Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
A Phase II Study of Talimogene Laherparepvec Followed by Talimogene Laherparepvec + Nivolumab in Refractory T Cell and NK Cell Lymphomas, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Other Rare Skin Tumors
5 other identifiers
interventional
68
1 country
36
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2017
Longer than P75 for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 30, 2016
CompletedFirst Posted
Study publicly available on registry
December 1, 2016
CompletedStudy Start
First participant enrolled
September 27, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
April 13, 2026
February 1, 2026
9.9 years
November 30, 2016
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Response rate to talimogene laherparepvec alone (Part I)
Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Up to 1 year
Best overall response rate to talimogene laherparepvec and nivolumab combination therapy (Part II)
Will be assessed by RECIST version 1.1.
Up to 1 year
Secondary Outcomes (10)
Durable response rate
Up to 1 year
Response rate by cancer type
Up to 1 year
Response rate of injected lesions
Up to 1 year
Response rate of non-injected lesions
Up to 1 year
Frequency of curative surgery (unresectable lesion becomes resectable)
Up to 1 year
- +5 more secondary outcomes
Other Outcomes (4)
Change in herpes simplex virus (HSV) serostatus assessed in blood specimens
Baseline to week 6
Biomarker analysis of %PD-L1, flow cytometry for HVEM, NECTIN1/2, and IDO, tryptophan and L-kynurenine, cytokine levels, Nanostring, number of non-synonymous mutations, and % T-cell receptor (TCR) clonality
Up to 1 year
Biomarker analysis of necrosis and Nanostring
Up to 1 year
- +1 more other outcomes
Study Arms (1)
Treatment (talimogene laherparepvec, nivolumab)
EXPERIMENTALPatients receive talimogene laherparepvec IT and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo, CT scan or PET/CT on study. Patients also undergo blood sample collection and biopsies on study.
Interventions
Undergo tissue biopsy
Undergo CT
Given IV
Given IT
Undergo blood sample collection
Correlative studies
Eligibility Criteria
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
- +32 more criteria
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:
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Keck Medical Center of USC Pasadena
Pasadena, California, 91105, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ann (Annie) W Silk
Dana-Farber - Harvard Cancer Center LAO
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 30, 2016
First Posted
December 1, 2016
Study Start
September 27, 2017
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
September 1, 2027
Last Updated
April 13, 2026
Record last verified: 2026-02