GS-1811 + Zimberelimab for Solid Tumors

Recruiting at 29 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Active infection, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

416 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and optimal dose of a new treatment, denikitug (GS-1811), both alone and with zimberelimab, for individuals with advanced solid tumors. The researchers aim to evaluate the effectiveness of these treatments, both individually and in combination, against tumors unresponsive to other therapies. Individuals with advanced solid tumors who have not found success with available treatments may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new therapy.

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.

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

Research shows that the safety of denikitug (GS-1811) remains under investigation. This marks the first human trial of denikitug, as scientists work to determine its safety and optimal dosage. Due to the early stage of testing, safety information is limited.

For zimberelimab, more data is available. Studies have shown that zimberelimab is generally well-tolerated. Some participants experienced side effects, but these were usually manageable. These studies suggest it may be safe for most people, though individual reactions can vary.

In this trial, denikitug is tested both alone and with zimberelimab. The researchers aim to assess the safety of using these drugs together and to find the right dose. Until more results are available, participants are closely monitored to manage any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GS-1811 and Zimberelimab for solid tumors because they offer a novel approach compared to the existing treatments. Unlike traditional therapies that often target the tumor itself, GS-1811 is designed to enhance the body's immune response specifically by targeting key immune pathways. Zimberelimab, on the other hand, is a type of immunotherapy known as a checkpoint inhibitor, which helps the immune system recognize and attack cancer cells more effectively. This combination has the potential to improve outcomes by leveraging the body's natural defenses, offering a new avenue of hope for patients with solid tumors.

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

Research has shown that GS-1811 (denikitug) has promising effects against tumors in early studies using mice. It targets CCR8, a protein on certain immune cells, leading to a significant reduction in tumors in these studies. However, researchers are still studying GS-1811's effectiveness in humans, and there is no specific information yet about its use for solid tumors.

In this trial, some participants will receive GS-1811 alone, while others will receive it with zimberelimab. Zimberelimab helps the immune system fight cancer cells. While research is ongoing, it is important to note that this combination is still being tested for effectiveness against solid tumors. ^{1 2 4 5 6}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• GS-1811
• Pembrolizumab
• Zimberelimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule Experimental Treatment 2 Interventions

Group II: Part E: Denikitug Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Group III: Part D: Denikitug + Zimberelimab Dose Expansion Experimental Treatment 2 Interventions

Group IV: Part C: Denikitug + Zimberelimab Dose Escalation Experimental Treatment 2 Interventions

Group V: Part B - Mandatory Paired Tumor Biopsy Experimental Treatment 1 Intervention

Group VI: Part A - Denikitug Dose Escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

Denosumab was found to be noninferior to zoledronic acid in delaying skeletal-related events (SRE) in patients with advanced cancer and bone metastases, indicating it is an effective alternative treatment option.

Denosumab offers advantages such as subcutaneous administration and does not require renal monitoring, while it was associated with a higher incidence of hypocalcemia compared to zoledronic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Henry, DH., Costa, L., Goldwasser, F., et al.[2022]

In a study of 66 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab, those with a poor performance status (PS ≥2) had a significantly shorter median overall survival of 3.04 months compared to 10.23 months for those with better performance status (PS ≤1).

Despite similar rates of treatment-related adverse events between the two groups, the findings suggest that performance status is a crucial factor in predicting survival outcomes and should be considered when selecting immunotherapy treatments for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. Abbas, MN., Klevansky, M., Koczwara, B., et al.[2022]

In a phase II trial involving 85 Chinese patients with relapsed or refractory classical Hodgkin lymphoma, GLS-010 (zimberelimab) demonstrated a high objective response rate of 90.6%, with a complete response rate of 32.9% over a median follow-up of 15.8 months.

While GLS-010 showed promising efficacy, it also had a high incidence of treatment-related adverse events (92.9%), with 28.2% of participants experiencing severe (Grade III or IV) side effects, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study. Lin, N., Zhang, M., Bai, H., et al.[2022]

Demcizumab, a humanized monoclonal antibody targeting the Notch ligand DLL4, was generally well tolerated in a phase I trial with 55 patients, showing disease stabilization and some tumor size reduction at doses up to 5 mg weekly.

The most common treatment-related adverse event was hypertension (47%), and prolonged use at higher doses raised concerns about congestive heart failure, indicating the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Smith, DC., Eisenberg, PD., Manikhas, G., et al.[2018]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

A phase I/II trial involving 46 patients with untreated advanced non-small cell lung cancer (NSCLC) demonstrated that the combination of carboplatin, nab-paclitaxel, and pembrolizumab is a safe and effective treatment, achieving a median overall survival of 15.4 months.

