A Phase II Multicenter, Open-label Study to Evaluate the Safety and Efficacy of the CD40 Agonistic Antibody Sotigalimab (APX005M) With or Without Stereotactic Body Radiation Therapy in Adults With Unresectable or Metastatic Melanoma
Overview
- Phase
- Phase 2
- Intervention
- sotigalimab
- Conditions
- Unresectable Melanoma
- Sponsor
- Apexigen America, Inc.
- Enrollment
- 45
- Locations
- 19
- Primary Endpoint
- Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Overall Response Rate (ORR)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multicenter, open label, Phase 2 study, with 3 parallel cohorts. The aim of the study is to evaluate the efficacy of sotigalimab (APX005M) administered at 2 different schedules to adult participants with unresectable or metastatic melanoma. Participants who have not received prior immunotherapy will be alternately assigned to 1 of 2 cohorts with different sotigalimab administration schedules as long as both are open for enrollment. Participants who have failed any number of prior lines of therapy will be assigned to a 3rd cohort of sotigalimab in combination with radiation therapy.
Detailed Description
This is a multicenter, open label, Phase 2 study, with 3 parallel cohorts. The aim of the study is to evaluate the efficacy of Sotigalimab administered at 2 different schedules to adult participants with unresectable or metastatic melanoma who have not received prior immunotherapy. Enrolled participants will be alternately assigned to one of the following 2 cohorts (groups) as long as both cohorts are open. Cohort 1: APX005M administered IV at 0.3 mg/kg every 3 weeks (21-day cycle) Cohort 2: APX005M administered IV at 0.3 mg/kg every 2 weeks (14-day cycle) Sotigalimab in combination with stereotactic body radiation therapy (SBRT) in adults with unresectable or metastatic melanoma who have failed any number of prior lines of therapy will be assigned to Cohort 3: Sotigalimab administered IV at 0.3 mg/kg in combination with radiation therapy every 2 weeks (14 day cycle) up to 16 weeks followed by sotigalimab administered IV at 0.3 mg/kg every 2 weeks (14-day cycle). Primary Objective • Evaluate the overall response rate (ORR) by RECIST 1.1 measurements in each of the cohorts. Secondary Objectives * Evaluate the safety of sotigalimab alone or in combination with radiation therapy in each cohort * Evaluate ORR by modified RECIST 1.1 for immune-based therapeutics (iRECIST) in each cohort * Evaluate median duration of response (DOR) in each cohort
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed unresectable or metastatic melanoma
- •Subjects with BRAF activating mutation must have received a BRAF inhibitor and/or MEK inhibitor regimen prior to study entry
- •Signed written informed consent approved by the relevant local ethics committee(s)
- •Male or female ≥18 years old at time of consent
- •Measurable disease by RECIST 1.1
- •a. For Cohort 3 only, subjects must have at least 3 measurable target lesions
- •ECOG performance status of 0 or 1
- •Resolution of all disease or prior treatment-related toxicities to Grade ≤1, with the exception of alopecia, Grade 2 neuropathy and laboratory abnormalities (parameters below apply). If subject received major surgery or radiation therapy of \>30 Gy, they must have recovered from the toxicity and/or complications from the intervention
- •Adequate organ function within 14 days prior to first dose of investigational therapy(ies):
- •WBC ≥2 x 109/L in absence of growth factor support
Exclusion Criteria
- •Prior Therapy:
- •Cohorts 1 and 2 only: Previous exposure to any immunomodulatory agent (such as CTLA-4, PD-1/PD-L1, IDO inhibitors, interferon, CD40 agonist etc.).
- •Cohort 3 only: Prior therapy with a CD40 agonist. Any number of prior lines of therapy are eligible. A minimum washout period of 21 days from last line of therapy until investigational therapy(ies) administration should be observed.
- •Second malignancy (solid or hematologic) within the past 3 years except locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
- •Active, known, clinically serious infections (≥ Grade 2 according to NCI-CTCAE v4.03) within the 14 days prior to first dose of investigational therapy(ies)
- •Use of systemic corticosteroids or other systemic immunosuppressive drugs within 28 days prior to first dose of investigational therapy(ies) (except inhaled corticosteroids)
- •a. The use of physiologic doses of corticosteroids may be approved /w consultation Medical Monitor (or designee)
- •Major surgery within 4 weeks prior to first dose of sotigalimab
- •Concurrent treatment with any anticancer agent and palliative radiation, unless approved by MM (or designee)
- •History of allogeneic bone marrow transplantation
Arms & Interventions
Cohort 1
Sotigalimab administered IV at 0.3 mg/kg every 3 weeks (21 day) treatment cycles
Intervention: sotigalimab
Cohort 2
Sotigalimab administered IV at 0.3 mg/kg every 2 weeks (14 day) treatment cycles
Intervention: sotigalimab
Cohort 3
Metastatic melanoma participants who have failed any number of prior lines of therapy with minimum 3 measurable lesions. Sotigalimab administered IV at 0.3mg/kg in combination with Stereotactic Body Radiation Therapy (SBRT) every 2 weeks (14-day) treatment cycles up to 16 weeks followed by sotigalimab administered IV at 0.3 mg/kg every 2 weeks (14-day) treatment cycles.
Intervention: sotigalimab
Outcomes
Primary Outcomes
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Overall Response Rate (ORR)
Time Frame: 12 months
The percentage of participants having reached a confirmed Complete Response (CR) or Partial Response (PR) by RECIST 1.1, relative to the number of participants belonging to the Efficacy Population. Confidence Intervals (CIs) were calculated using exact (Clopper-Pearson) method. CR: Disappearance of all target lesions and nontarget (NT) lesions; PR: \>30% decrease in the sum of the longest diameter of target lesions and no progressive disease in NT lesions or new lesions.
Secondary Outcomes
- RECIST 1.1 Duration of Response (DoR)(12 months)
- Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST 1.1) Overall Response Rate (iORR)(12 months)