GIM-531 for Solid Tumors

Recruiting at 11 trial locations

Overseen By Jayadev Sureddi, CBCC CRO

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Georgiamune Inc

Must be taking: Anti-PD-1 therapy

Must not be taking: Steroids, Immunosuppressants, PPIs, H2 blockers

Disqualifiers: Cardiac disease, Autoimmune, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

117 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, GIM-531, for individuals with advanced solid tumors. GIM-531 is an oral medication that blocks certain immune cells (Tregs) potentially aiding tumor growth. The trial consists of two parts: one administering GIM-531 alone and another combining it with anti-PD-1 therapy, a type of cancer treatment. It seeks participants whose solid tumors have not responded to standard treatments or who cannot tolerate them. Those with tumors that have grown despite other treatments and have not tried an experimental drug in the past month may find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial requires you to stop taking certain medications, specifically those that are strong inducers or inhibitors of specific enzymes (CYP2C8 or CYP3A4/5) and certain drugs that modify stomach acid, like proton-pump inhibitors. You must discontinue these at least 1 week before starting the study drug and for the duration of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that GIM-531 is in the early stages of testing to determine its safety for people. Specific safety information for this treatment is not yet available. However, as a Phase 1/2 trial, GIM-531 has already undergone safety checks in smaller groups and is now deemed safe enough for larger groups.

This trial tests GIM-531 alone and in combination with another treatment called anti-PD-1 therapy. Anti-PD-1 therapy helps the body's immune system fight cancer. Although specific side effects are not yet known, this combination is being tested to assess its tolerability.

Participants should discuss any potential risks and benefits with their doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for solid tumors, like chemotherapy and radiation, target and kill fast-growing cells but can’t distinguish between healthy and cancerous ones. GIM-531 is unique because it works by enhancing the immune system's natural ability to fight cancer cells, providing a more targeted approach. In combination with anti-PD-1 therapy, GIM-531 could potentially improve the effectiveness of immune-based treatments by blocking the proteins that prevent the immune system from attacking cancer cells. Researchers are excited about GIM-531 because it offers a novel mechanism that might lead to fewer side effects and more personalized treatment options.

What evidence suggests that GIM-531 might be an effective treatment for solid tumors?

Research has shown that GIM-531 may help treat advanced solid tumors by targeting specific immune cells that usually suppress the body's natural ability to fight cancer. This action strengthens the immune system's response against cancer. In studies, patients with advanced tumors who received similar treatments experienced benefits like better disease control and longer survival. In this trial, participants will receive GIM-531 either as a single agent or in combination with anti-PD-1 therapy. Combining GIM-531 with anti-PD-1 therapy, which helps the immune system identify and attack cancer cells, has proven effective for some patients. In trials with similar combination treatments, 16.7% of patients showed noticeable improvement, and 72.2% had their disease under control. These findings suggest that GIM-531, whether used alone or with anti-PD-1 therapy, could effectively treat advanced solid tumors. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including melanoma, that have worsened after standard treatment or who can't tolerate it. They must not have taken experimental drugs recently and should be in good physical condition (ECOG 0-1). Participants need functioning major organs and agree to a tumor biopsy. Women of childbearing age and men must use effective contraception.

Inclusion Criteria

I have signed the consent form.

I haven't taken any experimental drugs recently or am not in another study.

My recent tests show my heart, kidneys, and liver are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose escalation with GIM-531 administered as a single agent to determine safety profile, PK, PD effects, and early anti-tumor activity

21 days

Multiple visits for dose escalation and monitoring

Phase 2 Treatment

GIM-531 administered in combination with anti-PD-1 therapy to participants with advanced/metastatic cutaneous melanoma

Approximately 2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• GIM-531

Trial Overview The study tests GIM-531, an oral drug designed to block certain immune cells (Tregs) that may allow tumors to grow. It's given as a single agent or rescue therapy for those whose cancer has progressed on anti-PD-1 therapy, which they will continue during the trial.

How Is the Trial Designed?

Group I: Phase 2 Combination Treatment Experimental Treatment 2 Interventions

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

Group II: Phase 1 Single Agent Experimental Treatment 1 Intervention

GIM-531 administered orally daily

Who Is Running the Clinical Trial?

Georgiamune Inc

Lead Sponsor

Trials

3

Recruited

310+

Published Research Related to This Trial

Gilteritinib is an effective treatment for adults with relapsed or refractory acute myeloid leukemia (AML) with FLT3 mutations, showing advantages in survival and a generally favorable safety profile.

While gilteritinib is associated with common side effects like diarrhea and nausea, serious gastrointestinal events such as GI hemorrhage and perforation have been reported, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data. Gozzo, L., Nardo, A., Brancati, S., et al.[2023]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

The study found that combining MDM2 inhibitors like Nutlin-3 or RG7388 with cisplatin can enhance the effectiveness of treatment in ovarian cancer cell lines, leading to increased activation of the p53 protein, which is crucial for cell cycle arrest and apoptosis.

This combination therapy showed synergistic effects, meaning it worked better together than separately, particularly in cells with a functional p53 gene, suggesting a promising new approach to overcome resistance to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical efficacy and synergistic potential of the MDM2-p53 antagonists, Nutlin-3 and RG7388, as single agents and in combined treatment with cisplatin in ovarian cancer. Zanjirband, M., Edmondson, RJ., Lunec, J.[2022]

In a first-in-human phase I study involving 51 patients with advanced solid tumors, CGM097 was found to be tolerable with no dose-limiting toxicities, although delayed-onset thrombocytopenia was a common side effect.

