Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Running, not enrolling · Phase 2

Conditions studied: Anaplastic Large Cell Lymphoma, ALK-Negative, Anaplastic Large Cell Lymphoma, ALK-Positive, Apocrine Carcinoma, Carcinoma Arising From Cylindroma, Carcinoma Arising From Spiradenoma, Digital Papillary Adenocarcinoma, Endocrine Mucin-Producing Sweat Gland Carcinoma, Extramammary Paget Disease, Extraocular Sebaceous Carcinoma, Hidradenocarcinoma, Malignant Sweat Gland Neoplasm, Merkel Cell Carcinoma, Microcystic Adnexal Carcinoma, NK-Cell Lymphoma, Unclassifiable, Papillary Adenocarcinoma, Porocarcinoma, Primary Cutaneous Mucinous Carcinoma, Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Recurrent T-Cell Non-Hodgkin Lymphoma, Refractory Anaplastic Large Cell Lymphoma, Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Refractory Merkel Cell Carcinoma, Refractory Mycosis Fungoides, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Refractory Skin Squamous Cell Carcinoma, Refractory T-Cell Non-Hodgkin Lymphoma, Sezary Syndrome, Signet Ring Cell Adenocarcinoma, Skin Adenoid Cystic Carcinoma, Skin Adnexal Carcinoma, Skin Basal Cell Carcinoma, Skin Basosquamous Cell Carcinoma, Skin Keratoacanthoma, Skin Squamous Cell Carcinoma, Squamoid Eccrine Ductal Carcinoma, Squamous Cell Carcinoma of Unknown Primary, Sweat Gland Carcinoma, Trichilemmal Carcinoma, Vulvar Squamous Cell Carcinoma

In brief

This phase II trial studies how well talimogene laherparepvec and nivolumab work in treating patients with lymphomas that do not responded to treatment (refractory) or non-melanoma skin cancers that have spread to other places in the body (advanced) or do not responded to treatment. 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 nivolumab, 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 nivolumab may work better compared to usual treatments in treating patients with lymphomas or non-melanoma skin cancers.

Key facts

Study ID

NCT02978625

Run by

National Cancer Institute (NCI)

People needed

68

Starts

2017-09-27

Expected to finish

2027-09-01

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologic or cytologic diagnosis of non-melanoma skin cancer (NMSC) or lymphomas other than B-cell lymphomas; as both of those terms are categories rather than specific diagnoses, specific guidance on eligible tumor types is provided below
• PART I (before February 2020 amendment): Included tumor types
• T cell and NK cell lymphomas, including, but not limited to: cutaneous T-cell lymphomas (CTCL), mycosis fungoides (MF), Sezary syndrome (SS), peripheral T-cell lymphoma (PTCL), ALK-positive and ALK-negative anaplastic large cell lymphoma (ALCL), and NK-cell lymphomas
• Merkel cell carcinoma
• Squamous cell carcinoma of the skin, including keratoacanthomas, vulvar squamous carcinoma, and mixed histology tumors, such as basosquamous carcinoma, and squamous cell carcinoma of unknown primary consistent with skin origin
• Other non-melanoma skin cancers
• Basal cell carcinoma
• Malignant sweat gland tumors, including porocarcinoma, hidradenocarcinoma, spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and related entities, squamoid eccrine ductal carcinoma, cutaneous adenoid cystic carcinoma, digital papillary adenocarcinoma, primary cutaneous mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma, primary cutaneous signet ring cell carcinoma, cutaneous apocrine gland carcinoma, and extraocular sebaceous carcinoma
• Adnexal carcinoma
• Trichilemmal carcinoma
• Extramammary Paget's disease
• Any other rare tumor of the skin with approval of principle investigator (PI)
• PART II (after February 2020 amendment):
• The Merkel cell carcinoma (MCC)-2 cohort will include patients with MCC
• The squamous cell carcinoma (SCC)-2 cohort will include patients with SCC
• PART I (before February 2020 amendment): Patients with T cell and natural killer (NK) cell lymphomas must be refractory to, be intolerant of, have relapsed following, or have refused all standard life-prolonging therapies
• PART I (before February 2020 amendment): Patients with non-melanoma skin cancers (NMSC) must have advanced or refractory tumors
• Advanced/unresectable is defined by at least 1 of the following criteria: tumors 2 cm or more, tumors considered unresectable, tumors invading deep tissues such as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes and/or distant sites
• Refractory is defined by persistent or recurrent tumor despite prior therapy consisting of at least 1 of the following: surgery, radiation therapy, intralesional therapy, topical therapy, or systemic therapy
• PART I (before February 2020 amendment): Subjects must have at least 1 cutaneous, subcutaneous, or nodal lesion that is suitable for intralesional injection, with or without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc) are not eligible for injection because the area cannot be properly contained with an occlusive dressing
• PART I (before February 2020 amendment): Subjects must have radiographically or clinically measurable disease, defined as at least one lesion that is >= 10 mm in diameter in at least 1 dimension, or an aggregate of lesions that measures >= 10 mm in diameter in at least 1 dimension
• PART I (before February 2020 amendment): Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions
• PART I (before February 2020 amendment): Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• PART I (before February 2020 amendment): Absolute neutrophil count (ANC) >= 1.2 x 10\^9/L
• PART I (before February 2020 amendment): Hemoglobin >= 9 g/dL without transfusion in the preceding 7 days

