Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase 1/2, Open-label, Multi-center Study of the Safety, Tolerability, and Efficacy of GIM-531 as a Single Agent and in Combination With Anti-PD-1 in Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06425926
• Other study ID #: GIM531-CT01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 9, 2024
• Est. completion date: November 2026

Study information

• Verified date: June 2024
• Source: Georgiamune Inc
• Contact: Jayadev Sureddi, CBCC CRO
• Phone: (661) 616-6453
• Email: jayadev.sureddi[@]cbcc.global
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GIM-531 is a first-in-class, orally bioavailable small molecule that is being developed for the treatment of advanced solid tumors as a single agent and rescue therapy. GIM-531 exhibits its primary effect through selective inhibition of regulatory T-cells (Tregs).

Description:

GIM531-CT01 is a Phase 1/2 open label, first-in-human, multicenter study. The Phase 1 portion will include a dose escalation with GIM-531 administered as a single agent. Additionally, there will be a dose expansion portion at the safety-cleared dose levels with participants allocated 1:1 within the proposed therapeutic range to accrue additional data for determining the safety profile, pharmacokinetics (PK) profile, pharmacodynamic (PD) effects and early anti-tumor activity of GIM-531. In Phase 2, GIM-531will be administered to participants with advanced/metastatic cutaneous melanoma who have progressed following treatment with an anti-PD-1 therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: November 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Written informed consent

• Cytologically or histologically confirmed locally advanced or metastatic solid tumor that has progressed on standard therapy or for which no standard therapy exist; or be intolerant of standard therapy

• Have not received an experimental drug within 4 weeks or 5 half-lives (whichever is shorter) of Screening or already be enrolled in a clinical study

• ECOG performance status 0-1

• Laboratory and ECG assessments within 28 days of enrollment including acceptable cardiac, renal, and hepatic functions

• Agree to baseline core needle biopsy or archival (within 12 months of screening) tumor submission; Note: Participants whose only site(s) of disease are in areas considered moderate or high risk for biopsy complications may be enrolled without a fresh biopsy upon Sponsor approval.

• Non pregnant participants; female participants of child bearing potential with non-sterile partners agree to use an effective form of contraception from the time of first dose of study drug (or 14 days prior to first dose for oral contraception) until 7 months after the last dose of study drug. Effective forms of contraception include hormonal (injection or oral), double barrier method, or intrauterine device. Non-sterile male participants with sexual partners of childbearing potential agree to use a barrier contraception method and agree to not donate sperm from the time of first dose of study drug until 4 months after the last dose of study drug.

• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

Phase 2 Specific Inclusion Criteria (in addition to above inclusion criteria):

• Have confirmed unresectable Stage III or metastatic Stage IV cutaneous melanoma that has radiographically progressed (as confirmed by imaging assessed by the Investigator) on an approved first-line single-agent or combination anti-PD-1 therapy

• Receiving anti-PD-1 therapy as their first line of treatment at the time of enrollment and amenable to continuing anti-PD-1 therapy during the study

Key Exclusion Criteria:

• Ongoing >Grade 1 toxicity from prior therapy according to Common Terminology Criteria for Adverse Events v5.0 (Note: Grade 2 alopecia and Grade 2 sensory neuropathy are not exclusionary)

• Has melanoma with documented BRAF mutation (Phase 2 only)

• Has known brain metastases, except participants with the following:

• Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the first administration of study drug; Note: Participants receiving steroids for brain metastases must be either off steroids or on a stable, or decreasing dose, of <10 mg daily of prednisone (or equivalent) in order to be eligible for enrollment; and

• No ongoing neurological symptoms related to the anatomic location of the brain metastases.

Note: Neurological symptoms that are considered sequelae to treatment for brain metastases are allowed.

• Has known structural cardiac disease

• Has known serious arrythmia, serious dysrhythmia, history of long QT syndrome, or clinically relevant cardiac conduction abnormalities

• Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

• At time of screening, is receiving systemic steroid therapy (greater than or equal to 10 mg/day of prednisone or equivalent) or is taking any immunosuppressive therapy; Note: Use of topical, inhaled, nasal, or ophthalmic steroids is allowed.

• Has active and clinically significant bacterial, fungal, or viral infection, including known hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)

• Has a history of, or currently has, an acquired or primary (congenital) immunodeficiency;

• Has had prior anti-cancer treatment with chemotherapeutic agents or immune modulating agents within <4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study drug.

• Has received a live vaccine within 30 days of first dose of study drug;

• Has had or has planned major surgery within 2 weeks of the first dose of study drug;

• Inability to swallow an oral dose of a medication (eg, oral capsules)

• Is taking medications that are considered strong inducers or inhibitors of CYP2C8 or CYP3A4/5, P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), or sensitive substrates of P-gp and BCRP (Appendix C) that cannot be discontinued at least 1 week prior to first dose of study drug and for the duration of the study.

• Is taking drugs that modify gastric pH, such as proton-pump inhibitors (PPIs) or H2 blockers. Antacids such as calcium carbonate or aluminum hydroxide-based products are permitted.

Related Conditions & MeSH terms

• Melanoma
• Melanoma Stage IV
• Neoplasms
• Solid Tumor

Intervention

Drug:
• GIM-531
GIM-531 administered orally daily
• Anti-PD-1 monoclonal antibody
Continued treatment with anti-PD-1 therapy

Locations

Country	Name	City	State
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana	Billings	Montana
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Georgiamune Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events (AEs) / serious adverse events (SAEs) and tolerability	To assess incidence and severity of AE / SAEs and tolerability assessed by CTCAE grading	Through study completion, an average of 1 year
Primary	Dose limiting toxicities (DLT) with GIM-531	To identify dose limiting toxicities with GIM-531	21 days
Secondary	Maximum plasma concentration (Cmax)	To preliminarily evaluate the Cmax in patients with advanced solid tumors	Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
Secondary	Time to maximum plasma concentration (Tmax)	To preliminarily evaluate Tmax in patients with advanced solid tumors	Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
Secondary	Area under the plasma concentration versus time curve (AUC)	To preliminarily evaluate the AUC in patients with advanced solid tumors	Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
Secondary	Objective response rate (ORR)	To identify objective response rate in patients with advanced solid tumors	From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)
Secondary	Best overall response (BOR)	To preliminarily evaluate BOR in patients with advanced solid tumors	From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)
Secondary	Duration of response (DOR)	To preliminarily evaluate DOR in patients with advanced solid tumors	From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)
Secondary	Disease control rate (DCR)	To preliminarily evaluate DCR in patients with advanced solid tumors	From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)
Secondary	Progression-free survival (PFS)	To preliminarily evaluate PFS in patients with advanced solid tumors	From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)
Secondary	Overall survival (OS) rates	To preliminarily evaluate OS in patients with advanced solid tumors, including 12 month OS	From study enrollment until death from any cause (OS rate assessed at 12 months)
Secondary	Tumor expression of immunological markers	To analyze tumor expression of immunological markers	Cycle 1 Days 1, 2 and 8; Cycle 2 Days 1 and 8; Cycle 3 Day 1 (each Cycle is 14 days)