GS-9716 + Anticancer Therapies for Advanced Solid Cancers

Not currently recruiting at 14 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: High dose corticosteroids

Disqualifiers: Pregnancy, Hepatitis, HIV, Heart failure, COPD, 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 tests a new cancer treatment called zamzetoclax (GS-9716), either alone or with other cancer drugs, to determine its safety and tolerability for people with advanced solid tumors. Researchers aim to identify the optimal dose and assess patient tolerance. Candidates may qualify if they have advanced cancer unresponsive to other treatments, particularly if they have previously undergone chemotherapy. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) for prior systemic anti-cancer therapy, but it does not specify about other medications. You may need to discuss your current medications with the trial team to see if any adjustments are necessary.

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

Research has shown that zamzetoclax (formerly GS-9716) is being tested for safety and tolerability, both alone and with other cancer drugs. Current studies aim to determine how well people handle different doses. So far, these trials have not provided specific information about side effects or negative reactions.

Since zamzetoclax is in an early trial phase, researchers are still collecting safety information. Early trials typically focus on identifying the safest dose and monitoring for side effects. This step is crucial before the drug can be used more widely. Although this does not yet provide a complete picture, it is a normal part of developing new treatments. Prospective participants should discuss potential risks and benefits with the medical team conducting the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for advanced solid cancers, like chemotherapy and targeted therapies, aim to kill cancer cells or block specific proteins that help them grow. But zamzetoclax is unique because it targets proteins that prevent cancer cells from dying, encouraging them to self-destruct. Researchers are excited about pairing zamzetoclax with drugs like docetaxel and sacituzumab govitecan-hziy because these combinations might be more effective in shrinking tumors. This approach could offer new hope for patients whose cancers have resisted standard treatments.

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

Research shows that zamzetoclax, one of the treatments in this trial, has improved outcomes in advanced cancers, such as non-small cell lung cancer, when combined with cancer treatments like docetaxel. In this trial, some participants will receive zamzetoclax with docetaxel. Docetaxel is known to extend survival and shrink tumors in some cancer patients. Another treatment option in this trial combines zamzetoclax with sacituzumab govitecan. Sacituzumab govitecan has significantly extended the time patients live without disease progression and increased tumor shrinkage, particularly in triple-negative breast cancer. These findings suggest that combining zamzetoclax with these cancer treatments could be effective for advanced solid cancers. However, further research is needed to confirm these promising early results. ^{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 have tried at least one standard treatment or for whom no standard treatment is suitable. They must be in fairly good physical condition (ECOG status of 0 or 1), have a certain level of heart, kidney, and liver function, and cannot have untreated brain metastases or serious health conditions like active hepatitis B/C or autoimmune diseases.

Inclusion Criteria

Measurable disease per RECIST version 1.1

My advanced cancer has no standard treatment available, or standard treatments have failed.

I can provide a sample of my tumor or agree to a biopsy.

Exclusion Criteria

I have a history of cancer, but not skin, early cervical, or superficial bladder cancer.

I have a history of serious heart disease or heart failure.

I haven't taken high dose steroids or had certain radiotherapy 2 weeks before starting GS-9716.

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 zamzetoclax as monotherapy or in combination with other anti-cancer agents to determine the maximum tolerated dose

Up to 105 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine
• GS-9716
• Sacituzumab Govitecan-hziy

Trial Overview GS-9716 is being tested alone and alongside other cancer drugs to find the highest dose patients can take without severe side effects. The trial will also look at how well GS-9716 works as a single agent versus when combined with established cancer treatments in people with various types of solid tumors.

How Is the Trial Designed?

Group I: Part C (Cohort C4): zamzetoclax + sacituzumab govitecan-hziy Experimental Treatment 2 Interventions

Patients will receive ≤ MTD zamzetoclax in combination with sacituzumab govitecan-hziy.

Group II: Part C (Cohort C1): zamzetoclax + docetaxel Experimental Treatment 2 Interventions

Patients will receive ≤ MTD zamzetoclax in combination with docetaxel.

Group III: Part B (Cohort B4): zamzetoclax + sacituzumab govitecan-hziy Experimental Treatment 2 Interventions

Patients will receive escalating doses of zamzetoclax in combination with sacituzumab govitecan-hziy.

Group IV: Part B (Cohort B1): Zamzetoclax + docetaxel Experimental Treatment 2 Interventions

Patients will receive escalating doses of zamzetoclax in combination with docetaxel.

Group V: Part A: zamzetoclax Dose-Expansion Experimental Treatment 1 Intervention

Patients will receive ≤ MTD of zamzetoclax.

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

Patients will receive escalating doses of zamzetoclax to estimate MTD.

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

AZD3409 demonstrated significant antineoplastic activity in breast and ovarian cancer cell lines, with varying IC50 concentrations indicating its effectiveness at different doses: 19.16 µM for MDA-MB-231 and 3.19 µM for A2780.

