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
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Georgiamune Inc
- Enrollment
- 111
- Locations
- 11
- Primary Endpoint
- Recommended Phase 2 Dose [RP2D] of GIM-122
Overview
Brief 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.
Detailed Description
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent
- •ECOG performance status 0-
- •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
- •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
Arms & Interventions
Intravenous administration of GIM-122
GIM-122
Intervention: GIM122 (Drug)
Outcomes
Primary Outcomes
Recommended Phase 2 Dose [RP2D] of GIM-122
Time Frame: 18 Months
To identify Recommended Phase 2 Dose \[RP2D\] of GIM-122
Maximum tolerated dose [MTD] of GIM-122
Time Frame: 18 months
To identify maximum tolerated dose \[MTD\] of GIM-122
Overall response rate (ORR) -Part B of the study
Time Frame: 36 months
To identify overall response rate (ORR) in patients with advanced malignant tumors who are refractory/ resistant to PD-1 and PD-L1 therapy
Dose limiting toxicities [DLT] with GIM-122
Time Frame: 18 months
To identify dose limiting toxicities \[DLT\] with GIM-122
Anti-tumor activity of GIM-122
Time Frame: 36 months
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
Incidence and severity of AE / SAEs and tolerability
Time Frame: 36 months
To assess incidence and severity of AE / SAEs and tolerability assessed by CTCAE grading
Secondary Outcomes
- Best overall response (BOR)(36 months)
- Overall survival (OS) rates at 12 months(36 months)
- Time of peak plasma concentration (Tmax)(36 months)
- Overall Response Rate (ORR) - Part A of the study(36 months)
- Tumor expression of immunological markers(36 months)
- Area under the plasma concentration versus time curve (AUC)(36 months)
- Peak Plasma Concentration (Cmax)(36 months)
- Progression-free survival (PFS)(36 months)
- Duration of response (DOR)(36 months)
- Disease control rate (DCR)(36 months)