GS-9716 + Anticancer Therapies for Advanced Solid Cancers
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Gilead Sciences
Must not be taking: High dose corticosteroids
Disqualifiers: Pregnancy, Hepatitis, HIV, Heart failure, COPD, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial is testing a new cancer drug called GS-9716 in patients with advanced solid cancers. The goal is to find the highest safe dose and see if it causes any serious side effects, both alone and with other treatments.
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.
What data supports the effectiveness of the drug GS-9716 combined with other anticancer therapies for advanced solid cancers?
What makes the drug GS-9716 unique for treating advanced solid cancers?
GS-9716, also known as zamzetoclax, is unique because it is being studied in combination with other anticancer therapies for advanced solid cancers, potentially offering a novel approach compared to existing treatments. While the specific mechanism of action for GS-9716 is not detailed in the provided research, its combination with other therapies suggests it may enhance treatment effectiveness or reduce side effects.13678
Eligibility Criteria
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.
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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.
See 17 more
Trial Timeline
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
Treatment Details
Interventions
- Docetaxel (Chemotherapy)
- Gemcitabine (Chemotherapy)
- GS-9716 (Other)
- Sacituzumab Govitecan-hziy (Monoclonal Antibodies)
Trial OverviewGS-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.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Part C (Cohort C4): zamzetoclax + sacituzumab govitecan-hziyExperimental Treatment2 Interventions
Patients will receive ≤ MTD zamzetoclax in combination with sacituzumab govitecan-hziy.
Group II: Part C (Cohort C1): zamzetoclax + docetaxelExperimental Treatment2 Interventions
Patients will receive ≤ MTD zamzetoclax in combination with docetaxel.
Group III: Part B (Cohort B4): zamzetoclax + sacituzumab govitecan-hziyExperimental Treatment2 Interventions
Patients will receive escalating doses of zamzetoclax in combination with sacituzumab govitecan-hziy.
Group IV: Part B (Cohort B1): Zamzetoclax + docetaxelExperimental Treatment2 Interventions
Patients will receive escalating doses of zamzetoclax in combination with docetaxel.
Group V: Part A: zamzetoclax Dose-ExpansionExperimental Treatment1 Intervention
Patients will receive ≤ MTD of zamzetoclax.
Group VI: Part A: zamzetoclax Dose-EscalationExperimental Treatment1 Intervention
Patients will receive escalating doses of zamzetoclax to estimate MTD.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Novant Health Cancer Institute - Elizabeth (Breast Cancer)Charlotte, NC
Stephenson Cancer CenterOklahoma City, OK
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)Aurora, CO
Moffitt Cancer CenterTampa, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Gilead SciencesLead Sponsor
References
How today's developments in the treatment of non-small cell lung cancer will change tomorrow's standards of care. [2018]Cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb), together with newer chemotherapies, such as docetaxel (Taxotere; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol; Bristol-Myers Squibb), vinorelbine (Navelbine; GlaxoSmith-Kline, Philadelphia, http://www.gsk.com), pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, http://www.lilly.com), and gemcitabine (Gemzar; Eli Lilly and Company), have improved treatment outcomes in both advanced non-small cell lung cancer (NSCLC) and in the adjuvant/neoadjuvant setting. Newer systemic treatments for NSCLC, used in advanced stage IV management, are beginning to be studied in earlier stages of the disease, when treatment is better tolerated and potentially curative. Hopefully, newer agents with proven efficacies in advanced disease will enhance curability. Following the successful addition of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to carboplatin/paclitaxel in advanced disease, bevacizumab is now being incorporated into adjuvant and neoadjuvant trials. Trials in stage IB-IIIA patients will study neoadjuvant docetaxel/cisplatin/bevacizumab. The discovery that patients with exon 19 and 21 mutations in the epidermal growth factor receptor gene EGFR have around an 80% response rate to gefitinib (Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE, http:// www.astrazeneca-us.com) and that this response confers survival benefit indicates its potential utility for mutation-positive patients with advanced- and earlier-stage disease. Clinical characteristics, such as never smoking status and adenocarcinoma, and especially bronchioloalveolar carcinoma histological features, can also identify individuals likely to respond to EGFR tyrosine kinase inhibitors. Studies of neoadjuvant erlotinib (Tarceva; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com) in operable NSCLC are planned. One such study includes cisplatin and docetaxel. Effective development of active agents and disease management based on molecular profiling of lung tumors will change tomorrow's standard of care.
Regulation of tumor signaling pathways by AZD3409 in vitro. [2007]The antineoplastic activity of AZD3409 was evaluated in relation to paclitaxel in human breast (MDA-MB-231, BT-474) and ovarian (A2780, A2780cp) cancer cell lines. Biomarkers of apoptosis, protein prenylation, survival, angiogenesis and cellular growth were determined.
Chemotherapy in stage-IV NSCLC. [2007]Since cisplatin-based chemotherapy was proven to increase survival in advanced and metastatic NSCLC various new combinations have been tested. The third generation regimens which showed almost comparable efficacy among each other in randomised trials often proved a better response rate and time to progression combined with a remarkable reduction of toxic side effects compared to "classic" combinations, whereas most studies only noted a modest increase in survival. Two-drug regimens were more effective than monotherapy but at the expense of significantly increased toxicity, while monotherapy compared to BSC improved quality of life and survival. The novel antifolate Pemetrexed proved comparable activity to docetaxel with significantly reduced toxicities.
ZD1839 ('Iressa') as an anticancer agent. [2018]ZD1839 ('Iressa') is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and other host-dependent processes promoting cancer growth. In preclinical studies, ZD1839 produced reversible growth inhibition and growth delay in a wide range of tumour cell lines and human tumour xenografts. Moreover, this activity was enhanced when ZD1839 was coadministered with cytotoxic agents. Preliminary results from phase I trials in patients with advanced disease and a wide variety of tumour types suggest that ZD1839 has an acceptable tolerability profile and promising clinical efficacy, particularly in non-small cell lung cancer (NSCLC). ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC. In addition, further trials are ongoing or planned in a number of other tumour types.
Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. [2018]To evaluate the efficacy of temozolomide (TMZ) combined with cisplatin (CDDP) in terms of response rate, time to progression (TTP) and overall survival (OS), as well as the tolerability of the regimen in patients with brain metastases from solid tumors.
[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.
Pemetrexed in advanced non-small-cell lung cancer. [2022]Current therapeutic options for advanced non-small-cell lung cancer (NSCLC) yield relatively modest improvements in survival leading to an ongoing search for new active treatment agents. In the past decade, pemetrexed has had an increasingly established role in the treatment of advanced NSCLC in both first- and second-line settings.
The emerging role of pemetrexed (Alimta) and gemcitabine in non-small cell lung cancer. [2022]In recent years, several new cytotoxic agents have been investigated for the management of non-small cell lung cancer (NSCLC), including the antimetabolic gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and the new multitargeted antifolate pemetrexed (Alimta, Eli Lilly and Company), which are both among the most active agents in advanced NSCLC. Gemcitabine has become one of the key drugs in the management of NSCLC, alone or in association with platin compounds. Promising results have also been reported with pemetrexed used as a single-agent or in combination with cisplatin or gemcitabine. These results indicate that pemetrexed may also play a vital role in the treatment of NSCLC, malignant mesothelioma, and other solid tumors. Ongoing (and planned) trials are investigating the use of single-agent pemetrexed, or combinations with cisplatin, gemcitabine, and other cytotoxic agents in various malignancies.