## Protocol Section
### Identification Module
**NCT ID:** NCT06425926

**Brief Title:** Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors

**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

#### Organization Study ID Info
**ID:** GIM531-CT01
#### Organization
**Class:** INDUSTRY
**Full Name:** Georgiamune Inc
### Status Module
#### Completion Date
**Date:** 2026-11

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-30

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Georgiamune Inc

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

### Description Module

**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).

**Detailed 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.

### Conditions Module

**Conditions:**

- Melanoma Stage IV

- Solid Tumor

**Keywords:**

- PD-1 resistance

- PD-1 resistant/refractory

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 84

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** GIM-531 administered orally daily

**Intervention Names:**

- Drug: GIM-531

**Label:** Phase 1 Single Agent

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: GIM-531

- Drug: Anti-PD-1 monoclonal antibody

**Label:** Phase 2 Combination Treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Phase 1 Single Agent

- Phase 2 Combination Treatment

**Description:** GIM-531 administered orally daily

**Name:** GIM-531

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Phase 2 Combination Treatment

**Description:** Continued treatment with anti-PD-1 therapy

**Name:** Anti-PD-1 monoclonal antibody

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** Incidence and severity of adverse events (AEs) / serious adverse events (SAEs) and tolerability

**Time Frame:** Through study completion, an average of 1 year

**Description:** To identify dose limiting toxicities with GIM-531

**Measure:** Dose limiting toxicities (DLT) with GIM-531

**Time Frame:** 21 days

#### Secondary Outcomes

**Description:** To preliminarily evaluate the Cmax in patients with advanced solid tumors

**Measure:** Maximum plasma concentration (Cmax)

**Time Frame:** Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

**Description:** To preliminarily evaluate Tmax in patients with advanced solid tumors

**Measure:** Time to maximum plasma concentration (Tmax)

**Time Frame:** Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

**Description:** To preliminarily evaluate the AUC in patients with advanced solid tumors

**Measure:** Area under the plasma concentration versus time curve (AUC)

**Time Frame:** Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

**Description:** To identify objective response rate in patients with advanced solid tumors

**Measure:** Objective response rate (ORR)

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

**Description:** To preliminarily evaluate BOR in patients with advanced solid tumors

**Measure:** Best overall response (BOR)

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

**Description:** To preliminarily evaluate DOR in patients with advanced solid tumors

**Measure:** Duration of response (DOR)

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

**Description:** To preliminarily evaluate DCR in patients with advanced solid tumors

**Measure:** Disease control rate (DCR)

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

**Description:** To preliminarily evaluate PFS in patients with advanced solid tumors

**Measure:** Progression-free survival (PFS)

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

**Description:** To preliminarily evaluate OS in patients with advanced solid tumors, including 12 month OS

**Measure:** Overall survival (OS) rates

**Time Frame:** From study enrollment until death from any cause (OS rate assessed at 12 months)

**Description:** To analyze tumor expression of immunological markers

**Measure:** Tumor expression of immunological markers

**Time Frame:** Cycle 1 Days 1, 2 and 8; Cycle 2 Days 1 and 8; Cycle 3 Day 1 (each Cycle is 14 days)

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jayadev.sureddi@cbcc.global

**Name:** Jayadev Sureddi, CBCC CRO

**Phone:** (661) 616-6453

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Bakersfield

**Contacts:**

***Contact 1:***

- **Email:** nward@cbccusa.com

- **Name:** Nicole Ward

- **Phone:** 661-862-8548

- **Role:** CONTACT

**Country:** United States

**Facility:** Comprehensive Blood and Cancer Center

**State:** California

**Status:** RECRUITING

**Zip:** 93309

**Location 2:**

**City:** Billings

**Contacts:**

***Contact 1:***

- **Email:** matt.adler@imail.org

- **Name:** Matt Adler

- **Phone:** 406-238-6894

- **Role:** CONTACT

**Country:** United States

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

**State:** Montana

**Status:** RECRUITING

**Zip:** 59102

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018358

- Term: Neuroendocrine Tumors

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

- ID: D000018326

- Term: Nevi and Melanomas

- ID: D000012878

- Term: Skin Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11528

- Name: Melanoma

- Relevance: HIGH

- As Found: Melanoma

- ID: M20495

- Name: Neuroendocrine Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12448

- Name: Nevus, Pigmented

- Relevance: LOW

- As Found: Unknown

- ID: M12446

- Name: Nevus

- Relevance: LOW

- As Found: Unknown

- ID: M20470

- Name: Nevi and Melanomas

- Relevance: LOW

- As Found: Unknown

- ID: M15681

- Name: Skin Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4091

- Name: Neuroendocrine Tumor

- Relevance: LOW

- As Found: Unknown

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

- ID: D000008545

- Term: Melanoma

### Intervention Browse Module - Ancestors

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: HIGH

- As Found: Given

- ID: M4230

- Name: Antibodies, Monoclonal

- Relevance: HIGH

- As Found: Chemotherapy

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000000906

- Term: Antibodies

- ID: D000000911

- Term: Antibodies, Monoclonal

### Misc Info Module

- Version Holder: 2024-05-31