The study found a 35% overall response rate and a median progression-free survival of 5.6 months, indicating that this regimen can provide a durable benefit for patients, regardless of their PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Gentzler, RD., Mohindra, NA., Jalal, SI., et al.[2023]

In a study of 110 patients with unresectable advanced gastric cancer receiving nivolumab monotherapy, those who developed immune-related adverse events (irAEs) had significantly better progression-free and overall survival compared to those who did not experience irAEs.

Patients who continued nivolumab treatment despite experiencing irAEs showed improved overall survival compared to those who discontinued treatment, suggesting that managing irAEs effectively can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Impact of Immune-related Adverse Events in Gastric Cancer Patients Treated With Nivolumab. Suematsu, H., Kano, K., Yamada, T., et al.[2022]

In a study of 54 Slovak patients with bone metastases, 84.8% maintained regular administration of denosumab over 24 weeks, indicating good persistence in real-world clinical practice.

No cases of osteonecrosis of the jaw were reported, and the incidence of adverse drug reactions was consistent with previous studies, suggesting that denosumab is a safe option for preventing skeletal-related events in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of denosumab in Slovak patients with bone metastases - a prospective observational study. Porubská, M., Němcová, A.[2023]

Nivolumab, an anti-PD-1 monoclonal antibody, has significantly improved treatment outcomes for advanced cancers like lung cancer, renal cancer, and melanoma, promoting long-lasting anti-tumor immunity.

Despite its effectiveness, nivolumab monotherapy fails in 60-70% of patients, but combining it with other therapies, such as chemotherapy or CTLA-4 inhibitors, has been shown to enhance its efficacy and overcome resistance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy. Abedi Kiasari, B., Abbasi, A., Ghasemi Darestani, N., et al.[2022]

In a phase 3 trial involving 811 patients with lung cancer, denosumab improved median overall survival (8.9 months) compared to zoledronic acid (7.7 months), indicating its potential as a more effective treatment for bone metastases.

Denosumab showed a lower incidence of serious adverse events (66.0%) compared to zoledronic acid (72.9%), and the rates of osteonecrosis of the jaw were similar between the two treatments, suggesting a favorable safety profile for denosumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Scagliotti, GV., Hirsh, V., Siena, S., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

Zimberelimab is an anti-PD-1 monoclonal antibody that has been approved in China for treating relapsed or refractory classical Hodgkin's lymphoma based on a successful phase II trial.

The drug is being developed for various cancers, including cervical cancer and non-small cell lung cancer, highlighting its potential broad application in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zimberelimab: First Approval. Markham, A.[2022]

In a phase I study involving 113 patients with advanced solid tumors, MK-4166 was found to be tolerable, with only 8% of patients experiencing treatment-related grade ≥3 adverse events and no treatment-related deaths reported.

The combination of MK-4166 with pembrolizumab showed promising efficacy, particularly in patients with immune checkpoint inhibitor (ICI)-naïve melanoma, achieving an objective response rate of 62%, indicating potential for effective treatment in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Papadopoulos, KP., Autio, K., Golan, T., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, showed a tolerable safety profile in 52 patients with advanced non-small-cell lung cancer (NSCLC), with 71% experiencing treatment-related adverse events, primarily fatigue and rash.

The treatment resulted in a confirmed objective response rate of 23%, with some patients achieving ongoing complete responses, and a median overall survival of 19.4 months, indicating its potential as an effective first-line therapy for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Gettinger, S., Rizvi, NA., Chow, LQ., et al.[2022]

Citations

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NCT05007782 | Study of Denikitug (GS-1811) Given Alone ... This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 ...

2. clinicaltrials.gastriccancer.org clinicaltrials.gastriccancer.org/en-US/trial/listing/300895

Study of Denikitug (GS-1811) Given Alone or With ... This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-7-2021-94cc5

GS-1811 + Zimberelimab for Solid Tumors While GLS-010 showed promising efficacy, it also had a high incidence of treatment-related adverse events (92.9%), with 28.2% of participants experiencing ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=5ba91c22-bfc5-4082-bb7c-456f3750d0e8

denikitug (GS-1811) / Gilead ... Trial completion date • Trial primary completion date • Oncology • Solid Tumor ... - "Targeting CCR8 in mouse tumor models results in robust anti-tumor efficacy ...

5. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0096.html

GS-US-570-6015; A Phase 1 Study to Evaluate the Safety, ... This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05007782?term=Gilead%20zimberelimab&rank=1

Study of GS-1811 Given Alone or With Zimberelimab in ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...