Zimberelimab for Solid Cancers

Not currently recruiting at 20 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Anticancer therapy

Disqualifiers: Pregnancy, Transplantation, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GS-4528 (also known as Zimberelimab), both alone and in combination with another drug, to determine its safety and tolerability in people with advanced solid tumors. Researchers aim to identify the best dose that can be safely administered to patients. Individuals with solid tumors who have not responded to other treatments or cannot undergo those treatments might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does prohibit any anti-cancer therapy within a certain time before starting the study. It's best to discuss your current medications with the trial team to understand any specific requirements.

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

Research shows that GS-4528 is being tested for safety in people with solid tumors, either alone or with another drug called zimberelimab. Detailed safety information about GS-4528 alone is not yet available, but zimberelimab has been studied more extensively and is considered safe for patients with certain types of cervical cancer, with no new safety issues identified.

As this trial begins, researchers are determining the safest dose of GS-4528 and assessing its tolerability. Early trials like this focus on finding the right dose and monitoring patient reactions to the treatment. The safe testing of zimberelimab in other conditions is reassuring for its use in combination therapy. However, monitoring GS-4528's performance in these ongoing studies remains crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about zimberelimab and GS-4528 because they offer a novel approach to treating solid cancers. Unlike traditional chemotherapy, which targets all rapidly dividing cells, zimberelimab is an anti-PD-1 monoclonal antibody that helps the immune system recognize and attack cancer cells, making it a more targeted therapy. GS-4528, when combined with zimberelimab, might enhance this immune response even further, potentially leading to better outcomes for patients. This combination could offer a more effective treatment option with potentially fewer side effects than conventional therapies.

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

Research has shown that zimberelimab may benefit people with solid tumors. One study found that after 24 months, 71.4% of patients experienced no major disease events, and all patients remained alive. This suggests zimberelimab can extend life and slow disease progression. Another study reported a 23.6% positive response rate in patients with advanced cancers using zimberelimab alone. In this trial, participants will receive either GS-4528 monotherapy or GS-4528 combined with zimberelimab. These findings indicate that both zimberelimab and the new treatment GS-4528 could be promising options for those battling solid tumors. ^{1 2 3 6 7}

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 have tried all other treatments without success or can't tolerate them are eligible for this trial. They must be physically capable of daily activities (ECOG status 0 or 1), have measurable disease, proper organ function, and agree to use contraception if applicable. Those with autoimmune diseases, active second cancers, CNS metastases, significant heart issues, serious infections including HIV/HBV/HCV, lung conditions like pneumonitis, symptomatic fluid accumulation in the body cavities, recent vaccinations or pregnancy are excluded.

Inclusion Criteria

I can provide fresh biopsy samples before and during treatment for testing.

My organs are working well.

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria

Exclusion Criteria

I have an immune system disorder or need more than 10 mg of steroids daily.

I haven't had any cancer treatment within the specified time before starting this study.

Positive serum pregnancy test or lactating female

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody to determine the maximum tolerated dose

Up to 24 months

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GS-4528

Trial Overview The study is testing GS-4528 alone and combined with an Anti-PD-1 Monoclonal Antibody to see if they're safe and tolerable for treating solid tumors. It aims to find the highest dose patients can take without severe side effects (MTD/MAD) and recommend a Phase 2 dose (RP2D).

How Is the Trial Designed?

Group I: Phase 1b:Dose Escalation of GS-4528 in Combination With Anti-PD-1 Monoclonal Antibody (zimberelimab) Experimental Treatment 2 Interventions

Participants will receive escalating doses of GS-4528 in combination with anti-PD1 monoclonal antibody (zimberelimab) to determine the maximum tolerated dose of GS-4528 as a combination therapy.

Group II: Phase 1a: GS-4528 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive GS-4528 monotherapy at the dose determined in the escalation phase.

Group III: Phase 1a: GS-4528 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of GS-4528 monotherapy to determine the maximum tolerated dose.

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

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 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has received accelerated FDA approval for treating both adult and pediatric patients with solid tumors that are mismatch repair-deficient or microsatellite instability-high.

