Immunotherapy Combinations for Non-Small Cell Lung Cancer
(EDGE-Lung Trial)
Recruiting in Palo Alto (17 mi)
+80 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Gilead Sciences
Must not be taking: Corticosteroids, Immunosuppressive drugs
Disqualifiers: Autoimmune disease, Psychiatric disorders, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to assess the objective response rate (ORR) of immunotherapy-based combination therapy and to assess the safety and tolerability of immunotherapy-based combination therapy.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop taking your current medications. However, you cannot use high doses of corticosteroids or immunosuppressive medications shortly before starting the trial.
What data supports the effectiveness of the drug combinations for non-small cell lung cancer?
Research shows that docetaxel, when used alone or in combination with platinum-based drugs like cisplatin and carboplatin, improves response rates and survival in non-small cell lung cancer patients. Studies have demonstrated that these combinations can lead to better survival outcomes compared to other treatments, with manageable side effects.
12345Is the combination of docetaxel with other drugs safe for treating non-small cell lung cancer?
The combination of docetaxel with other drugs like gemcitabine, cisplatin, and carboplatin is generally well-tolerated in treating non-small cell lung cancer. Common side effects include neutropenia (low white blood cell count), but severe neuropathy (nerve damage) and nephrotoxicity (kidney damage) are uncommon.
678910What makes the drug combination of Docetaxel, Domvanalimab, and others unique for non-small cell lung cancer?
This drug combination is unique because it includes both traditional chemotherapy agents like Docetaxel and innovative immunotherapy agents like Domvanalimab, which may enhance the body's immune response against cancer cells, potentially offering a novel approach compared to standard chemotherapy alone.
25111213Eligibility Criteria
This trial is for adults with Stage IV metastatic non-small cell lung cancer (NSCLC) who have at least one measurable tumor and are in good physical condition (ECOG PS of 0 to 1). They must be able to provide a tissue sample and have their major organs functioning well. People with serious medical conditions, recent live vaccines, high-dose steroid or immunosuppressant use, psychiatric or substance abuse issues, or active autoimmune diseases can't participate.Inclusion Criteria
My organs and bone marrow are working well.
You have at least one specific area of disease that can be measured according to a certain set of guidelines.
My lung cancer is at stage IV and has spread to other parts.
+2 more
Exclusion Criteria
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of Investigational Product(s) (IPs) hazardous
I have not received any live vaccines in the last 28 days.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive immunotherapy-based combination treatments, including Domvanalimab, Zimberelimab, Quemliclustat, Docetaxel, and Platinum Doublet Chemotherapy, administered by IV infusion
12-24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Participant Groups
The study tests combinations of new drugs Quemliclustat, Zimberelimab, Domvanalimab with standard treatments like Docetaxel and Platinum-Based Doublet chemotherapy. The goal is to see how well these combinations work against NSCLC by measuring the shrinkage of tumors and evaluating the safety and comfort level of these therapies.
