Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

NCT02965716 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2016-01698S1607U10CA180888
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 20

Brief Summary

This phase II trial studies how well talimogene laherparepvec and pembrolizumab work in treating patients with stage III-IV melanoma. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and pembrolizumab may work better in treating patients with melanoma by shrinking the tumor.

Conditions

Advanced Melanoma; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Unresectable Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Number of participants with a complete response, defined as the disappearance of all target and non-target lesions, or partial response, defined as a greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable legions. ORR is measured using RECIST 1.1 guidelines.

  Up to 5 years post registration or until death

Secondary Outcomes (7)

• Durable Response Rate

  Up to 5 years post registration or until death

• Objective Response Rate (ORR) in Injected Lesions

  Up to 5 years post registration or until death

• Objective Response Rate (ORR) in Non-Visceral, Non-Injected Lesions

  Up to 5 years post registration or until death

• Objective Response Rate (ORR) in Visceral Lesions (Cohort A)

  Up to 5 years post registration or until death

• Progression-Free Survival (PFS)

  Up to 5 years post registration or until death

Study Arms (1)

Treatment (talimogene laherparepvec, pembrolizumab)

EXPERIMENTAL

Patients receive talimogene laherparepvec IL and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Biological: Talimogene Laherparepvec

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Treatment (talimogene laherparepvec, pembrolizumab)

Talimogene Laherparepvec BIOLOGICAL

Given IL

Also known as: ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VEC

Treatment (talimogene laherparepvec, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically confirmed stage IV or unresectable stage III melanoma; patients must not have disease that is suitable for local therapy, administered with curative intent
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; contrast-enhanced computed tomography (CT) scans of the chest, abdomen and pelvis are required; a whole body positron emission tomography (PET)/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the chest, abdomen and pelvis; imaging of the head and neck, or the limbs is required only if the patient has a lesion(s) in these areas; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; if skin lesions are being followed as measurable disease, photograph with a ruler included and physician's measurements, must be kept in the patients chart as source documentation; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration.; all disease must be assessed and documented on the baseline tumor assessment form (RECIST 1.1)
• Cohort A: Patients must have at least one measurable visceral lesion (per RECIST 1.1); a visceral lesion is any solid organ except for skin, lymph node, and musculoskeletal tissue; at least one of these visceral lesions must be measurable per RECIST 1.1
• Patients must, in the opinion of the treating physician, be candidates for intralesional administration into cutaneous, subcutaneous, or nodal lesions
• Patients may have brain metastases if all lesions have been treated with stereotactic radiation therapy, craniotomy, or gamma knife therapy and have not required steroids for at least 14 days prior to registration
• Patient must have had prior treatment with anti-PD-1 or anti-PD-L1 agents and have documented disease progression on these agents prior to registration; patients who have progressed after adjuvant anti-PD1/L1 agents are eligible
• Patients must be \>= 18 years of age
• Patients must have Zubrod performance status =\< 2
• Absolute neutrophil count (ANC) \>= 1,500/mcL (within 28 days prior to registration)
• Hemoglobin \>= 8 g/dL (within 28 days prior to registration)
• Platelets \>= 100,000/mcL (within 28 days prior to registration)
• Albumin \>= 2.5 g/dL (within 28 days prior to registration)
• Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) except patients with documented Gilbert's syndrome (=\< 3 x IULN is eligible) (within 28 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =\< 3 x IULN (within 28 days prior to registration)
• Patients must have lactate dehydrogenase (LDH) obtained prior to registration

You may not qualify if:

• Cohort B: Patients must not have any visceral lesions
• Patients must not have had surgery, biologic therapy, or hormonal therapy within 14 days prior to registration; patients must not have had chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to registration; patients must not have had a monoclonal antibody for cancer treatment, except anti-PD1/L1 antibodies, within 28 days prior to registration
• Patients must have recovered from all adverse events due to prior anti-cancer therapy (residual toxicity =\< grade 1) prior to registration, with the exception of patients with =\< grade 2 neuropathy, =\< grade 2 hypothyroidism, or =\< grade 2 alopecia
• If patients received major surgery, they must have recovered adequately from toxicity and/or complications from the intervention prior to registration
• Patients must not have received prior treatment with talimogene laherparepvec (T-VEC); prior treatment with T-VEC is defined as receiving at least one injection with 1 x 10\^8 plaque forming units (pfu)
• Patients must not have received any live vaccine within 30 days prior to registration; seasonal flu vaccines that do not contain live virus are permitted
• Patients must not be planning to receive other biologic therapy, radiation therapy, hormonal therapy, chemotherapy, surgery, or other therapy while on this protocol; palliative radiation therapy or surgery can be considered for symptomatic non-target lesions after discussions with the study team
• Patients must not require use of systemic corticosteroid within 14 days prior to registration or during protocol treatment; patients with preexisting severe autoimmune disease requiring systemic corticosteroids or ongoing immunosuppression are not eligible
• Patients must not have known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) due to contraindication of talimogene laherparepvec (T-VEC) in immune-compromised patients and that administration of talimogene laherparepvec (T-VEC) has not been tested in HIV-positive patients; the use of physiologic doses of corticosteroids may be approved after consultation with the study chair
• Patients must not have history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Patients must not have an active infection requiring systemic therapy nor a viral infection requiring intermittent treatment with an antiherpetic drug, other than intermittent topical use
• Patients must not have active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) which requires intermittent or chronic treatment with an anti-herpetic drug other than intermittent topical use
• Patients must not have organ allografts
• Patients must not have an uncontrolled intercurrent illness or whose control may be jeopardized by the treatment with the study therapy, or psychiatric illness/social situations which would limit compliance with study requirements
• Patients must not have active autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other) that requires systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in the past 2 years; replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36688, United States

Location

CTCA at Western Regional Medical Center

Goodyear, Arizona, 85338, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan, 48183, United States

Location

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, 48038, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Allegiance Health

Jackson, Michigan, 49201, United States

Location

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

Location

Kansas City Veterans Affairs Medical Center

Kansas City, Missouri, 64128, United States

Location

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; talimogene laherparepvec

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

Results Point of Contact

• Title: Melanoma Committee Statistician
• Organization: SWOG Data Management Center

jmoon@fredhutch.org

206-667-4623

Study Officials

• Siwen Hu-Lieskovan

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: November 17, 2016
• Study Start: June 5, 2018
• Primary Completion: June 30, 2023
• Study Completion (Estimated): November 4, 2026
• Last Updated: November 18, 2025
• Results First Posted: August 27, 2024

Record last verified: 2025-11

Locations

US (20)