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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Advanced Solid Malignancies

Intervention / Treatment
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* Drug: GIM122


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Part A: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), Part B: Dose Expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous administration of GIM-122<br>GIM-122 | Drug: GIM122<br>* GIM-122 administered IV once every 3 weeks<br>* Other names: GIM-122;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities [DLT] with GIM-122 | To identify dose limiting toxicities [DLT] with GIM-122 | 18 months | 
| Maximum tolerated dose [MTD] of GIM-122 | To identify maximum tolerated dose [MTD] of GIM-122 | 18 months | 
| Recommended Phase 2 Dose [RP2D] of GIM-122 | To identify Recommended Phase 2 Dose [RP2D] of GIM-122 | 18 Months | 
| Overall response rate (ORR) -Part B of the study | To identify overall response rate (ORR) in patients with advanced malignant tumors who are refractory/ resistant to PD-1 and PD-L1 therapy | 36 months | 
| Anti-tumor activity of GIM-122 | To assess anti-tumor activity of GIM-122 as a single agent in patients with advanced malignant tumors who are refractory/ resistant to PD-1 and PD-L1 therapy | 36 months | 
| Incidence and severity of AE / SAEs and tolerability | To assess incidence and severity of AE / SAEs and tolerability assessed by CTCAE grading | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | To preliminarily evaluate the AUC in patients with advanced malignant tumors | 36 months | 
| Peak Plasma Concentration (Cmax) | To preliminarily evaluate Cmax in patients with advanced malignant tumors | 36 months | 
| Time of peak plasma concentration (Tmax) | To preliminarily evaluate Tmax in patients with advanced malignant tumors | 36 months | 
| Overall Response Rate (ORR) - Part A of the study | To preliminarily evaluate ORR in patients with advanced malignant tumors | 36 months | 
| Duration of response (DOR) | To preliminarily evaluate DOR in patients with advanced malignant tumors | 36 months | 
| To preliminarily evaluate DOR in patients with advanced malignant tumors | To preliminarily evaluate DCR in patients with advanced malignant tumors | 36 months | 
| Best overall response (BOR) | To preliminarily evaluate BOR in patients with advanced malignant tumors | 36 months | 
| Progression-free survival (PFS) | To preliminarily evaluate PFS in patients with advanced malignant tumors | 36 months | 
| Overall survival (OS) rates at 12 months | To preliminarily evaluate OS in patients with advanced malignant tumors at 12 Months | 36 months | 
| Tumor expression of immunological markers | To analyze tumor expression of immunological markers | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumor, advanced malignancies, GIM-122