Safety and Tolerability Study of GIM-122 in Subjects With Advanced Solid Malignancies

A First-in-Human, Open-Label, Phase 1/2 Dose-Escalation With Enrichment and Dose-Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of GIM-122 as a Single Agent in Adult Subjects With Advanced Solid Malignancies

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).

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).