Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin

NCT ID: NCT04163952

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-31
• Study Completion Date: 2025-03-28

Brief Summary

This phase I trial studies the side effects and how well talimogene laherparepvec and panitumumab work in treating patients with squamous cell carcinoma of the skin that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Talimogene laherparepvec is a type of vaccine made from a gene-modified virus that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as panitumumab, 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 panitumumab may work better in treating patients with squamous cell carcinoma of the skin compared to panitumumab alone.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety of the combined treatment of talimogene laherparepvec and panitumumab.

II. To determine the preliminary efficacy of the combined treatment of talimogene laherparepvec and panitumumab, in comparison to single-agent panitumumab by historical control.

SECONDARY OBJECTIVES:

I. To assess the clinical efficacy of panitumumab in combination with intratumoral talimogene laherparepvec in terms of immune-related progression-free survival (irPFS) at 12 months, progression-free survival (PFS) hazard ratio, overall response rate (ORR), 1-year survival, overall survival (OS) and time to resectability.

II. To measure the pathologic complete response rate to panitumumab combined with talimogene laherparepvec.

III. Assess the response of injected and non-injected tumor deposits after panitumumab and talimogene laherparepvec.

IV. Assess the time to initial response. V. Assess the durable response rate.

VI. To analyze the following molecular correlates with response to therapy to confirm mechanism of action, and identify potential future targeted strategies and biomarkers of response:

VIa. Mutation load in tumor tissue by next generation sequencing. VIb. Deoxyribonucleic acid (DNA) mutation signature in tumor tissue pre- and post-therapy by next generation sequencing.

VIc. Messenger ribonucleic acid (mRNA) signature in tumor tissue pre-and post-therapy by Nanostring technology.

VId. Immune cell populations and immune profile in pre- and post-therapy tumor tissue and peripheral blood by flow cytometry and immunohistochemistry (IHC).

OUTLINE:

Patients receive talimogene laherparepvec intratumorally (IM) on day 1. Patients then receive talimogene laherparepvec IM and panitumumab intravenously (IV) over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.

After completion of study treatment, patients are followed up at 30 days and then every 2 months for 2 years.

Conditions

Locally Advanced Skin Squamous Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Recurrent Skin Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (talimogene laherparepvec, panitumumab)

Patients receive talimogene laherparepvec IM on day 1. Patients then receive talimogene laherparepvec IM and panitumumab IV over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: BIOLOGICAL

Given IV

Talimogene Laherparepvec

Intervention Type: BIOLOGICAL

Given IM

Interventions

Panitumumab

Given IV

Intervention Type: BIOLOGICAL

Talimogene Laherparepvec

Given IM

Intervention Type: BIOLOGICAL

Other Intervention Names

ABX-EGF; ABX-EGF Monoclonal Antibody; ABX-EGF, Clone E7.6.3; MoAb ABX-EGF; Monoclonal Antibody ABX-EGF; Vectibix; 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

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed squamous cell carcinoma of the skin (SCCS) that is a) locally advanced or metastatic for which curative surgery or radiation would be difficult or impossible, or b) recurrent after initial surgery, chemotherapy, or radiation therapy, or c) considered to have aggressive features including the following: tumors 2 cm or more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes. Patients may have had prior surgical interventions or been treated with investigational agents with residual or recurrent disease
• Tumor suitable for direct or ultrasound-guided injection defined as at least one cutaneous, subcutaneous, or nodal lesion, or aggregate of lesions, >= 10 mm in diameter
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• No prior treatment with panitumumab or talimogene laherparepvec for advanced disease
• Prior surgery or radiation is allowed if there is documented progression in the radiated/resected area or elsewhere by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v) 1.1
• Measurable disease by RECIST criteria v 1.1
• Patients with a history of hematologic or solid organ transplant will be considered if they do not require high dose steroids or high dose immunosupressants for disease control or control of transplant rejection, and have adequate hematologic, renal, and hepatic function as specified below. Current medications must be reviewed with transplant pharmacy team to exclude potentially serious interactions and case discussed with the study principal investigator (PI)
• Second primary malignancy only if treatment would interfere with the patient?s participation in this trial in the opinion of the treating physician. Clear exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g., in situ carcinoma of the cervix) and, 3) additional skin cancers that have been definitively treated by surgery and/or radiation. Patients with chronic lymphocytic leukemia will be allowed if their blood counts are within acceptable hematologic parameters and if they are not currently requiring cytotoxic or biologic anticancer treatment (supportive treatment such as intravenous immunoglobulin [IVIG] is permitted)
• Patients with autoimmune disorders will be considered if they do not require high dose steroids or other immunosuppressants for disease control. Prednisone in daily doses up to 10 mg and inhaled steroids are acceptable
• Absolute neutrophil count (ANC) >= 1500/uL
• Platelet count >= 100,000/mm^2
• Hemoglobin >= 9 g/dL
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN); if patient has conditions of congenital hyperbilirubinemia, then patient must have isolated hyperbilirubinemia (e.g., no other liver function test abnormalities) with maximum bilirubin < 2 x institutional ULN
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x institutional ULN in absence of liver metastases; =< 5 x ULN in presence of liver metastases
• Alkaline phosphatase < 2.5 x institutional ULN
• Creatinine < 1.5 x institutional ULN or calculated creatinine clearance >= 60 mL/min as estimated using the Cockcroft-Gault formula

Exclusion Criteria

• Pregnant women. Women of childbearing age must be willing to undergo a pregnancy test prior to therapy and to use adequate contraception (e.g., hormonal or barrier method of contraception or abstinence) for the duration of the study and 6 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Menopausal status will be defined as one or more of successful hysterectomy, bilateral tubal ligation or bilateral oophorectomy, amenorrhea >= 12 consecutive months without another cause, or a documented serum follicle stimulating hormone (FSH) >= 35 mIU/mL
• Tumor not suitable for direct or ultrasound-guided injection
• Prior treatment with talimogene laherparepvec for advanced disease
• Patients with active, uncontrolled infections including active herpetic infections or chronic herpetic infections requiring anti-viral therapy (e.g., acyclovir)
• Patients without adequate organ function as documented above
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab, talimogene laherparepvec or other agents used in the study
• History of interstitial pneumonitis, pulmonary fibrosis, or evidence of interstitial pneumonitis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: lead

Responsible Party

CINJRegulatory

Principal Investigator is deceased - Professor and Chief of Melanoma and Soft Tissue Sarcoma

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adam C Berger, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

New York University Langone Medical Center

New York, New York, United States

NYU Langone Medical Center (Tisch Hospital)

New York, New York, United States

Duke University Medical Center - Duke Cancer Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: ICF 1

View Document

Other Identifiers

NCI-2019-06083

Identifier Type: REGISTRY

Identifier Source: secondary_id

Pro2018002628

Identifier Type: -

Identifier Source: secondary_id

091804

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro2018002628

Identifier Type: -

Identifier Source: org_study_id