GS-1811 + Zimberelimab for Solid Tumors
Recruiting in Palo Alto (17 mi)
+26 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Gilead Sciences
Must not be taking: Immunotherapy, Chemotherapy
Disqualifiers: Active infection, Autoimmune disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called GS-1811 alone and with zimberelimab in patients with advanced solid tumors who have no other treatment options. The study aims to find the safest and most effective dose.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot have any concurrent anticancer treatment and must stop any anticancer therapy within a specified time before starting the study: immunotherapy or biologic therapy within 28 days, chemotherapy within 21 days, targeted small molecule therapy within 14 days, hormonal or other adjunctive therapy within 14 days, and radiotherapy within 21 days.
What data supports the idea that GS-1811 + Zimberelimab for Solid Tumors is an effective treatment?
The available research does not provide specific data on the effectiveness of GS-1811 + Zimberelimab for Solid Tumors. Instead, it focuses on other treatments like nivolumab and pembrolizumab for advanced non-small cell lung cancer (NSCLC). These treatments have shown improved survival rates and disease control in patients with NSCLC. For example, nivolumab has demonstrated better survival compared to traditional chemotherapy in previously treated NSCLC patients. However, there is no direct evidence in the provided research about the effectiveness of GS-1811 + Zimberelimab for Solid Tumors.
12345What safety data is available for GS-1811 + Zimberelimab treatment?
Zimberelimab, also known as GLS-010, has been evaluated for safety in a phase II study for relapsed or refractory classical Hodgkin lymphoma, showing promising safety results. It has been approved in China for this condition. Additionally, similar PD-1 inhibitors like nivolumab have been studied extensively, with common adverse effects including fatigue, rash, and diarrhea, and serious adverse effects like hypophosphatemia and lymphopenia being less common. This suggests a potential safety profile for Zimberelimab in line with other PD-1 inhibitors.
678910Eligibility Criteria
Adults with advanced solid tumors who've tried all other treatments without success or can't tolerate them are eligible. They must have measurable disease, be in fair to good physical condition (ECOG 0-2), and agree to use contraception. Tissue samples for testing are required.Inclusion Criteria
I have an advanced solid tumor and cannot take or have tried all known beneficial treatments.
My organs are working well.
I agree to use birth control if I can have children and am sexually active.
+7 more
Exclusion Criteria
I had a severe allergic reaction to previous immunotherapy.
I have not received any live vaccines in the last 30 days.
I have no active cancer except for certain skin, prostate, or bladder cancers, or have been cancer-free for over 2 years.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Denikitug as monotherapy or in combination with Zimberelimab to evaluate safety, tolerability, and determine the maximum tolerated dose
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is assessing GS-1811 alone or combined with Zimberelimab to find the safest and most effective doses for treating advanced solid tumors. It's divided into parts: some test GS-1811 solo, others in combination therapy.
6Treatment groups
Experimental Treatment
Group I: Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and ScheduleExperimental Treatment2 Interventions
Group II: Part E: Denikitug Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Group III: Part D: Denikitug + Zimberelimab Dose ExpansionExperimental Treatment2 Interventions
Group IV: Part C: Denikitug + Zimberelimab Dose EscalationExperimental Treatment2 Interventions
Group V: Part B - Mandatory Paired Tumor BiopsyExperimental Treatment1 Intervention
Group VI: Part A - Denikitug Dose EscalationExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Smilow Cancer Center, Yale University School of MedicineNew Haven, CT
University Health Network, Princess Margaret Cancer CentreToronto, Canada
University of Texas Southwestern Medical CenterDallas, TX
WCG IRBLa Jolla, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Gilead SciencesLead Sponsor
References
Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. [2022]In this first-in-human phase I study (NCT02132754), we explored MK-4166 [humanized IgG1 agonist mAb targeting glucocorticoid-induced TNF receptor (GITR)] with and without pembrolizumab in advanced solid tumors.
Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. [2022]Nivolumab improves disease control and survival in advanced NSCLC in patients with good performance status (PS), but there is limited data on its efficacy in patients with poor PS.
Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. [2022]Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial.
Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.
Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. [2023]Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non-small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combination with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with checkpoint inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC.
Zimberelimab: First Approval. [2022]Zimberelimab (®) is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody being developed by Gloria Biosciences, Arcus Biosciences and Taiho Pharmaceutical Co. for the treatment of various cancers including cervical cancer, non-small cell lung cancer and classical Hodgkin's lymphoma. Based on the results of a phase II trial, zimberelimab was recently approved for marketing in China as treatment for relapsed or refractory classical Hodgkin's lymphoma. This article summarizes the milestones in the development of zimberelimab leading to this first approval.
Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study. [2022]GLS-010 (zimberelimab) is a novel, fully human, anti-programmed death-1 monoclonal antibody that shows promising efficacy and safety in advanced solid tumors. This trial aimed to evaluate the efficacy and safety of GLS-010 (zimberelimab) in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r-cHL).
Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]Immune checkpoint inhibition therapy has benefited people and shown powerful anti-tumor activity during the past several years. Nivolumab, a fully human IgG4 monoclonal antibody against PD-1, is a widely studied immune checkpoint inhibitor for the treatment of cancers. To assess the safety and efficacy of nivolumab, 27 clinical trials on nivolumab were analyzed. Results showed that the summary risks of all grade adverse effects (AEs) and grade ≥3 AEs were 0.65 and 0.12. The rate of nivolumab-related death was 0.25%. The most common any grade AEs were fatigue (25.1%), rush (13.0%), pruritus (12.5%), diarrhea (12.1%), nausea (11.8%) and asthenia (10.4%). The most common grade ≥3 AEs were hypophosphatemia (only 2.3%) and lymphopenia (only 2.1%). The pooled objective response rate (ORR), 6-month progression-free survival (PFS) rate and 1-year overall survival (OS) rate were 0.26, 0.40 and 0.52, respectively. The odds ratio of ORR between PD-L1 positive and negative was 2.34 (95% CI 1.77-3.10, p
Prognostic Impact of Immune-related Adverse Events in Gastric Cancer Patients Treated With Nivolumab. [2022]To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC).
A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. [2018]This phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of demcizumab (OMP-21M18), a humanized IgG2 mAb targeting the Notch ligand DLL4 in adult patients with advanced malignancies.
Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. [2022]Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma.
Persistence of denosumab in Slovak patients with bone metastases - a prospective observational study. [2023]An integrated analysis of phase III trials in patients with advanced solid tumors demonstrated superiority of denosumab over zoledronic acid in preventing skeletal-related events. A drug's clinical efficacy, however, depends on regular and continued administration (persistence); persistence in Slovak real-life is yet undetermined for denosumab in the oncology indication.
Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. [2022]This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma.
Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy. [2022]Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1 or CD279) have noticeably improved the treatment landscape of advanced cancer patients. Nivolumab, the most well-known genetically engineered anti-PD-1 monoclonal antibody (mAb), promotes anti-tumor immunity and shows excellent capability for treating various cancers, particularly lung cancer, renal cancer, and melanoma. Systemic administration of nivolumab could inspire durable therapeutic responses not typically seen with traditional cytotoxic anti-cancer agents. However, nivolumab monotherapy is ineffective in 60-70 percent of patients. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and multifactorial. Recently, the rationality of adding other conventional therapies such as chemo-radiotherapy and targeted therapies such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and VEGF/VEGFR inhibitors to nivolumab has strongly been verified. These regimens overcome cancer resistance and thus boost nivolumab efficacy in cancer patients. Herein, we discuss the current status of the combination therapy with nivolumab in cancer patients, with a particular focus on the recent clinical reports.