Botensilimab for Skin Cancer

Recruiting at 55 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

174 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing botensilimab alone and with balstilimab in adults with advanced skin cancer who haven't responded to other treatments. The drugs aim to help the immune system better recognize and attack cancer cells. The study will see if these treatments are safe and effective.

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.

What safety information is available for Botensilimab and related treatments?

Botensilimab and similar treatments, like other immune checkpoint inhibitors, can cause skin-related side effects. These may include rashes, acne-like eruptions, and more serious conditions like Stevens-Johnson syndrome (a severe skin reaction). While most side effects are mild, some can be serious, so it's important to monitor for any skin changes during treatment. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Agenus Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical profile of cutaneous adverse events of immune checkpoint inhibitors in a single tertiary center. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cutaneous Adverse Events of Systemic Melanoma Treatments: A Retrospective Single-Center Analysis. [2023]

3. United States 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. [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Dermatologic adverse events of the new targeted anticancer therapies used in oncodermatology]. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Selected cutaneous adverse events in patients treated with ICI monotherapy and combination therapy: a retrospective pharmacovigilance study and meta-analysis. [2023]