gi-101 as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy in advanced solid tumors

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Renal Cell Carcinoma; Urinary Bladder Cancer; Melanoma; Sarcoma; Microsatellite Stable Colorectal Carcinoma; Merkel Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Cervical Cancer; Vaginal Cancer; Vulvar Cancer

Summary: the purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of gi-101/gi-101a as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy (rt) over a range of advanced and/or metastatic solid tumors.

this is a phase 1/2, open-label, dose-escalation and expansion study to evaluate the safety, tolerability and anti-tumor effect of gi-101/gi-101a as a single agent or in combination with pembrolizumab, lenvatinib or local rt over a range of advanced and/or metastatic solid tumors. this study will comprise six parts. * part a: dose-escalation and expansion cohorts of gi-101 monotherapy * part b: dose-escalation and expansion cohorts of gi-101 plus pembrolizumab * part c: dose-optimization and expansion cohorts of gi-101 plus lenvatinib * part d: dose-optimization and expansion cohorts of gi-101 plus local rt * part e: dose-escalation and expansion cohorts of gi-101a monotherapy * part f: dose-escalation and expansion cohorts of gi-101a plus pembrolizumab gi-101/gi-101a is a novel bi-specific fc fusion protein containing the cd80 ectodomain as an n-terminal moiety and an interleukin (il)-2 variant as a c-terminal moiety configurated via a human immunoglobulin g4 (igg4) fc. gi-101a is an abbreviation of advanced gi-101 with an improved formulation for manufacture consistency. drug information available for: pembrolizumab (https://www.keytrudahcp.com), lenvatinib (http://www.lenvima.com)

Eligibility criteria:
key inclusion criteria: * males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening. * has adequate organ and marrow function as defined in protocol. * measurable disease as per recist v1.1. * ecog performance status 0-1. * adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to grade ≤1, except alopecia and grade 2 peripheral neuropathy. * hiv infected patients must be on anti-retroviral therapy (art) and have a well-controlled hiv infection/disease as defined in protocol. key exclusion criteria: * has known active cns metastases and/or carcinomatous meningitis. * an active second malignancy * has active or a known history of hepatitis b or known active hepatitis c virus infection. * has active tuberculosis or has a known history of active tuberculosis * active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration. * history of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis. * has an active autoimmune disease that has required systemic treatment in past 2 years. * previous immunotherapies related to mode of action of gi-101. * has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to cycle 1 day 1. * administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment. * radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy (except part d). * administration of a live, attenuated vaccine within 4 weeks before cycle 1 day 1. * known hypersensitivity to any of the components of the drug products and/or excipients of gi-101, pembrolizumab or lenvatinib. other protocol defined inclusion exclusion criteria may apply

Keywords: gi-101/gi-101a cd80-igg4 fc-il2 variant immunotherapy il-2 interleukin-2 pembrolizumab lenvatinib radiotherapy