You may not qualify if…

• Excluded tumor types
• Melanoma
• Bone sarcomas
• Soft tissue sarcomas, including angiosarcoma, primary cutaneous leiomyosarcoma, dermatofibrosarcoma protuberans
• Leukemias
• Myeloid sarcoma, leukemia cutis, and chloroma
• Hodgkin's lymphoma
• B cell lymphoma
• Patients who have had systemic therapy or radiotherapy within 3 weeks prior to the first dose of study therapy
• Untreated central nervous system (CNS) involvement; patients with known brain metastases are eligible if they have been treated and are stable in the view of the treating investigator
• Previous treatment with talimogene laherparepvec or other herpes virus based therapy; (prior therapy with checkpoint inhibitors and/or other immunotherapy is allowed)
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1 excepting alopecia, peripheral sensory neuropathy, and stable endocrine insufficiencies such as thyroid and adrenal insufficiency)
• Second primary malignancy, only if it would affect the safety of the treatment or the subject's ability to complete study-related procedures
• History or evidence of active autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other); or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) within 2 months of enrollment; (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)
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as severe combined immunodeficiency disease
• Receiving systemic immunosuppressive therapy including prednisone > 10 mg per day (or equivalent), tacrolimus, everolimus, sirolimus, mycophenolate mofetil, etanercept, infliximab, etc.
• Recipients of solid organ, bone marrow, or stem cell transplants; auto transplant recipients are allowed
• Notes: Oral steroid doses =< 10 mg/day of prednisone (or equivalent) are not considered immunosuppressive and are permitted; inhaled and intraarticular corticosteroids are permitted
• Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
• Viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use
• Other viral infections:
• Known to have acute or chronic active hepatitis B or hepatitis C infection
• Known to have human immunodeficiency virus (HIV) infection
• Prior therapy with viral-based tumor vaccine

Where it is running

• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Keck Medical Center of USC Pasadena — Pasadena, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States
• UM Sylvester Comprehensive Cancer Center at Aventura — Aventura, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Kendall — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States
• Northwestern University — Chicago, Illinois, United States
• University of Kansas Clinical Research Center — Fairway, Kansas, United States
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States
• University of Kansas Hospital-Indian Creek Campus — Overland Park, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
• Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
• University of Kansas Cancer Center - North — Kansas City, Missouri, United States
• University of Kansas Cancer Center - Lee's Summit — Lee's Summit, Missouri, United States
• University of Kansas Cancer Center at North Kansas City Hospital — North Kansas City, Missouri, United States

Full record on ClinicalTrials.gov

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