10Treatment groups
Experimental Treatment
Group I: C2: Domvanalimab + Zimberelimab + DocetaxelExperimental Treatment4 Interventions
Domvanalimab, Zimberelimab, and Docetaxel, all administered by IV infusion
Group II: C1: Quemliclustat + Zimberelimab + DocetaxelExperimental Treatment3 Interventions
Quemliclustat, Zimberelimab, and Docetaxel, all administered by IV infusion
Group III: B5: Domvanalimab + Zimberelimab + Platinum Doublet ChemotherapyExperimental Treatment3 Interventions
Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion
Group IV: B4: Domvanalimab + Zimberelimab + Platinum Doublet ChemotherapyExperimental Treatment3 Interventions
Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion
Group V: B3: Domvanalimab + Quemliclustat + Zimberelimab + Platinum Doublet ChemotherapyExperimental Treatment4 Interventions
Domvanalimab, Quemliclustat, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion
Group VI: B2: Domvanalimab + Zimberelimab + Platinum Doublet ChemotherapyExperimental Treatment3 Interventions
Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion
Group VII: B1: Quemliclustat + Zimberelimab + Platinum Doublet ChemotherapyExperimental Treatment3 Interventions
Quemliclustat, zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion
Group VIII: A3: Quemliclustat + ZimberelimabExperimental Treatment2 Interventions
Quemliclustat and Zimberelimab, both administered by IV infusion
Group IX: A2: Domvanalimab + ZimberelimabExperimental Treatment2 Interventions
Domvanalimab and Zimberelimab, both administered by IV infusion
Group X: A1: Domvanalimab + ZimberelimabExperimental Treatment2 Interventions
Domvanalimab and Zimberelimab, both administered by IV infusion
Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇪🇺 Approved in European Union as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇨🇦 Approved in Canada as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
🇯🇵 Approved in Japan as Taxotere for:
- Breast Cancer
- Non-small Cell Lung Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
SCRI - Tennessee Oncology - Chattanooga - Memorial PlazaNashville, TN
Hematology Oncology Associates Of The Treasure CoastPort Saint Lucie, FL
University of Alabama at Birmingham (UAB)Birmingham, AL
Memorial Cancer Institute at Memorial Regional HospitalHollywood, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Gilead SciencesLead Sponsor
Arcus Biosciences, Inc.Industry Sponsor
References
Advanced non-small cell lung carcinoma: the emerging role of docetaxel. [2019]The treatment of advanced non-small cell lung carcinoma (NSCLC) has improved greatly over the past decade. With the advent of new agents, in particular taxanes, gemcitabine, vinorelbine, and topoisomerase I inhibitors, response rates have improved from 15-20% to 25-35%, with commensurate improvement in median and one year survival rates to 8-10 months and 35-45%, respectively. These improvements have proven statistically significant in multiple studies [1-4]. Docetaxel, either alone or in combination with platinols, has shown particular promise; and, in some arenas, it has become a standard component of our therapeutic armamentarium. We will review the preclinical data and single agent activity of docetaxel in treatment-naive and previously treated NSCLC patients, its activity in combination with cisplatin and carboplatin, as well as other new agents, and finally focus on ongoing studies evaluating its role in locally advanced disease.
Docetaxel in advanced non-small cell lung cancer. [2018]Based on the survival benefit demonstrated in large randomized clinical trials, docetaxel is approved for the treatment of advanced non-small cell lung cancer (NSCLC) in both the first- and second-line settings. The efficacy of docetaxel in combination with cisplatin is equivalent to some, and superior to other, platinum-based doublets for first-line management of NSCLC, and has a manageable toxicity profile. Carboplatin-based regimens and nonplatinum combinations with docetaxel also have proven efficacy in first-line therapy of patients with advanced NSCLC. Combinations of docetaxel with various novel targeted agents have produced encouraging data in Phase II studies. This article reviews recent studies of docetaxel as a single agent and in combination regimens with cytotoxic and more recent targeted agents in the management of advanced NSCLC.
Development of docetaxel in advanced non-small-cell lung cancer. [2022]Docetaxel, a semisynthetic taxane initially developed for the treatment of breast cancer, has a high degree of activity in lung cancer. Although the mechanisms of action of the taxanes docetaxel and paclitaxel are identical, docetaxel has almost a twofold higher binding affinity for the target site, beta tubulin. In clinical trials, individuals previously treated with paclitaxel benefited from docetaxel. Docetaxel is the standard of care in second-line therapy of advanced non-small-cell lung cancer (NSCLC) and is effective, alone and in combination, in first-line treatment of advanced NSCLC. The standard in first-line therapy of metastatic NSCLC is a platinum doublet with one of the third-generation chemotherapy agents, docetaxel, paclitaxel, gemcitabine, or vinorelbine. Each of these doublets offers similar therapeutic benefit. In a phase-III study comparing docetaxel-cisplatin and docetaxel-carboplatin with vinorelbine-cisplatin, patients treated in the two docetaxel arms had consistently improved global QoL compared to patients treated with the vinorelbine-cisplatin doublet. This landmark study led to Food and Drug Administration (FDA) approval of cisplatin-docetaxel for the treatment of advanced NSCLC. Non-platinum doublets such as docetaxel-gemcitabine have also demonstrated efficacy and safety. Docetaxel has undergone extensive evaluation and is the only agent approved for use in both first- and second-line therapy of advanced NSCLC.
