Zimberelimab for Solid Cancers

Recruiting at 15 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

182 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, GS-4528, alone or with an immune therapy in people with advanced solid tumors. The goal is to see if it is safe and to find the best dose. The combination aims to help the immune system fight cancer more effectively.

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.

What data supports the effectiveness of the drug Zimberelimab for solid cancers?

Research on similar treatments, like the bispecific antibody MEDI5752 targeting PD-1 and CTLA4, shows that targeting immune checkpoints can lead to durable responses in various tumor types, suggesting potential effectiveness for Zimberelimab, which also targets immune checkpoints. ^{1 2 3 4 5}

What makes the drug zimberelimab unique for treating solid cancers?

Zimberelimab is unique because it is a fully human monoclonal antibody that targets the PD-1 receptor, which is involved in preventing the immune system from attacking cancer cells. This mechanism is similar to other PD-1 inhibitors but zimberelimab's fully human design may reduce the risk of immune-related side effects compared to other treatments. ^{6 7 8 9 10}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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.

Positive serum pregnancy test or lactating female

Prohibited concurrent anticancer therapy listed in the protocol

Timeline

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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 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]

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 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 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]

References

1. United States 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. [2023]

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

3. United States 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. [2023]

4. United States 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. [2020]

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

Developing combination immunotherapies against cancer that make sense. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Zimberelimab: First Approval. [2022]

7. England 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. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]

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

First Tissue-Agnostic Drug Approval Issued. [2021]