GI-102 for Advanced Cancer

Recruiting at 9 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: GI Innovation, Inc.

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: CNS metastases, Active infections, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing GI-102, a new protein treatment, in patients with advanced or spreading tumors. The treatment aims to help the immune system fight cancer by boosting certain immune cells while avoiding those that suppress the response.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic anti-cancer therapy, you must stop it at least 4 weeks before starting the trial. If you are on chronic systemic steroid therapy or immunosuppressive medications, you must stop them 2 weeks before the trial begins.

What data supports the effectiveness of the treatment GI-102 for Advanced Cancer?

Research shows that combining interleukin-2 (IL-2) with CD80 can improve immune responses against tumors, as seen in gastric cancer studies. Additionally, IL-2 has shown effectiveness in treating other cancers like melanoma and renal cell carcinoma, suggesting potential benefits for advanced cancer patients. ^{1 2 3 4 5}

Is GI-102 safe for humans?

GI-102, also known as IL-2, has been used in cancer treatment but can cause serious side effects, including life-threatening gastrointestinal issues and cardiovascular problems. These side effects are more common with high doses, and patients may need intensive care support during treatment. ^{2 6 7 8 9}

What makes the drug GI-102 unique for treating advanced cancer?

GI-102 is unique because it combines CD80, which helps the immune system recognize cancer cells, with a modified version of interleukin-2 (IL-2), which boosts immune cell activity, potentially enhancing the body's ability to fight cancer more effectively than using either component alone. ^{2 3 10 11 12}

Research Team

Nari Yun, PhD

Principal Investigator

GI Innovation, Inc.

Eligibility Criteria

Adults with advanced solid tumors who have good organ and bone marrow function, measurable disease, a performance status indicating they can care for themselves (ECOG 0-1), and no severe recent side effects from past cancer treatments. HIV+ patients must be on effective ART. Not eligible if they have active brain metastases, another cancer, hepatitis B or C infections, tuberculosis, uncontrolled infections, recent immunotherapies like GI-102's action mode or any cancer treatment within the last month.

Inclusion Criteria

I am fully active or can carry out light work.

I am 18 years or older, or 19 where required by local laws.

My organs and bone marrow are working well.

Exclusion Criteria

I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last 2 weeks.

I have a history of liver disease but not due to cancer spread.

My cancer has spread to my brain or the membranes around my brain.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Optimization

Dose escalation and optimization phase of GI-102 intravenous (IV) monotherapy, including dose optimization cohorts in patients with 2L+, CPI-refractory metastatic melanoma

3 weeks

Multiple visits for dose escalation and monitoring

Dose Escalation and Expansion

Dose escalation and expansion phase of GI-102 subcutaneous (SC) monotherapy

24 months

Regular visits for treatment and monitoring

Combination Treatment

Indication specific cohorts of GI-102 IV in combination with conventional anti-cancer drugs or trastuzumab deruxtecan (T-DXd) and pembrolizumab

24 months

Regular visits for combination treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GI-102 (Other)

Trial Overview The trial is testing GI-102 as a single agent to see how safe it is and how well it works against different types of advanced or spreading solid tumors. It will look at how the body processes the drug and its effectiveness in shrinking or controlling tumor growth.

Participant Groups

Group I: GI-102 subcutaneous (SC) Experimental Treatment 1 Intervention

Dose escalation: GI-102 subcutaneous (SC), multiple ascending doses Dose expansion: GI-102 subcutaneous (SC), sRP2D

Group II: GI-102 + trastuzumab deruxtecan (T-DXd) Experimental Treatment 2 Interventions

Group III: GI-102 + pembrolizumab Experimental Treatment 2 Interventions

Group IV: GI-102 + paclitaxel + bevacizumab Experimental Treatment 3 Interventions

Group V: GI-102 + eribulin Experimental Treatment 2 Interventions

Group VI: GI-102 + doxorubicin Experimental Treatment 2 Interventions

Group VII: GI-102 Experimental Treatment 1 Intervention

Dose escalation: GI-102 intravenous (IV), multiple ascending doses Dose optimization: GI-102 intravenous (IV), sRP2D Dose optimization: GI-102 intravenous (IV), sRP2D-1 (or sRP2D+1)

Who Is Running the Clinical Trial?

