GI-102 for Advanced Cancer

Recruiting at 14 trial locations

Overseen By Jay Kim

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GI Innovation, Inc.

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: CNS metastases, Active infections, others

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

Compensation: Varies

Number of Visits: Unknown

358 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GI-102 (also known as CD80-IL2v3) to evaluate its safety and effectiveness for individuals with advanced or spreading solid tumors (cancers that form solid lumps). Researchers are examining GI-102 alone and in combination with other cancer drugs like pembrolizumab and trastuzumab deruxtecan. Individuals with advanced cancer who have already tried other treatments might be suitable candidates for this study. The goal is to determine how well GI-102 works and how the body processes it. As a Phase 1 trial, this study focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

A previous study found that GI-102 was generally well tolerated when administered through an IV, with doses up to 0.45 mg/kg every three weeks showing good results. Most participants did not experience severe side effects at these levels. The study focused on patients with advanced solid tumors and demonstrated some positive effects against the cancer.

For the under-the-skin form of GI-102, early results suggest it might work better than the IV form based on initial research. However, detailed safety information for this method is still being gathered.

When combined with other cancer drugs like paclitaxel, bevacizumab, trastuzumab deruxtecan, pembrolizumab, eribulin, or doxorubicin, each combination may have different safety considerations. For example, bevacizumab has a well-known safety record, and trastuzumab deruxtecan is effective for certain cancer types, though it has specific side effects that can be managed.

Overall, since GI-102 is still in early testing, its full safety profile remains unknown. Participants in these trials help researchers learn about the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GI-102 because it offers a fresh approach to treating advanced cancer by being tested in combination with various other cancer drugs. Unlike traditional treatments that often focus on a single mechanism, GI-102 is being explored for its versatility when combined with paclitaxel, bevacizumab, trastuzumab deruxtecan, pembrolizumab, eribulin, and doxorubicin. This combination strategy aims to enhance the effectiveness of each regimen by potentially improving how cancer cells are targeted and destroyed. Additionally, GI-102 is being tested in both intravenous and subcutaneous forms, offering different delivery methods that could improve patient convenience and treatment tolerance. This multi-pronged approach has the potential to provide better outcomes for patients who have exhausted other treatment options.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that GI-102 could be a promising treatment for advanced cancers. GI-102 is a special protein designed to boost the immune system's ability to fight tumors. In early studies with patients who have advanced solid tumors, GI-102 showed initial success in slowing tumor growth. In this trial, participants may receive GI-102 alone or with other cancer drugs like paclitaxel and bevacizumab, which may further help the body combat cancer. Tests in mice also showed a significant reduction in tumor size. These results suggest that GI-102 could be an effective option for treating advanced cancers. ^{2 5 6 7 8}

Who Is on the Research Team?

Nari Yun, PhD

Principal Investigator

GI Innovation, Inc.

Are You a Good Fit for This Trial?

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.

My organs and bone marrow are working well.

Measurable disease as per RECIST v1.1

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 active tuberculosis or a history of it.

Known hypersensitivity to any of the components of the drug products and/or excipients of GI-102

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• GI-102

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05824975

NCT05824975 | A Study to Evaluate the Safety and ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent and in combination ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT460384

A first-in-human, phase 1/2a study of GI-102 (CD80-IL2v3) ... Here we report preliminary safety and efficacy data of GI-102 from a phase 1/2a trial in patients with metastatic solid tumors. Methods: NCT05824975 is an ...

3. withpower.com withpower.com/trial/phase-2-neoplasms-3-2023-857e5

GI-102 for Advanced Cancer 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 ...

4. researchgate.net researchgate.net/publication/381412954_A_first-in-human_phase_12a_study_of_GI-102_CD80-IL2v3_in_patients_with_advanced_or_metastatic_solid_tumors_Initial_results_from_dose_escalation

A first-in-human, phase 1/2a study of GI-102 (CD80-IL2v3 ... GI-102 was administered intravenously every 3 weeks until disease progression or unacceptable toxicities. Disease was assessed every 6 weeks using RECIST v1.1.

5. mskcc.org mskcc.org/cancer-care/clinical-trials/24-094

A Phase 1a/2 Study of GI-102 Immunotherapy in People ... The people in this study have sarcoma that has spread. GI-102 works by boosting the power of your immune system to find and kill cancer cells. It takes the ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2598

A first-in-human, phase 1/2a study of GI-102 (CD80-IL2v3) ... Here we report preliminary safety and efficacy data of GI-102 from a phase 1/2a trial in patients with metastatic solid tumors. Methods: ...

7. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A824

729 A first-in-human, open-label, multicenter, phase 1/2a, ... GI-102 (CD80-IL2v3) is a novel immunocytokine, designed to direct IL-2v to tumor and immune cells. IL-2v3 of GI-102 is designed to abolish the affinity to IL-2 ...

8. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.2598

A first-in-human, phase 1/2a study of GI-102 (CD80-IL2v3) ... Here we report preliminary safety and efficacy data of GI-102 from a phase 1/2a trial in patients with metastatic solid tumors. Methods: NCT05824975 is an ...