Open-label, Multi-center Phase IIa Study to Evaluate the Efficacy, Safety, and Immunological Response of OBP-301, Telomerase Specific Replication-competent Oncolytic Adenovirus in Patients With Unresectable Metastatic Melanoma
Overview
- Phase
- Phase 2
- Intervention
- OBP-301
- Conditions
- Melanoma Stage III
- Sponsor
- Syneos Health
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Evaluate objective response rate [ORR]) to OBP-301 in both injected and noninjected lesions
- Last Updated
- 7 years ago
Overview
Brief Summary
Open-label, single-arm, multi-center, Phase IIa study to evaluate the efficacy, safety, and immunological response of OBP 301 in patients with unresectable/unresected metastatic melanoma. This proof of concept study will be undertaken in male and female patients with unresectable Stage III and IV melanoma. Patients with unresectable/unresected mucosal melanoma may be enrolled after consultation with the Medical Monitor.
Detailed Description
Primary Objective: The primary objective of this study is to evaluate the overall tumor sites response (objective response rate \[ORR\]) to OBP-301 in both injected and noninjected lesions up to and including Week 24 in patients with unresectable/unresected Stage III and IV melanoma. The ORR is defined as the rate of complete response (CR) and partial response (PR) based on the modified immune-related response criteria (irRC) 1.0. The modification is to allow the identification of up to 10 cutaneous, subcutaneous, and/or lymph node tumor lesions and identify the lesions as target and nontarget lesions. Secondary Objectives: * To evaluate the ORR up to and including Week 24 in injected target lesions based on the modified irRC 1.0 and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * To evaluate the ORR up to and including Week 24 in noninjected target lesions based on modified irRC 1.0 and RECIST 1.1 * To evaluate the ORR in both injected and noninjected target lesions at Week 12 based on the modified irRC 1.0 and RECIST 1.1 * To evaluate duration of response and time to response * To evaluate progression free survival (PFS) at Week 24 and Week 48 * To evaluate overall survival (OS) at Week 24 and Week 48 * To evaluate the safety of OBP 301 Exploratory Objective (optional): The optional exploratory objective of this study is to investigate the tumor immunological response in blood and tumor tissue following treatment with OBP-301.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed malignant melanoma at Screening that is unresectable/unresected Stage IIIB, IIIC, IIID or IV. Patients with unresectable mucosal melanoma may be enrolled after consultation with the Medical Monitor.
- •Patients must have received and failed or refused available therapy for unresectable/unresected Stage III or IV melanoma.
- •Patients must be ≥ 18 years of age.
- •At least 2 cutaneous, subcutaneous and/or lymph node target lesions that are greater or equal to 1 cm in the longest diameter. One of the cutaneous, subcutaneous and/or lymph node target lesions should be designated at Screening as a noninjected target lesion. Willing to have biopsy specimens taken at Screening and at Week
- •Life expectancy of ≥ 6 months from the first OBP-301 treatment.
- •Karnofsky Performance Status Scale (KPS) score of ≥
- •Adequate organ function, hematologic status, coagulation status, kidney function, and liver function as follows:
- •Absolute neutrophils \> 1,500/µL
- •Hemoglobin \> 9 g/dL, without transfusion or hematopoietic growth factor
- •Platelets \> 100,000/µL. Patients with ≤ 100,000 platelet count may be allowed into the study on a case-by-case basis after consultation with the Medical Monitor.
Exclusion Criteria
- •Patients who have had administration of chemotherapy, target therapy, and/or immunotherapy within the last 4 weeks before the first OBP-301 administration.
- •Patients who have received other investigational medication within the last 4 weeks or a period of its 5 half-lives (whichever is shorter) before the first OBP-301 administration.
- •Patients who have had radiotherapy within the last 4 weeks before the first OBP-301 administration.
- •Effects of any other prior therapies not reverted to ≤ Grade 1 (or ≤ Grade 2 for alopecia and peripheral neuropathy).
- •Patients who have any liver metastases or visceral metastasis of ≥ 3 cm, plus evidence of progression meeting irRC 1.0 within 1 month before the first OBP-301 administration.
- •Patients with clinically active brain metastases. However, patients with previously currently stable brain metastases on medication (i.e., steroids and/or anti-seizure medications) may be enrolled after consultation with the Medical Monitor.
- •Patients known to have acute or chronic active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
- •Patients diagnosed with additional malignancy within 3 years before the first OBP-301 administration with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers.
- •Patients requiring chronic systemic immunosuppressive medication including pharmacologic dose of glucocorticoids or cyclosporine should be evaluated by the Medical Monitor for enrollment eligibility.
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/psychological incompetence, whereby in the opinion of the Investigator the patient is assessed as being unable to provide information, consent, or comply with the study requirements and procedures.
Arms & Interventions
OBP-301
Eligible patients with unresectable Stage III and IV melanoma will receive up to 13 treatments of OBP 301 at a concentration of 1 × 1012 virus particles (VP)/mL for 24 weeks.
Intervention: OBP-301
Outcomes
Primary Outcomes
Evaluate objective response rate [ORR]) to OBP-301 in both injected and noninjected lesions
Time Frame: up to Week 24
Objective response rate \[ORR\]) to OBP-301 in both injected and noninjected lesions in patients with unresectable/unresected Stage III and IV melanoma. The modification is to allow the identification of up to 10 cutaneous, subcutaneous, and/or lymph node tumor lesions and identify the lesions as target and nontarget lesions.
Secondary Outcomes
- Overall Response Rate at weeks 6, 12, 18, and 24 in the combined and individual injected lesions(Week 24 and Week 48)
- Best Overall Response Rate at weeks 6, 12, 18, and 24 in injected and noninjected lesions(Week 24 and Week 48)
- Time to Treatment Response from start date to end date(Week 24 and Week 48)
- Duration of response of injected and noninjected lesions(Week 24 and Week 48)
- Safety of OBP-301 as assessed by changes in clinical laboratory parameters(Through study completion)
- Overall Survival at weeks 24 and 48(Week 24 and Week 48)
- Safety of OBP-301 as assessed by incidence of AEs and SAEs(Through study completion)
- Progression Free Survival at weeks 24 and 48(Week 24 and Week 48)