cancer

Who Is Running the Clinical Trial?

Agenus Inc.

Lead Sponsor

Trials

58

Recruited

4,900+

Published Research Related to This Trial

In a 10-year study of 102 melanoma patients, 135 skin adverse events (AEs) were identified, with immune checkpoint blockade (ICB) causing 81 AEs and targeted therapies (TT) causing 54 AEs, highlighting the distinct skin toxicity associated with different treatment types.

The incidence of skin AEs was significantly higher with targeted therapies (18.54%) compared to immune checkpoint blockade (9.64%), and while most AEs were low-grade, 19.21% were classified as severe (Grades 3 or 4), indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous Adverse Events of Systemic Melanoma Treatments: A Retrospective Single-Center Analysis. Kraehenbuehl, L., Schneider, S., Pawlik, L., et al.[2023]

In a study of 107 lung cancer patients treated with PD-1/PD-L1 inhibitors, the most common cutaneous adverse events (CAEs) were mild to moderate, with reactive cutaneous capillary endothelial proliferation being the most frequent at 30.8%.

The median time for CAEs to appear varied depending on the treatment combination, with the earliest onset observed in patients receiving PD-1/PD-L1 inhibitors plus chemotherapy, highlighting the importance of early diagnosis and management of these skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous adverse events in lung cancer patients on the therapy based on PD-1/PD-L1 inhibitors: A prospective observational cohort study. Dang, YC., Kong, QT., Wang, Z., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05529316

NCT05529316 | A Study of Botensilimab (AGEN1181) for ... This study is an open-label, 2-part, Phase 2, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetic profiles of botensilimab

2. investor.agenusbio.com investor.agenusbio.com/news/news-details/2025/Agenus-Reports-39-of-Patients-Alive-at-Two-Years-with-BOTBAL-Across-Multiple-Refractory-Solid-Tumors-at-ESMO-2025/default.aspx

Agenus Reports 39% of Patients Alive at Two-Years with ... Durable survival in heavily pretreated patients, including those who failed prior immunotherapy and with active liver metastases Signals of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02524

Botensilimab (Fc-enhanced anti–cytotoxic lymphocyte ... Trial data suggests that BOT appears to improve efficacy of ICIs in immune-cold tumors, including MSS mCRC and ICI-refractory melanoma and non- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609826/

Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is ... Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy.

5. nature.com nature.com/articles/s41591-024-03083-7

Botensilimab plus balstilimab in relapsed/refractory ... The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with ...

6. targetedonc.com targetedonc.com/view/botensilimab-and-balstilimab-prove-notable-os-in-patients-with-advanced-solid-tumors

Botensilimab and Balstilimab Prove Notable OS in ... The median overall survival (OS) was 17.2 months. At 24 months, 39% of patients were alive.Further, the confirmed overall response rate (ORR) ...