Inclusion criteria, exclusion criteria and study summary
All patients: • Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol. • Male or female ≥ 18 years of age at the time of informed consent. • At least one measurable and injectable (including use of image-guided injection) tumor of ≥ 1 cm in longest diameter. • Females of childbearing potential must have negative beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG. • Female subjects of childbearing potential must be willing to use a highly effective method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study and 3 months after last dose of study medication (see Section 6.3.7). • Male subjects of reproductive potential must agree to use a highly effective method of contraception during sexual contact with females of childbearing potential starting with the first dose of study medication and 3 months after the last dose of study therapy (see Section 6.3.7). • Adequate hematologic function including: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Platelet count ≥ 100 x 109/L - Hemoglobin ≥ 9 g/dL (without requiring transfusion or hematologic growth factor) • Adequate hepatic function including: - Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) - Aspartate amino transferase (AST) ≤ 2.5 x ULN - Alanine amino transferase (ALT) ≤ 2.5 x ULN • Adequate renal function including: - Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50cc/min • Prothrombin time (PT) ≤ 1.5 x ULN (or international normalization ratio [INR] ≤ 1.3) and partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN Phase 1 patients only: • Patients with advanced/metastatic solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for which there is no standard therapy preferred to enrollment in a clinical trial. • ECOG performance status ≤ 2 Phase 2 patients only: • ECOG performance status 0 - 1 • Measurable disease based upon RECIST v1.1 • Life expectancy of at least 3 months • Patients with STS: Diagnosis of primary soft tissue sarcoma (T2a or T2b disease), superficial or deep tumor, Grade 1, 2, 3 or 4, tumor located on the upper/lower extremity or trunk, or locally recurrent disease for which local radiation therapy followed by surgery are the standard of care, tumor size at least ≥ 5 cm in the longest diameter as measured by CT scan or MRI for which radiation is feasible • Patients with TNBC: Initial diagnosis of TNBC by central laboratory and according to ASCO/CAP current guidelines, metastatic or locally recurrent inoperable disease; newly obtained tumor biopsy from metastatic site; received either one or two prior systemic treatments for metastatic breast cancer; documented disease progression on the most recent therapy; previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting. • Patients with melanoma: Diagnosis of stage IIIb-IV melanoma, LDH < 1.5 ULN, for whom pembrolizumab therapy is indicated according to a current approved label, and who have not received prior systemic therapy • Patients with NSCLC: Diagnosis of metastatic NSCLC for whom pembrolizumab therapy is indicated according to a current approved label • Patients with NMSC: Histologic or cytologic diagnosis of basal cell carcinoma, squamous cell carcinoma of the skin (vulvar squamous carcinoma, basosquamous carcinoma, and squamous cell carcinoma of unknown primary), basosquamous cell carcinoma of the skin, Merkel cell carcinoma (MCC) or cutaneous T cell lymphoma (CTCL), that is advanced (tumors considered unresectable) or refractory (persistent or recurrent disease with prior therapy including either: surgery, radiation, intralesional/topical therapy or systemic therapy) • Patients with Melanoma, NSCLC, TNBC and NMSC: Willingness to comply with the pembrolizumab risk minimization plan (e.g., be educated about the associated risks and carry and use the Patient Alert Card).
All patients: • Prior treatment with an oncolytic therapy, • Known to have acute or chronic active hepatitis B/C or human immunodeficiency virus (HIV) infection, • Had systemic infection requiring intravenous (IV) antibiotics or other serious infection within 14 days prior to dosing • Immunocompromised patients including those with history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS, or other clinical manifestations of infection with human immunodeficiency viruses. • Evidence of active, known or suspected autoimmune disease or non-infectious pneumonitis, glomerulonephritis, vasculitis or evidence of immune suppression for any reason o Vitiligo, Type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, non-autoimmune hypothyroidism and resolved childhood asthma/atopy are permitted • With active significant herpetic infections or prior complications of HSV-1 infection (e.g. herpetic keratitis or encephalitis), • Requires intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g. acyclovir), • Systemic anti-cancer therapies within 2 weeks of first dose and not recovered (or reached non-clinically significant stability) from all toxicities associated with prior treatments. • Requiring chronic systemic steroid treatment, or any other form of immunosuppressive medication; patients using physiologic replacement doses of hydrocortisone (or equivalent) will be eligible provided it does not exceed 20 mg hydrocortisone (5 mg prednisone) morning dosing and 10 mg hydrocortisone (2.5 mg prednisone) evening dosing; inhaled or local steroid injections are not excluded, • Known active CNS metastases (previously treated brain metastases will be permitted provided they are stable for 4 weeks), • Major surgery ≤ 2 weeks prior to starting study drug • Prior other malignancy that progressed or required active treatment within the last 2 years; exceptions include basal and squamous cell carcinoma of the skin that has had likely curative treatment or in situ cervical cancer • Female who is pregnant or breast-feeding or planning to become pregnant during study treatment and 3 months after the last dose of study treatment Phase 2 patients only: • Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1) or anti-PD-L1, agent • Patients with STS: wide field radiotherapy ≤ 4 weeks or limited field radiation ≤ 2 weeks prior to starting study drug • Patients with melanoma: no ocular or mucosal melanoma • Patients with melanoma, NSCLC, TNBC and NMSC: history of interstitial lung disease • Patients with melanoma, NSCLC, TNBC and NMSC: severe hypersensitivity to another monoclonal antibody.
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