The mechanism of action for AZD3409 includes the inhibition of farnesylation of HDJ-2, which contributes to its cytotoxic effects, alongside differential impacts on growth factor secretion and Akt activation in breast versus ovarian cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of tumor signaling pathways by AZD3409 in vitro. Streeper, R., Campos, D., Carrizales, G., et al.[2007]

Gemcitabine has emerged as a key cytotoxic agent in the treatment of non-small cell lung cancer (NSCLC), showing effectiveness both alone and in combination with platinum-based drugs.

Pemetrexed is also proving to be a promising treatment for NSCLC and other solid tumors, with ongoing trials exploring its use as a single agent and in combination with other chemotherapy drugs like cisplatin and gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of pemetrexed (Alimta) and gemcitabine in non-small cell lung cancer. Le Chevalier, T.[2022]

Cisplatin and carboplatin, along with newer chemotherapies like docetaxel and bevacizumab, have significantly improved treatment outcomes for advanced non-small cell lung cancer (NSCLC) and are now being tested in earlier stages for potentially curative effects.

Patients with specific mutations in the EGFR gene show an 80% response rate to gefitinib, highlighting the importance of molecular profiling in tailoring treatments for NSCLC, which could lead to better management and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How today's developments in the treatment of non-small cell lung cancer will change tomorrow's standards of care. Kris, MG.[2018]

Targeted and immunological therapies have significantly improved survival rates in patients with solid tumors, demonstrating the effectiveness of treatments that focus on specific genetic and immunological changes in tumors.

Current clinical trials are exploring the optimal timing and sequencing of these therapies, which include various approved agents for cancers like prostate, breast, lung, and melanoma, indicating a shift towards more personalized cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. Grünwald, V., Rickmann, M.[2021]

ZD1839 ('Iressa') is a selective inhibitor of the epidermal growth factor receptor that effectively blocks cancer cell growth and survival, showing promising results in preclinical studies with various tumor cell lines and human tumor xenografts.

Preliminary phase I trials indicate that ZD1839 is well-tolerated and shows clinical efficacy, especially in non-small cell lung cancer (NSCLC), leading to its ongoing phase III development for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD1839 ('Iressa') as an anticancer agent. Baselga, J., Averbuch, SD.[2018]

Cisplatin-based chemotherapy has improved survival rates in advanced non-small cell lung cancer (NSCLC), and newer third-generation regimens show similar efficacy with better response rates and fewer side effects compared to older combinations.

Pemetrexed, a novel antifolate, has demonstrated comparable effectiveness to docetaxel while significantly reducing toxicities, making it a promising option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in stage-IV NSCLC. Reck, M., Gatzemeier, U.[2007]

In a study of 32 patients with brain metastases from solid tumors, the combination of temozolomide (TMZ) and cisplatin (CDDP) showed promising efficacy, with a 28.1% partial response rate and a median overall survival of 5.5 months.

The treatment was generally well-tolerated, although some patients experienced grade III-IV toxicities, including anemia and leukopenia, indicating that while the regimen is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. Christodoulou, C., Bafaloukos, D., Linardou, H., et al.[2018]

Pemetrexed is an effective treatment for advanced non-small-cell lung cancer (NSCLC), showing better outcomes in patients with nonsquamous tumors compared to those with squamous cell tumors.

The drug has a favorable safety profile and may also be beneficial as a maintenance therapy following initial treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced non-small-cell lung cancer. Fuld, AD., Dragnev, KH., Rigas, JR.[2022]

Citations

1. gileadclinicaltrials.com gileadclinicaltrials.com/study?id=GS-US-467-5643

GS-US-467-5643 This is a Phase I open-label, multi-center study of zamzetoclax (formerly GS-9716) tested either as monotherapy or in combination with other anti-cancer agents.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05006794

NCT05006794 | Study to Evaluate the Safety, Tolerability, ... This is a Phase I open-label, multi-center study of zamzetoclax (formerly GS-9716) tested either as monotherapy or in combination with other anti-cancer agents.

3. withpower.com withpower.com/trial/phase-1-neoplasms-8-2021-cf0e8

GS-9716 + Anticancer Therapies for Advanced Solid Cancers Research shows that docetaxel and gemcitabine, which are part of the treatment, have improved outcomes in advanced non-small cell lung cancer, suggesting ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-13613

Study to Evaluate the Safety, Tolerability, and ... This is a Phase I open-label, multi-center study of zamzetoclax (formerly GS-9716) tested either as monotherapy or in combination with other anti-cancer agents.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05006794/study-to-evaluate-the-safety-tolerability-and-pharmacokinetics-of-gs-9716-as-monotherapy-and-in-combination-with-anticancer-therapies-in-adults-with-solid-malignancies

Study to Evaluate the Safety, Tolerability, and ... This is a Phase I open-label, multi-center study of zamzetoclax (formerly GS-9716) tested either as monotherapy or in combination with other ...

6. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/3696/701007/Abstract-3696-GS-9716-A-potent-selective-and

Abstract 3696: GS-9716: A potent, selective and orally ... GS-9716 is currently in Phase 1 clinical trial evaluating safety, tolerability and pharmacokinetics as monotherapy and in combination with ...