study of pf-07263689 in participants with selected advanced solid tumors

Conditions: Renal Cell Cancer; Melanoma; Non-Small-Cell Lung Cancer; Hepatocellular Cancer; Bladder Cancer; Sarcoma; Head and Neck Cancer; Colorectal Cancer; Ovarian Cancer; Squamous Cell Carcinoma

Summary: this is a first-in-human, phase 1, open label, multicenter, multiple dose, dose escalation and expansion study intended to evaluate the safety, viral load kinetics and shedding, pharmacodynamic, and anti-tumor activity of pf-07263689, either alone or in combination with sasanlimab (an investigational anti-programmed cell death protein 1 \[pd-1\] antibody), in patients with selected locally advanced or metastatic solid tumors who have exhausted all available standard of care therapies available to them. the study consists of 2 parts: part 1 dose escalation for pf-07263689 monotherapy (part 1a) and in combination with sasanlimab (part 1b), followed by part 2 dose expansion for the combination therapy.


Eligibility criteria:
inclusion criteria: * histological or cytological diagnosis of locally advanced or metastatic solid tumors known to have approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents * have exhausted (or refuse) all available standard of care therapy (e.g., including anti-pd1/programmed death ligand 1 \[pdl1\] if applicable) or for whom no standard therapy is available for their tumor type * patients with prior anti-pd1/pdl1 must have documentation of primary or secondary resistance to last prior anti-pd1/pdl1 therapy according to immunotherapy resistance committee (sitc) (kluger et al, 2020) * have at least 1 measurable lesion by recist 1.1 that has not been previously irradiated (for part 2 only) * have recently obtained archival tumor tissue sample available, or undergo de novo tumor biopsy * eastern cooperative oncology group (ecog) ps 0-1 * adequate hematologic, renal, and liver functions * dose escalation (part 1a and 1b): any advanced or metastatic solid tumor fulfilling other relevant eligibility criteria. * dose expansion (part 2): tumor specific cohorts (nsclc, rcc, melanoma, mss crc) must have received prior approved therapies (part 2) exclusion criteria: * other active malignancy * recent major surgery * systemic anticancer therapy and chemotherapy within protocol-defined washout period * known or suspected hypersensitivity to prior treatment with any vaccinia oncolytic, pox virus, or antiviral agents within the past 10 years * current or history of myocarditis or congestive heart failure (new york heart association \[nyha\] iii-iv); unstable angina; or serious uncontrolled arrhythmia or recent myocardial infarction * active or history of interstitial lung disease (ild)/pneumonitis * patients requiring chronic systemic immunosuppressants * history of severe immune mediated side effect that was considered related to prior immune modulatory therapy and requiring immunosuppressive therapy * known symptomatic brain metastases requiring steroids * history of or ongoing severe inflammatory skin conditions or severe eczema having required medical treatment * any prior or planned organ transplant * presence of any open, active wound requiring treatment

Keywords: advanced malignancies