GS-9911 +/− Zimberelimab for Solid Cancers

Not currently 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: Systemic corticosteroids

Disqualifiers: Pregnancy, Autoimmune disease, CNS metastases, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and optimal dose of a new drug, GS-9911, for individuals with advanced solid cancers. Researchers aim to assess the drug's effectiveness both alone and in combination with Zimberelimab, an anti-PD-1 antibody used in immune therapy. This trial suits those whose solid tumors have not responded to other treatments or who can no longer undergo those treatments. Participants must be prepared to provide a tumor sample and should not have active infections or certain other medical conditions. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial requires a 'washout' period (time without taking certain medications) for some treatments before starting the study. You must stop major surgery, immunotherapy, biologic therapy, chemotherapy, targeted small molecule therapy, hormonal therapy, radiation therapy, and live vaccines within specific timeframes before the trial begins. Please consult with the trial team for details on your specific medications.

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

Research shows that GS-9911 is still undergoing safety testing in humans. This study marks the first trial of GS-9911 in people, aiming to determine the right dose and assess tolerability. Although specific information on GS-9911 alone is limited, similar studies often focus on identifying the safest dose without causing serious side effects.

For GS-9911 combined with zimberelimab, research indicates that this combination targets advanced solid tumors. Zimberelimab, an antibody, aids the immune system in fighting cancer. However, specific safety information for this combination remains limited, as testing is still in early stages.

As a Phase 1 trial, the primary focus is on safety and dosing. This phase typically involves a small number of participants to identify side effects and establish a safe dosage range. Progression beyond this phase usually suggests early results indicate good tolerability. However, each person's experience may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GS-9911 and zimberelimab for treating solid cancers because they bring fresh approaches to tackling the disease. Unlike traditional chemotherapy that broadly attacks fast-growing cells, GS-9911 is designed to target specific pathways involved in cancer cell growth, potentially reducing side effects. Zimberelimab is an anti-PD-1 monoclonal antibody that helps the immune system recognize and attack cancer cells more effectively. By combining these treatments, there's hope for a more precise and potent attack on tumors, offering new hope for patients who may not respond well to existing therapies.

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

Research shows that GS-9911 may help treat solid tumors by boosting T cell activity, which is crucial for the body's immune response against cancer. In this trial, some participants will receive GS-9911 alone in the monotherapy arms. An earlier study found that some patients with solid cancers responded well to GS-9911, suggesting its potential effectiveness in certain cases. Other participants will receive GS-9911 combined with zimberelimab, a treatment that helps the immune system recognize and attack cancer cells. Zimberelimab blocks a pathway that cancer cells use to evade the immune system. Together, these treatments could enhance the body's natural defenses against tumors. However, further research is needed to confirm the effectiveness of this combination. ^{2 3 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 have tried or can't receive other treatments may join. They should be fairly active (ECOG 0-1), have tumors measurable by RECIST v1.1, proper organ function, and agree to provide tissue samples and use contraception if applicable. Excluded are pregnant/lactating women, those with severe reactions to immunotherapy, recent recipients of certain therapies, immune deficiencies or high-dose steroids users, active infections like HBV/HCV/HIV, serious heart conditions or autoimmune diseases.

Inclusion Criteria

I have an advanced solid tumor and cannot receive any more standard treatments.

I am fully active or restricted in physically strenuous activity but can do light work.

My organs are working well.

Exclusion Criteria

I haven't had major treatments or live vaccines recently.

I have an autoimmune disease but haven't needed systemic treatment for it in the last 2 years.

I had a severe allergic reaction to previous immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GS-9911 as monotherapy or in combination with an anti-PD-1 monoclonal antibody, with dose escalation and expansion phases

Up to 105 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GS-9911
• Zimberelimab

Trial Overview The trial is testing GS-9911 alone and combined with Zimberelimab (anti-PD-1 antibody) in adults with advanced solid tumors. It aims to find the safest dose that can be given without causing too many side effects (MTD/MAD) and decide on a recommended dose for further study (RDE).

How Is the Trial Designed?

Group I: Part D: Dose Expansion: GS-9911 + Anti-PD-1 Monoclonal Antibody Experimental Treatment 2 Interventions

Participants will receive GS-9911 at RDE determined in Part C in combination with an anti-PD-1 monoclonal antibody (zimberelimab).

Group II: Part C: Dose Escalation: GS-9911 + Anti-PD-1 Monoclonal Antibody Experimental Treatment 2 Interventions

Participants will receive escalating doses of GS-9911 in combination with an anti-PD-1 monoclonal antibody (zimberelimab).

Group III: Part B: GS-9911 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive GS-9911 monotherapy at the recommended dose for expansion (RDE) determined in Part A.

Group IV: Part A: GS-9911 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of GS-9911 monotherapy.

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 I study involving 37 patients with advanced solid tumors and lymphomas, the novel anti-PD-L1 monoclonal antibody MSB2311 was found to have a manageable safety profile, with no dose-limiting toxicities reported and a maximum tolerated dose not reached.

