GI-101 Combination Therapies for Advanced Cancer

Recruiting at 11 trial locations

Overseen By Recruiting sites have contact information. Please contact the sites directly.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GI Innovation, Inc.

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS metastases, Hepatitis, Tuberculosis, others

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

Compensation: Varies

Number of Visits: Unknown

430 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment called GI-101 against advanced or spreading solid tumors. It examines GI-101 alone and in combination with other treatments such as pembrolizumab (an immunotherapy drug), lenvatinib (a cancer medication), or local radiotherapy to assess their safety and effectiveness. Individuals with advanced cancer who have not responded to other treatments might be suitable candidates for this trial. The researchers aim to determine how these combinations can improve outcomes for those with difficult-to-treat cancers. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering a chance to be among the first to benefit from potential new therapies.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you have not received certain treatments like systemic anti-cancer therapy or immunosuppressive medications within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that GI-101, whether used alone or with pembrolizumab, is generally well-tolerated. In earlier studies, almost all patients experienced some side effects, with fever and temporary increases in liver enzymes being the most common. These side effects were usually manageable.

Pembrolizumab, already approved for other uses, has a well-known safety record. Most side effects, such as tiredness and skin reactions, can be managed.

Lenvatinib, another treatment in the study, is also used for other conditions and has a well-established safety profile. Common side effects include high blood pressure and diarrhea, but these can often be managed with medical care.

Lastly, GI-101A appears similar to GI-101 in terms of safety, showing good tolerance in patients, even those who had previous treatments.

Overall, while side effects are common, they are usually manageable, and these treatments have shown a good safety record so far. Participants should discuss any concerns with their healthcare provider to understand what this might mean for them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new approaches for tackling advanced cancer. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, GI-101 is designed to precisely target cancer cells, potentially reducing side effects. The combination of GI-101 with Pembrolizumab or Lenvatinib might enhance the immune system’s ability to fight cancer or inhibit tumor growth through distinct pathways, offering hope for improved outcomes. Additionally, the innovative use of GI-101A and its combinations represents cutting-edge research into personalized cancer therapies, aimed at optimizing dose and maximizing effectiveness.

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

Research shows that GI-101, one of the treatments in this trial, may help fight cancer by boosting the body's immune system. It can increase immune cell activity, potentially enabling the body to attack tumors more effectively. Animal studies have demonstrated that GI-101 strengthens the body's natural defenses against tumors, particularly by enhancing key immune cells like CD8+ T cells and NK cells.

In this trial, some participants will receive GI-101 combined with pembrolizumab. Early animal research suggests this combination could enhance tumor-fighting effects. Another group will receive GI-101 with lenvatinib, which, when combined with other treatments, has previously improved survival rates in patients with advanced cancer. Pembrolizumab, a well-known cancer treatment, has shown long-term survival benefits in some cancers. These findings offer hope that the combinations tested in this trial could be effective against advanced cancers. ^{3 4 6 7 8}

Who Is on the Research Team?

Nari Yun, PhD

Principal Investigator

GI Innovation

Are You a Good Fit for This Trial?

Adults with various advanced solid tumors who have good organ and marrow function, an ECOG performance status of 0-1, and controlled HIV (if applicable). They must not have had recent cancer treatments or certain infections, active CNS metastases, a second malignancy, liver disease (except liver metastasis), autoimmune diseases requiring treatment in the last 2 years, known drug hypersensitivities, active tuberculosis or immunodeficiency.

Inclusion Criteria

My organs and bone marrow are functioning well.

I am fully active or can carry out light work.

My side effects from previous cancer treatments have mostly gone away.

Exclusion Criteria

I have not had immunotherapies similar to GI-101.

I have or had Hepatitis B, or I currently have Hepatitis C.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation and Expansion

Participants receive GI-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib, or local radiotherapy. This phase includes dose-escalation and expansion cohorts.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GI-101
• Lenvatinib
• Local Radiotherapy
• Pembrolizumab

Trial Overview The trial is testing GI-101/GI-101A alone or combined with pembrolizumab (an immunotherapy), lenvatinib (a targeted therapy), or local radiotherapy. It aims to assess safety and effectiveness across a range of advanced cancers by measuring how well these treatments work together.

How Is the Trial Designed?

Group I: GI-101A + Pembrolizumab Experimental Treatment 2 Interventions

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Group II: GI-101A Experimental Treatment 1 Intervention

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Group III: GI-101 + Pembrolizumab Experimental Treatment 2 Interventions

Dose escalation: GI-101, multiple ascending doses Dose expansion:

Group IV: GI-101 + Local Radiotherapy Experimental Treatment 2 Interventions

Dose optimization: Dose expansion:

Group V: GI-101 + Lenvatinib Experimental Treatment 2 Interventions

Dose optimization: Dose expansion:

Group VI: GI-101 Experimental Treatment 1 Intervention

Dose escalation: GI-101, multiple ascending doses Dose expansion:

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

Combination therapy with pembrolizumab and lenvatinib is effective as a first-line treatment for clear cell renal carcinoma and as a second-line option for recurrent or metastatic endometrial carcinoma, based on data from five completed clinical trials and two ongoing trials.

