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

Phase 1
Recruiting
Conditions
Advanced Solid Malignancies
Interventions
Registration Number
NCT06028074
Lead Sponsor
Georgiamune Inc
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).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
111
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Intravenous administration of GIM-122GIM122GIM-122
Primary Outcome Measures
NameTimeMethod
Recommended Phase 2 Dose [RP2D] of GIM-12218 Months

To identify Recommended Phase 2 Dose \[RP2D\] of GIM-122

Maximum tolerated dose [MTD] of GIM-12218 months

To identify maximum tolerated dose \[MTD\] of GIM-122

Overall response rate (ORR) -Part B of the study36 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-12218 months

To identify dose limiting toxicities \[DLT\] with GIM-122

Anti-tumor activity of GIM-12236 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 tolerability36 months

To assess incidence and severity of AE / SAEs and tolerability assessed by CTCAE grading

Secondary Outcome Measures
NameTimeMethod
Best overall response (BOR)36 months

To preliminarily evaluate BOR in patients with advanced malignant tumors

Overall survival (OS) rates at 12 months36 months

To preliminarily evaluate OS in patients with advanced malignant tumors at 12 Months

Time of peak plasma concentration (Tmax)36 months

To preliminarily evaluate Tmax in patients with advanced malignant tumors

Overall Response Rate (ORR) - Part A of the study36 months

To preliminarily evaluate ORR in patients with advanced malignant tumors

Tumor expression of immunological markers36 months

To analyze tumor expression of immunological markers

Area under the plasma concentration versus time curve (AUC)36 months

To preliminarily evaluate the AUC in patients with advanced malignant tumors

Peak Plasma Concentration (Cmax)36 months

To preliminarily evaluate Cmax in patients with advanced malignant tumors

Progression-free survival (PFS)36 months

To preliminarily evaluate PFS in patients with advanced malignant tumors

Duration of response (DOR)36 months

To preliminarily evaluate DOR in patients with advanced malignant tumors

Disease control rate (DCR)36 months

To preliminarily evaluate DCR in patients with advanced malignant tumors

Trial Locations

Locations (11)

The Angeles Clinic and Research Institute

🇺🇸

Los Angeles, California, United States

USC/Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

UCLA Hematology/Oncology

🇺🇸

Los Angeles, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Florida Cancer Specialists

🇺🇸

Sarasota, Florida, United States

Norton Cancer Institute

🇺🇸

Louisville, Kentucky, United States

Rutgers Cancer Institute of NJ

🇺🇸

New Brunswick, New Jersey, United States

Tennessee Oncology, PLLC

🇺🇸

Nashville, Tennessee, United States

Texas Oncology - Baylor Sammons Cancer Center

🇺🇸

Dallas, Texas, United States

NEXT Oncology Dallas

🇺🇸

Irving, Texas, United States

Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

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