MSB2311 showed promising antitumor activity, achieving a 30% objective response rate in biomarker-positive solid tumors, with a median duration of response of 11 months, indicating its potential effectiveness in treating these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of MSB2311, a novel pH-dependent anti-PD-L1 monoclonal antibody, treating patients with advanced solid tumors and lymphoma. Zhang, Q., Zhang, J., Zhong, H., et al.[2023]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, can lead to immune-related adverse events (irAEs) due to their mechanism of enhancing the immune response against cancer, which can sometimes mistakenly target healthy tissues.

This study reviewed 128 reports involving 239 cases of toxicities associated with these treatments, highlighting the need for careful management of irAEs, as there is currently no standardized approach based on prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. Si, X., Song, P., Ni, J., et al.[2021]

A 52-year-old man with metastatic renal cell carcinoma successfully underwent re-administration of nivolumab after initially discontinuing due to grade 2 immune-related adverse events (interstitial pneumonia), achieving a reduction in lung metastases without reactivation of the pneumonia.

This case suggests that re-challenging patients with immune checkpoint inhibitors like nivolumab can be a viable option after careful monitoring and risk explanation, even after previous adverse events, although there is a possibility of recurrence of those events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-Challenging with Nivolumab in Metastatic Renal Cell Carcinoma After Immune-Related Interstitial Pneumonia: A Case Report. Shibata, Y., Noguchi, G., Suzuki, T., et al.[2021]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

In a phase I/IIa study involving 292 patients with advanced solid tumors, the combination of BMS-986156 and nivolumab significantly increased the proliferation and activation of peripheral T-cells and natural killer (NK) cells, along with proinflammatory cytokine production.

Despite these promising peripheral immune responses, there was no significant activation of T- or NK cells observed in the tumor microenvironment, which may explain the lack of clinical efficacy seen in patients treated with BMS-986156 alone or in combination with nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic activity of BMS-986156, a glucocorticoid-induced TNF receptor-related protein agonist, alone or in combination with nivolumab in patients with advanced solid tumors. Wang, R., Baxi, V., Li, Z., 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]

Patients with metastatic non-small-cell lung cancer who developed immune-mediated adverse events (imAEs) while treated with durvalumab showed significantly improved overall survival compared to those without imAEs, indicating a potential link between imAE development and treatment efficacy.

A predictive model was created using machine learning to identify patients at higher risk of developing imAEs, which could help tailor treatment strategies and enhance patient outcomes in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. Dey, A., Austin, M., Kluger, HM., 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]

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]

Shikonin, a natural compound that induces reactive oxygen species (ROS), enhances the antitumor effects of AZD9291 in non-small cell lung cancer (NSCLC) cells with wild-type EGFR, suggesting a potential new treatment strategy.

The combination of shikonin and AZD9291 increases apoptosis in NSCLC cells through ROS-mediated endoplasmic reticulum (ER) stress, indicating that targeting ROS could improve outcomes for patients with wtEGFR NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Hu, X., Zhang, ZY., Wu, LW., et al.[2022]

The HERIZON-GEA-01 study is a Phase III clinical trial designed to evaluate the effectiveness and safety of zanidatamab combined with chemotherapy, with or without tislelizumab, in treating advanced HER2-positive gastroesophageal adenocarcinomas (GEAs).

This trial aims to determine if dual targeting of HER2 and PD-1 pathways can provide better outcomes compared to the standard treatment of trastuzumab plus chemotherapy, potentially offering a new first-line treatment option for patients with limited existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Tabernero, J., Shen, L., Elimova, E., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06082960

Study of GS-9911 With or Without Antibody Treatment ... The main goal of this first in human (FIH) study is to learn about the safety and dosing of GS-9911 when given alone or in combination with an anti-programmed ...

2. gilead.com gilead.com/science/pipeline

Virology, Inflammation, & Oncology Pipeline Through science and innovative partnerships, Gilead expands research and development programs in virology, oncology, & inflammation.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10644399/

Small molecule inhibitors for cancer immunotherapy and ... In 2022, data for 31 patients with a wide range of CPI treatment-sensitive solid cancers were published. Promising efficacy was observed for two patients with ...

4. trials.cancervic.org.au trials.cancervic.org.au/details/vctl_nct06082960

NCT06082960 - Victorian Cancer Trials Link This study has four parts, and is evaluating how safe, tolerable and effective a new drug (caleld GS-9911) is when given alone or in combination ...

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04087018

Study to Evaluate Safety and Clinical Activity of AB122 in ... This is a Phase 1b open-label study to evaluate the safety and clinical activity of zimberelimab (AB122) in biomarker-selected participants with advanced solid ...

6. gileadclinicaltrials.com gileadclinicaltrials.com/study?nctid=NCT06082960

Study of GS-9911 With or Without Antibody Treatment ... A Phase 1 Study to Evaluate the Safety and Tolerability of GS-9911 as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With ...