The disease control rate was 39%, with one patient achieving a partial response and 19 patients maintaining stable disease, indicating limited but notable antitumor activity and providing insights for optimizing dosing regimens for future HDM2 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies. Bauer, S., Demetri, GD., Halilovic, E., et al.[2023]

In a study of 307 Chinese patients with gastrointestinal stromal tumors (GISTs) receiving imatinib, the plasma trough concentrations (Cmin) were found to be significantly higher than those reported in Western populations, particularly at higher doses (400 mg, 600 mg, and 800 mg).

Higher imatinib Cmin levels were correlated with severe adverse reactions such as periorbital and limb edema, anemia, and rash, indicating that monitoring these concentrations could help manage and mitigate side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlations between imatinib plasma trough concentration and adverse reactions in Chinese patients with gastrointestinal stromal tumors. Xia, Y., Chen, S., Luo, M., et al.[2022]

Imatinib (Gleevec) has shown high efficacy in treating chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST), with over 12,000 patients involved in clinical trials, indicating its effectiveness as a treatment option.

The drug is generally well tolerated, with manageable common side effects such as nausea and rash, and ongoing studies have helped identify rarer toxicities and predictors of common side effects, as well as its impact on male fertility and pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib treatment: specific issues related to safety, fertility, and pregnancy. Hensley, ML., Ford, JM.[2022]

A comprehensive analysis of the FDA Adverse Event Reporting System identified 5226 cases of gastrointestinal perforation (GIP) linked to 37 novel antineoplastic drugs, highlighting a significant safety concern associated with these medications.

Out of the 37 drugs analyzed, 22 showed statistically significant signals for GIP, particularly those targeting vascular endothelial growth factor and immune checkpoints, indicating a need for careful monitoring and management of this adverse event in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal perforation associated with novel antineoplastic agents: A real-world study based on the FDA Adverse Event Reporting System. Yu, Z., Zhu, H., Chen, H., et al.[2023]

Nutlin-3 effectively stabilizes the tumor suppressor p53 in gastric cancer cells with wild-type p53, leading to increased expression of important proteins that promote cell cycle arrest and apoptosis.

In combination with traditional chemotherapy drugs like 5-fluorouracil and cisplatin, nutlin-3 enhances cytotoxic effects against gastric cancer cells, demonstrating its potential as a promising treatment option for patients with wild-type p53.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells. Endo, S., Yamato, K., Hirai, S., et al.[2021]

The small-molecule MDM2 antagonist nutlin-3 preserves the cell-cycle arrest function of the p53 pathway in various tumor-derived cell lines with wild-type p53, indicating potential therapeutic benefits for these tumors.

Cancer cells with amplified mdm2 genes showed heightened sensitivity to nutlin-3, suggesting that targeting the p53-MDM2 interaction could be an effective treatment strategy for many patients with tumors retaining wild-type p53.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Tovar, C., Rosinski, J., Filipovic, Z., et al.[2018]

Restoring wild-type TP53 activity in pancreatic cancer cells (MIA-PaCa-2) enhances their sensitivity to the MDM2 inhibitor nutlin-3a, suggesting a potential therapeutic strategy for targeting TP53 mutations in pancreatic ductal adenocarcinoma (PDAC).

Co-treatment with nutlin-3a and certain chemotherapeutic agents like irinotecan and oxaliplatin showed antagonistic effects, indicating that while nutlin-3a can sensitize cancer cells, it may not always work well in combination with all therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals. Candido, S., Abrams, SL., Steelman, LS., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06425926

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

2. withpower.com withpower.com/trial/phase-2-melanoma-4-2024-62e3b

GIM-531 for Solid Tumors This trial is for adults with advanced solid tumors, including melanoma, that have worsened after standard treatment or who can't tolerate it. They must not ...

3. synapse.patsnap.com synapse.patsnap.com/article/georgiamune-announces-first-patient-dosed-in-phase-1-trial-of-gim-531-for-cancer-treatment

Georgiamune Announces First Patient Dosed in Phase 1 ... GIM-531 is pioneering in its approach as an oral therapy that selectively inhibits T regulatory cells, marking it as a first-in-class treatment ...

4. biospace.com biospace.com/georgiamune-announces-first-patient-dosed-in-a-first-in-class-phase-1-cancer-treatment-trial-of-gim-531

Georgiamune Announces First Patient Dosed in A ... The first patient has been dosed with GIM-531 in a first-in-human, phase 1 clinical trial for the treatment of advanced cancer patients.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9850086/

Effectiveness and safety of anti-PD-1 monotherapy or ... Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and ...

6. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/gim-531-georgiamune-solid-tumor-likelihood-of-approval/

GIM-531 by Georgiamune for Solid Tumor: Likelihood of ... GIM-531 is under clinical development by Georgiamune and currently in Phase II for Solid Tumor. According to GlobalData, Phase II drugs for ...

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/treg-inhibitor-gim-531?pn=1

Clinical Trials Using Treg Inhibitor GIM-531 - NCI Clinical Trials Using Treg Inhibitor GIM-531. Review the clinical trials ... Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors. Status ...

8. clinicaltrialsarena.com clinicaltrialsarena.com/news/georgiamune-advance-second-oncology-trial/

Georgiamune advance second oncology drug to trials with ... The Phase I/II trial of GIM-531 is investigating the candidate in 84 patients with advanced solid tumours, with an additional focus on cold ...