GI-101 Combination Therapies for Advanced Cancer

Recruiting at6 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: GI Innovation, Inc.

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS metastases, Hepatitis, Tuberculosis, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy (RT) over a range of advanced and/or metastatic solid tumors.

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.

What data supports the effectiveness of the drug combination of lenvatinib and pembrolizumab for advanced cancer?

Research shows that the combination of lenvatinib and pembrolizumab has demonstrated promising results in treating various advanced cancers, including renal cell carcinoma, urothelial carcinoma, endometrial cancer, and gastric cancer. These studies indicate improved survival rates and tumor response compared to other treatments. ^{1 2 3 4 5}

What makes the GI-101 combination therapy unique for advanced cancer?

The GI-101 combination therapy is unique because it combines lenvatinib, a multikinase inhibitor, with pembrolizumab, an immune checkpoint inhibitor, which together have shown clinical benefits in other cancers like endometrial carcinoma. This combination targets both cancer cell growth and the immune system, potentially offering a novel approach for advanced cancer treatment. ^{1 2 6 7 8}

Research Team

Nari Yun, PhD

Principal Investigator

GI Innovation

Eligibility Criteria

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.

I am 18 years or older, or meet the age requirement in my area.

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.

Trial Timeline

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

Treatment Details

Interventions

• GI-101 (Virus Therapy)
• Lenvatinib (Tyrosine Kinase Inhibitor)
• Local Radiotherapy (Radiation)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

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

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. [2022]

2. Netherlands 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. [2022]

3. Switzerland 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. [2023]

4. England 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. [2022]

5. England 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. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

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

Combined use of pembrolizumab and lenvatinib: A review. [2023]

8. England 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. [2020]