GS-2121 + Zimberelimab for Cancer

Recruiting at 5 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Antiarrhythmics, Antivirals, Antifungals, others

Disqualifiers: Pregnancy, CNS metastases, 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 105 weeks

154 Participants Needed

Trial Summary

What is the purpose of this trial?

The main goal of this first-in-human (FIH) study is to learn about the safety and dosing of GS-2121 when given alone or in combination with zimberelimab (ZIM) in participants with advanced solid tumors. The primary objectives of this study are: * To assess the safety and tolerability of GS-2121 as monotherapy and GS-2121 in combination with zimberelimab in participants with advanced solid tumors. * To identify the maximum tolerated dose (MTD) / maximum administered dose (MAD) and/or the recommended phase 2 dose (RP2D) of GS-2121 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, including any anti-cancer therapies, major surgeries, and some other treatments within specific time frames. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug GS-2121 + Zimberelimab for cancer?

Research on similar treatments shows that combining different immunotherapy drugs, like PD-1 inhibitors, can improve long-term survival in various cancers. This suggests that combining GS-2121 and Zimberelimab might also enhance cancer treatment effectiveness. ^{1 2 3 4 5}

What makes the drug GS-2121 + Zimberelimab unique for cancer treatment?

The combination of GS-2121 and Zimberelimab is unique because Zimberelimab is a monoclonal antibody that targets the PD-1 protein, which helps the immune system recognize and attack cancer cells. This approach is part of a newer class of cancer treatments that enhance the body's immune response against tumors. ^{5 6 7 8 9}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with advanced solid tumors who are eligible to receive new treatments. Specific eligibility criteria aren't provided, but typically participants must have measurable disease and adequate organ function, and cannot be receiving other cancer therapies.

Inclusion Criteria

My advanced cancer has not responded to standard treatments, or I cannot undergo them.

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

I am fully active or can carry out light work.

Exclusion Criteria

I have active brain metastases or leptomeningeal disease.

Have not recovered from adverse events due to a previously administered agent

I have been diagnosed with an immune system disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GS-2121 as monotherapy or in combination with zimberelimab, with dose escalation and expansion phases

Up to 105 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• GS-2121
• Zimberelimab

Trial Overview The study is testing GS-2121 alone or combined with zimberelimab (ZIM) in patients with advanced solid tumors. It aims to determine the safety, tolerability, and optimal dosing of these treatments.

Participant Groups

Group I: Part D: Combination Dose Expansion of GS-2121 with Zimberelimab Experimental Treatment 2 Interventions

Participants with selected indications will receive GS-2121 at the recommended dose for expansion in combination with zimberelimab.

Group II: Part C: Combination Dose Escalation of GS-2121 with Zimberelimab Experimental Treatment 2 Interventions

Participants will receive escalating doses of GS-2121 in combination with zimberelimab until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.

Group III: Part B: GS-2121 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants with selected indications will receive GS-2121 monotherapy at the recommended dose for expansion.

Group IV: Part A: GS-2121 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of GS-2121 monotherapy until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.

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

PD-1/PD-L1 inhibitors have limited effectiveness in patients with low PD-L1 expression in advanced non-small cell lung cancer (NSCLC), highlighting the need for improved treatment options.

Dual immunotherapy, combining PD-1 and CTLA-4 inhibitors, shows promise for better long-term survival in NSCLC, with ongoing research focused on identifying optimal patient groups and ensuring safety through multidisciplinary approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dual Immunotherapy in Advanced Non-small Cell Lung Cancer: the Progress and Clinical Application]. Deng, H., Wang, L., Yang, Y., et al.[2022]

TSAxCD28 bispecific antibodies can enhance the effectiveness of anti-PD-1 therapy, enabling immune responses and long-term memory against tumors that typically do not respond to PD-1 blockers, as demonstrated in preclinical models.

These bispecifics show minimal toxicity compared to other T cell activators, making them a promising and safe addition to cancer immunotherapy regimens, potentially improving outcomes for patients with resistant tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. Waite, JC., Wang, B., Haber, L., et al.[2021]

AMG 228, a monoclonal antibody targeting GITR, was well tolerated in a phase 1 study with 30 patients, reaching a maximum dose of 1200 mg without any dose-limiting toxicities, indicating a favorable safety profile.

Despite achieving target coverage and favorable pharmacokinetics, AMG 228 did not demonstrate T-cell activation or anti-tumor activity in patients with advanced solid tumors, suggesting that further investigation is needed to assess its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor-related protein agonist AMG 228 in patients with advanced solid tumors. Tran, B., Carvajal, RD., Marabelle, A., et al.[2019]

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]

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

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]

Sasanlimab, an antibody targeting the PD-1 receptor, was well tolerated in patients with non-small-cell lung cancer (NSCLC) and urothelial carcinoma, with only 13.2% experiencing severe treatment-related side effects.

The treatment showed promising efficacy, with objective response rates of 16.4% in NSCLC and 18.4% in urothelial carcinoma, particularly in patients with high PD-L1 expression and tumor mutational burden, suggesting it may be a viable option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/II dose expansion study of subcutaneous sasanlimab in patients with locally advanced or metastatic non-small-cell lung cancer and urothelial carcinoma. Cho, BC., Penkov, K., Bondarenko, I., et al.[2023]

Dostarlimab, an investigational anti-PD-1 monoclonal antibody, shows promising clinical activity, especially in treating endometrial cancer, indicating its potential as a new treatment option.

This antibody is being explored both alone and in combination with other therapies for various cancers, including gynecological tumors, lung cancer, and melanoma, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. Rubio-Pérez, J., Hernández, R., Hernández, T., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Dual Immunotherapy in Advanced Non-small Cell Lung Cancer: the Progress and Clinical Application]. [2022]

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

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor-related protein agonist AMG 228 in patients with advanced solid tumors. [2019]

4. United States 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. [2022]

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

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. [2023]

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. England pubmed.ncbi.nlm.nih.gov

A phase Ib/II dose expansion study of subcutaneous sasanlimab in patients with locally advanced or metastatic non-small-cell lung cancer and urothelial carcinoma. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021]