Clinical trial NCT04163952: Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin
Official title: A Phase 1 Study of Talimogene Laherparepvec and Panitumumab in Patients With Locally Advanced Squamous Cell Carcinoma of the Skin (SCCS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Locally Advanced Skin Squamous Cell Carcinoma
Metastatic Skin Squamous Cell Carcinoma
Recurrent Skin Squamous Cell Carcinoma
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-11-15
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Up to 30 days
measure: Response Rate to Panitumumab as Measured by Evaluation of the Criteria in Solid Tumors (RECIST) 1.1.
timeFrame: Up to two years
Secondary outcomes:
measure: Best Overall Response Rate (ORR) of Participants From Start to Progression of Disease
timeFrame: Up to two years
measure: Durable Response Rate Based on Simons Two-stage Design
timeFrame: Up to two years
measure: Duration of Response Based on Simons Two-stage Design
timeFrame: Time from initial response until document progression up to two years
measure: Progression-free Survival (PFS) to Assess Participants Progressive Free-survival
timeFrame: From date of enrollment to the date of death or progression, whichever occurred earlier assessed up to 2 years
measure: Change in Overall Survival (OS) Measured by the Kaplan-Meier
timeFrame: From date of enrollment to the date of death or date last known alive, whichever comes first, assessed up to assessed up to two years
measure: Mutation Load in Tumor Tissue Measured by Next Generation Sequencing
timeFrame: Up to two years
measure: Deoxyribonucleic Acid Mutation Signature in Tumor Tissue
timeFrame: Up to two years
measure: Messenger Ribonucleic Acid Signature in Tumor Tissue Measured by Nanostring Technology
timeFrame: Up to two years
measure: Immune Cell Populations in Tumor Tissue
timeFrame: Up to two years
measure: Immune Cell Populations Peripheral Blood as Measured by Flow Cytometry
timeFrame: Up to two years
measure: Expression of Cytokines in Tumor Tissue
timeFrame: Up to two years
measure: Expression of Cytokines in Peripheral Blood
timeFrame: Up to two years
measure: Pathologic Complete Response Rate
timeFrame: Up to two years
measure: Time to Resectability
timeFrame: Up to two years
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center (Tisch Hospital)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center - Duke Cancer Center
state: North Carolina
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Adam C Berger, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References: