Clinical trial NCT06028074: Safety and Tolerability Study of GIM-122 in Subjects With Advanced Solid Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Malignancies
Keywords: solid tumor
advanced malignancies
GIM-122
Lead sponsor: Georgiamune Inc
Sponsor class: INDUSTRY
First posted: 2023-09-07
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Part A: Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), Part B: Dose Expansion
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Dose limiting toxicities [DLT] with GIM-122
timeFrame: 18 months
measure: Maximum tolerated dose [MTD] of GIM-122
timeFrame: 18 months
measure: Recommended Phase 2 Dose [RP2D] of GIM-122
timeFrame: 18 Months
measure: Overall response rate (ORR) -Part B of the study
timeFrame: 36 months
measure: Anti-tumor activity of GIM-122
timeFrame: 36 months
measure: Incidence and severity of AE / SAEs and tolerability
timeFrame: 36 months
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 36 months
measure: Peak Plasma Concentration (Cmax)
timeFrame: 36 months
measure: Time of peak plasma concentration (Tmax)
timeFrame: 36 months
measure: Overall Response Rate (ORR) - Part A of the study
timeFrame: 36 months
measure: Duration of response (DOR)
timeFrame: 36 months
measure: Disease control rate (DCR)
timeFrame: 36 months
measure: Best overall response (BOR)
timeFrame: 36 months
measure: Progression-free survival (PFS)
timeFrame: 36 months
measure: Overall survival (OS) rates at 12 months
timeFrame: 36 months
measure: Tumor expression of immunological markers
timeFrame: 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of NJ
state: New Jersey
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Irving
country: United States
facility: NEXT Oncology Dallas
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: The Angeles Clinic and Research Institute
name: Omid Hamid, MD
role: PRINCIPAL_INVESTIGATOR
References: