safety and tolerability study of gim-122 in subjects with advanced solid malignancies

Conditions: Advanced Solid Malignancies

Summary: gim-122 is a first-in-class, humanized immunoglobulin g1 kappa dual functioning monoclonal antibody (dfa). this phase 1 / 2 study plans to evaluate the safety, tolerability, pharmacokinetics and clinical efficacy of intravenous (iv) administration of gim-122 in adults with advanced malignancies.

this is a phase 1/2, open label, first-in-human (fih), multicenter, dose escalation study with enrichments and dose expansion cohorts at rp2d, designed to evaluate the safety, tolerability, pk, pharmacodynamics, and preliminary antitumor activity of gim-122 administered as a single agent in adults with advanced solid malignancies. this study will be conducted in 2 parts: phase 1 or part a (dose escalation and enrichment) and phase 2 or part b (dose optimization and cohort expansion).

Eligibility criteria:
inclusion criteria: general * written informed consent * ecog performance status 0-1. * laboratory assessment 28 days prior to enrollment for assessment of acceptable cardiac, renal and hepatic functions * recommended double methods of contraception 90-days post treatment cancer specific * histologically or cytologically confirmed locally advanced/unresectable or metastatic solid tumor * received fda approved treatment of pd-1 inhibitor or pd-l1 inhibitor for advance malignant tumors and have progressed/relapsed, are refractory, or intolerant * measurable disease according to response evaluation criteria in solid tumors (recist), version 1.1 * had prior therapy with pd-1/pd-l1 inhibitors. other checkpoint inhibitors (ie, ctla4, lag3) are permitted if they did not lead to treatment discontinuation * no other lines of therapy that are available exclusion criteria: general * enrolled in any other interventional clinical trial, starting within 4 weeks of the first dose of gim-122 and throughout the duration of the study, or is receiving other therapy directed at their malignancy * women who are pregnant or breastfeeding * history of cardiac issues, pulmonary embolism, active and clinically significant bacterial, fungal, or viral infection ≤ 6 months prior to dosing * contraindications to the imaging assessments or other study procedures that subjects will undergo or any medical or social condition that, in the opinion of the investigator, might place a subject at an increased risk, affect compliance, or confound safety or other clinical study data interpretation cancer specific * current second malignancy at other sites * leptomeningeal disease * spinal cord compression * symptomatic or new or enlarging central nervous system (cns) metastases treatment-specific exclusion criteria * ongoing toxicity \> grade 1 from prior therapy according to common terminology criteria for adverse events (ctcae) v 5.0 * has undergone a major surgery \< 1 month prior to administration of gim-122 * has received radiation therapy within 2 weeks prior to administration of gim-122 * has undergone or is anticipated to undergo organ transplantation including allogeneic or autologous stem cell transplantation at any time * has received systemic anti-cancer therapy within 2 weeks and cytotoxic agents that have a major delayed toxicity within 4 weeks, of the first dose of gim-122 * prior treatment with other immune modulating agents within \< 4 weeks prior to the first dose of gim-122. * has a diagnosis of immunodeficiency, either primary or acquired * has received treatment with systemic steroids or any form of immunosuppressive therapy within 14 days prior to administration of gim-122 * has active or prior history of autoimmune disease, including ulcerative colitis and crohn's disease, or any condition that requires systemic steroids. * has a known severe intolerance to or hypersensitivity reactions to monoclonal antibodies, fc-bearing proteins, or iv immunoglobulin preparations; prior history of human anti-human antibody response; known allergy to any of the study medications, or excipients in the various formulations of any agent. * has received live vaccines within 30 days of study initiation (inactivated vaccines are allowed; seasonal vaccines should be up to date \> 30 days prior to administration of gim-122).

Keywords: solid tumor advanced malignancies gim-122