PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma

NCT02557321 | Unknown Phase 1

• 1 other identifier: PV-10-MM-1201
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

This is an international multicenter, open-label, sequential phase study of intralesional (IL) PV-10 in combination with immune checkpoint inhibition. Metastatic melanoma patients (Stage IV or Stage III unresectable, in-transit or satellite disease) with at least one injectable lesion who are candidates for pembrolizumab (both treatment naïve patients and treatment refractory patients who have failed to achieve a complete or partial response to or previously progressed on one or more checkpoint inhibitor) will be eligible for study participation. In the Phase 1b portion of the study, all participants will receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone (i.e., PV-10 + standard of care vs. standard of care).

Conditions

Melanoma

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of the combination regimen assessed by adverse events (AEs)

  Phase 1b: Safety and tolerability of the combination regimen will be assessed by monitoring the frequency, duration, severity and attribution of adverse events (AEs) and toxicities requiring discontinuation of study treatment, and evaluating changes in laboratory values and vital signs

  Start of treatment until 4 weeks after final administration of PV-10

• Progression Free Survival (PFS)

  Phase 2: Response evaluated by blinded independent review committee assessment per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

  Up to 24 months from initiation of study treatment

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  Up to 24 months from initiation of study treatment

• Objective Response Rate (ORR)

  Up to 24 months from initiation of study treatment

• Change in immune biomarkers

  Up to 28 weeks from initiation of study treatment

• Overall Survival (OS)

  24 months from initiation of study treatment for last subject randomized

• Safety and tolerability of the combination regimen assessed by adverse events (AEs)

  Start of treatment until 4 weeks after final administration of PV-10

Study Arms (3)

Phase 1b

EXPERIMENTAL

PV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks)

Drug: PV-10; Drug: Pembrolizumab

Phase 2 (Arm 1)

EXPERIMENTAL

PV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks)

Drug: PV-10; Drug: Pembrolizumab

Phase 2 (Arm 2)

ACTIVE COMPARATOR

Pembrolizumab (2 mg/kg every 3 weeks)

Drug: Pembrolizumab

Interventions

PV-10 DRUG

PV-10 will be administered by intralesional injection every 3 weeks at Day 1 (Week 1), Week 4, Week 7, Week 10 and Week 13

Also known as: Rose Bengal Disodium

Phase 1b; Phase 2 (Arm 1)

Pembrolizumab DRUG

Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1)

Phase 1b; Phase 2 (Arm 1); Phase 2 (Arm 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older, male or female.
• Histologically or cytologically confirmed diagnosis of melanoma.
• Stage IV or Stage III (unresectable, in-transit or satellite) melanoma.
• At least 1 Injectable Lesion (i.e., cutaneous, subcutaneous, soft tissue, superficial nodal or palpable nodal lesion with longest diameter at least 5 mm that is suitable for injection with PV-10).
• A minimum of 1 measurable Target Lesion that can be accurately measured by calipers, computed tomography (CT) or magnetic resonance imaging (MRI) consisting of at least one of the following:
• at least one cutaneous lesion (each lesion ≥ 10 mm longest diameteror up to 5 lesions in aggregate having a sum of longest diameters ≥ 10 mm); and/or
• at least one subcutaneous or soft tissue lesion (each lesion ≥ 10 mm in longest diameter by CT or MRI); and/or
• at least one nodal lesion (each lesion ≥ 15 mm in short axis diameter by CT or MRI); and/or
• at least one visceral lesion (each lesion ≥ 10 mm in longest diameter by CT or MRI).
• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.
• Clinical Laboratories:
• absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥100 x 109/L
• estimated creatinine clearance (CrCl, by Cockcroft-Gault formula) or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2
• total bilirubin ≤ 3 times the upper limit of normal (ULN)
• aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) ≤ 5 times the upper limit of normal (ULN)

You may not qualify if:

• Untreated or clinically active melanoma brain metastases.
• Subjects with ≤ 3 brain metastases and each ≤ 1 cm size that were treated with either surgical resection and/or radiation therapy are eligible for study participation provided (a) there is no evidence of progressive central nervous system (CNS) disease on brain imaging at least 30 days after definitive treatment and (b) the subject is not taking prednisone at \>10 mg or equivalent daily.
• Subjects with \> 1 cm or \> 3 in number treated brain metastases are eligible for study participation provided (a) there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy and (b) if the subject is not taking prednisone at \>10 mg or equivalent daily.
• Prior treatment with PV-10 or any checkpoint inhibitor; however, subjects (a) who have failed to achieve a complete or partial response within 24 weeks following initiation of checkpoint inhibition or (b) who progressed after more than 12 weeks of checkpoint inhibition are eligible for study participation in the Phase 1b Expansion Cohort 1 without washout period for checkpoint inhibition.
• Other prior cancer therapy or anti-cancer vaccine within the lesser of 4 weeks or 5 half-lives before initial study treatment.
• Known sensitivity to any of the products or components to be administered during dosing.
• Concurrent or Intercurrent Illness:
• History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other systemic autoimmune disease.
• Evidence of clinically significant immunosuppression.
• Impaired wound healing or other extremity complications due to severe or uncontrolled diabetes mellitus in subjects whose Injectable Lesions are located in an extremity.
• Severe peripheral vascular disease (i.e., severe claudication \[pain occurring after less than 200 meters of walking\], rest pain, ischemic ulceration or gangrene) in subjects whose Injectable Lesions are located in an extremity.
• Significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise the subject's safety or compliance or interfere with interpretation of study results.
• Uncontrolled thyroid disease or cystic fibrosis.
• Clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders.
• Malignancy other than melanoma within 2 years of enrollment except for: adequately treated (i.e., with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer.

Sponsors & Collaborators

• Provectus Biopharmaceuticals, Inc.: lead

Study Sites (5)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

St Luke's University Health Network

Easton, Pennsylvania, 18045, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77230, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Rose Bengal B; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Eric Wachter, Ph.D.

  Provectus Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2015
• First Posted: September 23, 2015
• Study Start: October 1, 2015
• Primary Completion: May 1, 2023
• Study Completion: April 1, 2025
• Last Updated: November 21, 2023

Record last verified: 2023-11

Locations

US (5)