GI-101 Combination Therapies for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: GI Innovation, Inc.
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.
What safety data exists for GI-101 combination therapies for advanced cancer?The provided research does not contain specific safety data for GI-101 combination therapies or its components like Lenvatinib, Pembrolizumab, or Radiotherapy. The studies focus on other treatments such as simtuzumab, regorafenib, ceritinib, and avapritinib, which are not directly related to GI-101. Therefore, no relevant safety data for GI-101 is available in the provided research.123411
What data supports the idea that GI-101 Combination Therapies for Advanced Cancer is an effective treatment?The available research shows that the combination of lenvatinib and pembrolizumab, which is part of the GI-101 Combination Therapies, has shown promising results in treating various types of advanced cancers. For instance, in advanced endometrial cancer, this combination improved response rates and survival compared to chemotherapy. In advanced renal cell carcinoma, the combination of lenvatinib with everolimus showed better outcomes than everolimus alone. Additionally, in advanced urothelial carcinoma, the combination demonstrated antitumor activity and was safe for patients. These findings suggest that GI-101 Combination Therapies can be effective for treating advanced cancers.678913
Do I need to stop taking my current medications to join the trial?The protocol does not specify if you need to stop taking your current medications. However, you cannot be on chronic systemic steroid therapy or immunosuppressive medications within 2 weeks before starting the trial. Also, you must not have had prior systemic anti-cancer therapy within 4 weeks before treatment.
Is the drug combination of GI-101, Lenvatinib, and Pembrolizumab promising for treating advanced cancer?Yes, the combination of Lenvatinib and Pembrolizumab shows promise for treating advanced cancer. It has shown clinical benefits in patients with endometrial carcinoma and has activity against advanced renal cell carcinoma. This suggests it could be a valuable treatment option for advanced cancer.5781012
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
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 not received a live vaccine in the last 4 weeks.
I have active tuberculosis or a history of it.
I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last 2 weeks.
I have active brain metastases or cancer in the lining of my brain.
I have another type of cancer that is currently active.
I have been treated for an autoimmune disease in the last 2 years.
Participant Groups
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.
6Treatment groups
Experimental Treatment
Group I: GI-101A + PembrolizumabExperimental Treatment2 Interventions
Dose escalation: GI-101A, multiple ascending doses
Dose expansion:
Group II: GI-101AExperimental Treatment1 Intervention
Dose escalation: GI-101A, multiple ascending doses
Dose expansion:
Group III: GI-101 + PembrolizumabExperimental Treatment2 Interventions
Dose escalation: GI-101, multiple ascending doses
Dose expansion:
Group IV: GI-101 + Local RadiotherapyExperimental Treatment2 Interventions
Dose optimization:
Dose expansion:
Group V: GI-101 + LenvatinibExperimental Treatment2 Interventions
Dose optimization:
Dose expansion:
Group VI: GI-101Experimental Treatment1 Intervention
Dose escalation: GI-101, multiple ascending doses
Dose expansion:
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Tisch Cancer Institute (TCI), Icahn School of MedicineNew York, NY
Carolina Biooncology InstituteHuntersville, NC
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Who is running the clinical trial?
GI Innovation, Inc.Lead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
An update on the safety and efficacy of regorafenib in the treatment of solid cancers. [2014]Regorafenib is a multi-targeted kinase inhibitor that has been approved recently for the treatment of certain gastrointestinal (GI) cancers. This review examines the scientific evidence on the efficacy and safety of this agent in Phase I to III studies.
Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer. [2022]Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg/d ceritinib dose.
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. [2022]Label="LESSONS LEARNED">The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma.
Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials. [2022]Regorafenib is a novel multikinase inhibitor (MKI) approved for use in the treatment of metastatic colorectal cancer (CRC), treatment-refractory gastrointestinal stromal tumors, and other solid tumor malignancies. However, the adverse events (AEs) associated with regorafenib have not been systematically investigated. Hence, we performed a meta-analysis to identify AEs associated with regorafenib in patients with advanced solid tumors.
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. [2020]Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases. Pembrolizumab, an antibody targeting PD-1, has moderate efficacy in biomarker-unselected endometrial cancer. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced endometrial carcinoma, after establishing the maximum tolerated dose in a phase 1b study.
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]Pembrolizumab, an anti-PD-1 antibody, results in tumour response in around 15% of patients with advanced gastric cancer who have a PD-L1 combined positive score of at least 1. Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased tumour-associated macrophages and increased infiltration of CD8 T cells, resulting in enhanced anti-tumour activity of PD-1 inhibitors in an in-vivo model. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced gastric cancer in a phase 2 study.
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. [2022]Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.
Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) for Lenvatinib plus Everolimus Versus Everolimus Monotherapy in Patients with Advanced Renal Cell Carcinoma. [2022]The lenvatinib (LEN) plus everolimus (EVE) combination demonstrated improved progression-free survival over everolimus alone in a phase 2 trial (Study-205).
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]Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy.
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]The combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.
A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. [2023]Avapritinib was first approved by the FDA in January 2020 and represents the first precision-targeted drug for gastrointestinal stromal tumours. However, there is a lack of large-scale data relating to adverse events (AEs) related to its use. We aimed to explore the avapritinib-related AEs in real-world practice based on the post-marketing data.
Combined use of pembrolizumab and lenvatinib: A review. [2023]The purpose of this article is to review the pharmacology, safety, evidence for current use, and potential futures uses for combination therapy with pembrolizumab and lenvatinib.
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]Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).