GI Innovation, Inc.

Lead Sponsor

Trials

2

Recruited

790+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The monoclonal antibody 105AD7, designed to mimic a colorectal tumor antigen, was found to be nontoxic in a Phase I trial and associated with prolonged survival in advanced colorectal cancer patients compared to a contemporary control group.

Immunization with 105AD7 stimulated significant anti-tumor immune responses, including increased activity of CD4 and natural killer (NK) cells at the tumor site, suggesting that this therapy may enhance the body's ability to fight colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evidence that the human monoclonal anti-idiotypic antibody 105AD7, delays tumor growth by stimulating anti-tumor T-cell responses. Buckley, DT., Robins, AR., Durrant, LG.[2006]

Recombinant human IL-2 (rIL-2) is being studied for its potential benefits in HIV-infected patients, although it is already approved for treating metastatic melanoma and renal cell carcinoma, where it shows durable responses.

The treatment with rIL-2 is associated with significant toxicity, which limits its use to healthier patients; however, there is ongoing research to engineer a safer IL-2 variant that could separate efficacy from toxicity, potentially improving its therapeutic index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic enhancement of IL-2 through molecular design. Cassell, DJ., Choudhri, S., Humphrey, R., et al.[2019]

Combining CD80 gene therapy with interleukin-2 significantly enhances the immune response against gastric cancer, leading to increased cytotoxicity of mononuclear cells compared to other treatments.

In an animal model, the combination therapy resulted in the longest median survival of 46 days for those with intraperitoneal tumors, indicating a promising approach for improving outcomes in gastric cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A synergistic antitumor effect of interleukin-2 addition with CD80 immunogene therapy for peritoneal metastasis of gastric carcinoma. Kosaka, K., Yashiro, M., Sakate, Y., et al.[2018]

A short-term pre-operative treatment with interleukin-2 (IL-2) significantly reduced the progression rate of colorectal cancer in patients undergoing radical surgery, with a 21.4% progression rate in the IL-2 group compared to 43.1% in the control group after a median follow-up of 54 months.

The positive effects of IL-2 immunotherapy were observed in both Dukes' stage B and C patients, suggesting that early activation of the immune system can help counteract cancer growth and improve patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-operative immunoprophylaxis with interleukin-2 may improve prognosis in radical surgery for colorectal cancer stage B-C. Brivio, F., Fumagalli, L., Lissoni, P., et al.[2022]

In a study of 64 patients with metastatic melanoma (MMEL) and metastatic renal cell carcinoma (MRCC) undergoing IL-2 therapy, changes in T cell subsets were observed, indicating a potential correlation between immune profile alterations and treatment outcomes.

IL-2 therapy caused a temporary decrease in circulating effector lymphocytes and an increase in regulatory T cells, with specific changes in CD8 T cell subsets depending on the cancer type, suggesting that monitoring these immune changes could help predict patient responses to IL-2 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome. Foureau, DM., Amin, A., White, RL., et al.[2014]

In a study involving 42 cancer patients treated with interleukin-2 (IL-2), serious gastrointestinal complications occurred in 3 patients, including life-threatening conditions like sigmoid colon perforation and ischemic necrosis.

Despite the common expectation of only minor side effects, the findings suggest that major gastrointestinal issues with IL-2 therapy may be more frequent than previously thought, highlighting the need for increased awareness and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unusual gastrointestinal complications of interleukin-2 therapy. Rahman, R., Bernstein, Z., Vaickus, L., et al.[2019]

In a study of 1535 patients receiving high-dose interleukin-2 (IL-2) therapy, those who experienced immune-related adverse events (irAEs) had significantly better tumor control (71% vs. 56%) and overall survival, particularly in metastatic melanoma (median 48 months vs. 18 months) and metastatic renal cell cancer (median 60 months vs. 40 months).

