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

NCT06425926 | Recruiting Phase 1 FDA Drug

• 1 other identifier: GIM531-CT01
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 11

Brief 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).

Conditions

Melanoma Stage IV; Solid Tumor

Keywords

PD-1 resistance; PD-1 resistant/refractory; AKT3

Outcome Measures

Primary Outcomes (2)

• 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

• Dose limiting toxicities (DLT) with GIM-531

  To identify dose limiting toxicities with GIM-531

  21 days

Secondary Outcomes (10)

• Maximum plasma concentration (Cmax)

  Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

• Time to maximum plasma concentration (Tmax)

  Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

• Area under the plasma concentration versus time curve (AUC)

  Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

• Objective response rate (ORR)

  From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)

• Best overall response (BOR)

  From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)

Study Arms (2)

Phase 1 Single Agent

EXPERIMENTAL

GIM-531 administered orally daily

Drug: GIM-531

Phase 2 Combination Treatment

EXPERIMENTAL

GIM-531 administered orally daily in combination with anti-PD-1 therapy

Drug: GIM-531; Drug: Anti-PD-1 monoclonal antibody

Interventions

GIM-531 DRUG

GIM-531 administered orally daily

Phase 1 Single Agent; Phase 2 Combination Treatment

Anti-PD-1 monoclonal antibody DRUG

Continued treatment with anti-PD-1 therapy

Phase 2 Combination Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 study drug treatment 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
• NSCLC: Participants must have locally advanced/unresectable or metastatic NSCLC. Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
• TNBC: Participants must have locally advanced unresectable, recurrent, or metastatic TNBC. Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
• Ovarian Cancer: Participants must have locally advanced unresectable, recurrent, or metastatic ovarian cancer. Participants must have platinum-resistant ovarian cancer defined as disease recurrence or within 6 months after the last administration of platinum-based chemotherapy. Participants must have received no more than 1 line of therapy after development of platinum resistance. Maintenance treatment with Poly(ADP-ribose) polymerase inhibitors (PARPi) or bevacizumab are not counted as separate lines of therapy.
• Tumors with AKT3 mutation/amplification: Participants must have a locally advanced unresectable, recurrent, or metastatic solid malignancy. Participants with known AKT3 mutation/amplification based on next generation sequencing (NGS) performed per local standard of care.
• Have confirmed unresectable Stage III or metastatic Stage IV cutaneous melanoma, NSCLC, or RCC that has radiographically progressed (as confirmed by imaging assessed by the Investigator) on an approved single-agent or combination anti-PD-1 therapy
• Must have received the anti-PD-1 therapy containing regimen as the latest line of treatment and be eligible to restart or to continue anti-PD-1 therapy in combination with GIM-531
• BRAF wild-type melanoma or RCC: Participants must have received no more than 2 prior lines of therapy in the advanced/metastatic setting

You may not qualify if:

• Has known leptomeningeal disease, spinal cord compression, or brain metastases, except participants with the following:
• Brain metastases that have been treated 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 12 months (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.

Sponsors & Collaborators

• Georgiamune Inc: lead

Study Sites (11)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

RECRUITING

Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate

Los Angeles, California, 90025, United States

RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana

Billings, Montana, 59102, United States

RECRUITING

Weill Cornell Medicine - New York Presbyterian Hospital

New York, New York, 10065, United States

RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

RECRUITING

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Jayadev Sureddi, CBCC CRO

CONTACT

(661) 616-6453; jayadev.sureddi@cbcc.global

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 23, 2024
• Study Start: May 9, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)