This approval marks a significant milestone as it is the first instance where the FDA has approved a cancer treatment based on a common biomarker rather than the specific type of tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Tissue-Agnostic Drug Approval Issued. [2021]

The anti-PD-L1 antibody ZKAB001 demonstrated a manageable safety profile in a Phase I/II study involving 21 patients with localized high-grade osteosarcoma, with the most common side effects being thyroiditis (76.2%) and dermatitis (42.9%).

Preliminary efficacy results indicated a promising 24-month event-free survival rate of 71.4% and a 100% overall survival rate, particularly benefiting patients with PD-L1 positive or MSI-H subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti-PD-L1 Antibody ZKAB001. Zhou, Y., Yang, Q., Dong, Y., et al.[2023]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

FS118, a bispecific antibody targeting LAG-3 and PD-L1, was well tolerated in a phase 1 study with 43 patients who had advanced cancer resistant to anti-PD-(L)1 therapy, showing no serious adverse events or dose-limiting toxicities.

The study demonstrated a disease control rate of 46.5%, with a higher rate of 54.8% in patients receiving doses of 1 mg/kg or greater, indicating potential efficacy in this difficult-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Yap, TA., LoRusso, PM., Wong, DJ., et al.[2023]

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]

Zimberelimab (GLS-010) is a highly effective human monoclonal antibody that binds strongly to the PD-1 receptor, blocking its interaction with PD-L1/2, which is crucial for T cell activation.

In preclinical studies, GLS-010 demonstrated significant anti-tumor effects in mice, indicating its potential as a promising treatment for cancer, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. Lou, B., Wei, H., Yang, F., et al.[2022]

In a study involving 88 patients with non-small cell lung cancer (NSCLC), the presence of serum antibodies against NY-ESO-1 and/or XAGE1 was strongly associated with a good clinical response to anti-PD-1 therapy, with an objective response rate of 65% in antibody-positive patients compared to only 19% in antibody-negative patients.

Antibody positivity was identified as a significant predictive biomarker for both progression-free survival and overall survival, outperforming other factors like tumor PD-L1 expression, indicating its potential utility in selecting patients for anti-PD-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti-Programmed Cell Death-1 Therapy in NSCLC. Ohue, Y., Kurose, K., Karasaki, T., et al.[2020]

Preclinical studies suggest that combining immunotherapies targeting PD-1 and GITR receptors could work better together than when used separately in treating human cancer.

This combination approach may enhance the immune system's ability to fight cancer, indicating a promising direction for future cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing combination immunotherapies against cancer that make sense. Veillette, A., Davidson, D.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10804044/

Efficacy and safety of zimberelimab (GLS-010) monotherapy ... In a phase Ia/Ib study, zimberelimab treatment resulted in an objective response rate of 23.6% in 284 patients with advanced lymphoma or solid ...

2. gileadclinicaltrials.com gileadclinicaltrials.com/study?nctid=NCT05840224

Study of GS-4528 in Adults With Solid Tumors The primary objectives of this study are: To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 ...

3. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2024/Arcus-Biosciences-Announces-that-Domvanalimab-Plus-Zimberelimab-Improved-Overall-Survival-in-ARC-10-a-Randomized-Study-in-Patients-with-PD-L1-High-Non-Small-Cell-Lung-Cancer/default.aspx

Press Release Details - Investors & Media - Arcus Biosciences Domvanalimab plus zimberelimab demonstrated a meaningful improvement in overall survival compared to zimberelimab alone, with a 36% reduction in risk of death.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05840224

Study of GS-4528 in Adults With Solid Tumors The goals of this clinical study are to identify if GS-4528 alone or in combination with anti-programmed cell death protein 1 (PD-1) (Anti-PD-1) Monoclonal ...

5. withpower.com withpower.com/trial/phase-1-neoplasms-4-2023-01b29

Zimberelimab for Solid Cancers · Info for Participants Preliminary efficacy results indicated a promising 24-month event-free survival rate of 71.4% and a 100% overall survival rate, particularly benefiting ...

6. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT05840224

Study of GS-4528 in Adults With Solid Tumors The primary objectives of this study are: * To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.409

Zimberelimab platform study: Safety and efficacy of ... The combination of Zim, Futi, and chemotherapy has a manageable safety profile without new safety signals and shows promising antitumor activity in pts with ...