The majority of irAEs were related to IL-2 therapy, primarily manifesting as vitiligo and thyroid dysfunction, indicating that while these adverse events are concerning, they may also signal a beneficial immune response that enhances treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIMSM registry. Curti, B., Daniels, GA., McDermott, DF., et al.[2018]

High-dose recombinant human IL-2 (rhIL-2) has shown potential as a treatment for metastatic melanoma and renal cell carcinoma, leading to durable antitumor responses in some patients, but its use is limited due to severe side effects that require specialized medical support.

Recent advancements in drug development, including engineered IL-2 variants, aim to enhance the efficacy and safety of IL-2 therapies by selectively activating anti-tumor immune cells, potentially expanding its use beyond current FDA-approved indications and allowing for safer combinations with other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking Oncologic Treatment Strategies with Interleukin-2. Ko, B., Takebe, N., Andrews, O., et al.[2023]

Recombinant interleukin-2 (rIL-2) has shown effectiveness in inducing remissions in metastatic renal cell cancer and malignant melanoma, with high-dose intravenous rIL-2 approved in the US for these conditions, although it comes with significant toxicity.

Alternative dosing regimens, such as low-dose and continuous infusion, have similar response rates with less toxicity, and combination therapies with rIL-2 and other agents like IFNalpha have improved response rates, though they do not always lead to better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-2 in cancer therapy: uses and optimum management of adverse effects. Mekhail, T., Wood, L., Bukowski, R.[2018]

ALT-803, a novel IL-15 superagonist, demonstrated significantly stronger effects on natural killer (NK) and T cells compared to IL-15, effectively eliminating myeloma cells in tumor-bearing mice and prolonging their survival.

The treatment with ALT-803 activated CD8(+) memory T cells to produce large amounts of IFN-γ and showed nonspecific cytotoxicity against various tumor cells, indicating its potential as an effective immunotherapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma. Xu, W., Jones, M., Liu, B., et al.[2021]

In a murine model of cancer, combining anti-CD3 monoclonal antibodies with interleukin-2 (IL-2) significantly enhanced T-cell responsiveness and induced tumor regression, leading to longer survival times compared to using either treatment alone.

This combination therapy resulted in increased expression of key cytotoxic molecules, suggesting a more effective antitumor strategy that could improve current immunotherapy approaches for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with anti-CD3 monoclonal antibodies and recombinant interleukin 2: stimulation of molecular programs of cytotoxic killer cells and induction of tumor regression. Nakajima, F., Khanna, A., Xu, G., et al.[2019]

In patients with advanced colorectal cancer, those who responded to recombinant interleukin 2 (rIL-2) therapy had significantly lower levels of pretreatment serum IL-6 and soluble IL-2 receptor (sIL-2R) compared to non-responders, suggesting these markers could help identify likely responders.

During rIL-2 treatment, responders showed increased levels of IL-6 and low levels of prostaglandin E2 (PGE2), while non-responders did not produce IL-6 and had elevated PGE2 levels, indicating that the balance of these cytokines and prostaglandins plays a crucial role in the efficacy of rIL-2 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses. Deehan, DJ., Heys, SD., Simpson, WG., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical evidence that the human monoclonal anti-idiotypic antibody 105AD7, delays tumor growth by stimulating anti-tumor T-cell responses. [2006]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Therapeutic enhancement of IL-2 through molecular design. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

A synergistic antitumor effect of interleukin-2 addition with CD80 immunogene therapy for peritoneal metastasis of gastric carcinoma. [2018]

4. Greece pubmed.ncbi.nlm.nih.gov

Pre-operative immunoprophylaxis with interleukin-2 may improve prognosis in radical surgery for colorectal cancer stage B-C. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Unusual gastrointestinal complications of interleukin-2 therapy. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the PROCLAIMSM registry. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Rethinking Oncologic Treatment Strategies with Interleukin-2. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Interleukin-2 in cancer therapy: uses and optimum management of adverse effects. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy with anti-CD3 monoclonal antibodies and recombinant interleukin 2: stimulation of molecular programs of cytotoxic killer cells and induction of tumor regression. [2019]

12. England pubmed.ncbi.nlm.nih.gov

In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses. [2019]