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.
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