Advanced Melanoma
Conditions
Keywords
Open-label, Monotherapy, Combination Therapy, Anti-PD-1, Anti-PD-L1, Anti-CTLA-4, Immunotherapy
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.
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.
Interventions
DRUGBotensilimab
An anti-CTLA-4 monoclonal antibody
DRUGBalstilimab
An anti-PD-1 monoclonal antibody
Sponsors
Agenus Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To participate in the study, participants must meet all the following inclusion criteria: Cohort A only: 1. 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. 2. 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. 3. 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: 1. 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. 2. Progression on most recent anti-cancer therapy. 3. 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: 1. Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures. 2. Histologically confirmed Stage III (unresectable) or Stage IV histologically confirmed cutaneous melanoma as per the American Joint Committee on Cancer 8th edition staging system. 3. Measurable disease on baseline imaging per RECIST 1.1 criteria. 4. BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the screening period. 5. Life expectancy ≥ 3 months. 6. Eastern Cooperative Oncology Group performance status of 0 or 1. 7. Adequate organ function is defined as the following laboratory values within 14 days of Cycle 1 Day 1 (C1D1): 1. Neutrophils \> 1500/microliter (μL) (stable off any growth factor within 4 weeks of first study treatment administration). 2. Platelets \> 100 × 10\^3/μL (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration). 3. Hemoglobin \> 8.0 grams/deciliter (g/dL) (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration). 4. Creatinine clearance ≥ 45 milliliters/minute (measured or calculated using modification of diet in renal disease). 5. Aspartate aminotransferase/alanine aminotransferase \< 3.0 × upper limit of normal (ULN). 6. Total bilirubin \< 1.5 × ULN, or \< 3.0 × ULN for participants with Gilbert syndrome. 7. Albumin ≥ 3.0 g/dL. 8. International normalized ratio or prothrombin time ≤ 1.5 × ULN and activated partial thromboplastin time ≤ 1.5 × ULN (unless participant is receiving anticoagulant therapy). 8. 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. 9. 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. 10. 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.
Exclusion criteria
To participate in the study, participants must meet none of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | First dose through up to 3 months | Objective response rate will be determined using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Progression-free survival will be determined using RECIST 1.1. |
| 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) | Duration of response will be determined using RECIST 1.1. |
| Overall Survival Time | First dose through up to 3 months | Overall survival will be quantified as a median. |
| Frequency of Treatment-emergent Adverse Events | First dose through up to 3 months | — |
Countries
Belgium, Brazil, France, Germany, Italy, Russia, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Agenus Inc.
Outcome results
None listed