This non-chemotherapy regimen helps spare patients from prolonged myelosuppression and lowers the risk of infection, making it a safer alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. Eisinger, C., Muluneh, B.[2023]

Patients with advanced renal cell carcinoma treated with the combination of lenvatinib (LEN) and everolimus (EVE) experienced a significant improvement in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST), gaining an average of 3.7 months compared to those receiving EVE alone.

The LEN+EVE combination resulted in a 24% relative gain in Q-TWiST, indicating a clinically important benefit in quality survival time for patients who had previously undergone antiangiogenic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) for Lenvatinib plus Everolimus Versus Everolimus Monotherapy in Patients with Advanced Renal Cell Carcinoma. Lee, CH., Wan, Y., Smith, A., et al.[2022]

The combination of pembrolizumab and lenvatinib has shown promising efficacy in treating advanced endometrial cancer, with previous trials indicating improved objective response rates and survival outcomes compared to standard chemotherapy.

This ongoing phase 3 trial aims to determine if pembrolizumab plus lenvatinib is superior to the chemotherapy regimen of paclitaxel plus carboplatin in newly diagnosed patients, with a target enrollment of about 875 participants and results expected in 2022.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Marth, C., Tarnawski, R., Tyulyandina, A., et al.[2022]

In a phase 3 trial with 1069 patients, the combination of lenvatinib and pembrolizumab significantly improved progression-free survival compared to sunitinib, with a median of 23.9 months versus 9.2 months, indicating a strong efficacy of this regimen.

Lenvatinib plus pembrolizumab also resulted in longer overall survival compared to sunitinib, while the combination of lenvatinib and everolimus did not show a survival advantage over sunitinib. However, both lenvatinib combinations had a high incidence of grade 3 or higher adverse events, similar to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. Motzer, R., Alekseev, B., Rha, SY., et al.[2022]

In a phase 2 study involving 54 patients with advanced endometrial cancer, the combination of lenvatinib and pembrolizumab resulted in a 39.6% objective response rate at week 24, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with serious adverse events occurring in 30% of patients, including one treatment-related death; however, the safety profile was consistent with previous studies of the individual drugs, except for a higher incidence of hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Makker, V., Rasco, D., Vogelzang, NJ., et al.[2020]

In a phase 2 trial involving 29 patients with advanced gastric cancer, the combination of lenvatinib and pembrolizumab resulted in a promising objective response rate of 69%, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with the most common grade 3 adverse events being manageable, such as hypertension and proteinuria, and no serious treatment-related complications or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Kawazoe, A., Fukuoka, S., Nakamura, Y., et al.[2020]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

Citations

1. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A751

718 Preliminary results of GII-101-P101 (Keynote-B59): GI ... Systemic exposure to GI-101 increased with dose-escalation with half-life of 7.5~10.1 hours, resulting in a dose-dependent increase in NK and ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e14526

Clinical outcomes of GIC-102 monotherapy (GIC-102101) ... The in-vivo study of GIC-102 in combination with GI-101 showed significantly enhanced anti-tumor activity and in-vivo NK cell proliferation ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)59435-2/fulltext

GI101, a novel triple-targeting bispecific CD80-IgG4 ... GI101 elicits improved restoration of immune functions compared to a CD80-Fc in in vitro settings using human PBMCs co-cultured with PD-L1 hi tumor cells.

4. withpower.com withpower.com/trial/phase-2-carcinoma-6-2021-9cbf6

GI-101 Combination Therapies for Advanced Cancer In a phase 3 trial with 1069 patients, the combination of lenvatinib and pembrolizumab significantly improved progression-free survival compared to sunitinib, ...

5. synapse.patsnap.com synapse.patsnap.com/drug/daae82c0399a4499934a29ce2e19e094

SIM-323 - Drug Targets, Indications, Patents A Phase 1/2, Open-label, Dose-escalation, and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03003-X/fulltext

1027P An open-label, multicenter, phase I/II study of GI- ... Treatment-emergent adverse events (TEAEs) occurred in 55 pts (96%); the most common (>30%) were pyrexia (67%) and transient AST increase (37%). Objective ...

7. jitc.bmj.com jitc.bmj.com/content/jitc/10/Suppl_2/A751.full.pdf

GI-101 (CD80-IgG4 Fc-IL2v) as a single agent and in ... Background GI-101 is a novel bispecific fusion protein con- taining CD80 and interleukin-2 variant, designed to boost immune cell proliferation including ...

8. simcere.com simcere.com/en/news/detail.aspx?mtt=66

Simcere and GI Innovation Announce Collaboration ... Preclinical data shows that GI-101 treatment produces higher numbers of tumor-infiltrating lymphocytes which translates into more potent anti- ...