Docetaxel for locally advanced or metastatic non-small-cell lung cancer. Current data and future directions as front-line therapy. [2018]Docetaxel (Taxotere) has shown activity both as a single-agent and in combination with multiple other cytotoxic agents in the front-line therapy of advanced, metastatic non-small-cell lung cancer (NSCLC). A randomized, phase III trial demonstrated a survival advantage for docetaxel over best supportive care in the front-line setting, with docetaxel achieving a 2-year survival of 12% vs 0% for best supportive care. Combinations of docetaxel with the platinum agents have been the most extensively studied in the front-line setting and have produced notably high response rates and encouraging median survivals. When compared to the paclitaxel/cisplatinum combination in a large, phase III randomized trial, the combination of docetaxel and cisplatin resulted in similar response, median survival, and 1-year survival rates. Another randomized phase III trial compared docetaxel/platinum combinations to the US Food and Drug Administration (FDA)-approved vinorelbine (Navelbine)/cisplatin regimen. The docetaxel/cisplatin combination produced a superior overall survival, 2-year survival, and overall response rates compared to vinorelbine/cisplatin. The combination of docetaxel and carboplatin (Paraplatin) demonstrated similar survival and response, and was associated with quality-of-life benefits over the vinorelbine/cisplatin arm. Docetaxel has been successfully combined with gemcitabine in multiple trials with impressive response and survival rates, and an acceptable toxicity profile. A large phase IIb trial demonstrated therapeutic equivalence and lesser toxicities for the docetaxel/gemcitabine combination compared to the combination of docetaxel and cisplatin. The docetaxel/gemcitabine combination therefore represents a viable nonplatinum regimen for first-line treatment of NSCLC. Other combinations that have been tested include docetaxel with vinorelbine, and docetaxel with irinotecan (CPT-11, Camptosar). Docetaxel is active in NSCLC and should be investigated further in combination with novel molecularly targeted drugs such as tyrosine kinase inhibitors, andfarnesyl transferase inhibitors.
Docetaxel (Taxotere) in combination with platinum-based regimens in non-small cell lung cancer: results and future developments. [2018]The combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) with cisplatin is feasible, has manageable toxicity, and is active in stage IIIB/IV non-small cell lung cancer. The four phase II trials completed to date show response rates ranging from 32% to 48% and median survival durations of 8 to 13 months. Based on these results, regimens combining 75 to 100 mg/m2 docetaxel with 75 to 100 mg/m2 cisplatin are now being assessed in randomized phase III comparisons with platinum-containing combinations. The combination of docetaxel and carboplatin also has promising activity, with response rates of 48% (1 complete response and 12 partial responses) seen in 27 evaluable patients. Overall, this combination is also well tolerated. However, it will be necessary to use both docetaxel/platinum regimens at earlier stages in the disease if a significant impact is to be made on survival.
Challenging the platinum combinations in the chemotherapy of NSCLC. [2022]In previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) the combination of docetaxel and gemcitabine is active and well tolerated. In the phase II setting using a 3-week schedule, response rates (RR) ranged from 25 to 50%, and median survival from 11 to 13 months. Preliminary data with weekly and bi-weekly schedules indicate maintained efficacy while reducing the risk of neutropenia. A randomized phase III trial has shown that the combination of docetaxel and gemcitabine is as active as docetaxel plus cisplatin, achieving a 1-year survival rate of 39%, with significantly less neutropenia and gastro-intestinal toxicity. The combination of docetaxel with vinorelbine is equally active and the associated toxicities are manageable. In phase II studies the average response rate is 40%, and in one study using a 2-week schedule the 1-year survival rate was 60%. With this combination neutropenia is the commonest adverse event while clinically significant neuropathy is infrequent. In a randomized phase II trial, docetaxel plus cisplatin was compared to docetaxel plus irinotecan. The non-platinum doublet achieved comparable levels of activity, though with a different toxicity profile (more diarrhea but less nausea and vomiting). The combination of docetaxel with irinotecan and carboplatin has achieved 1-year survival of 55%. All three docetaxel combinations (gemcitabine, vinorelbine, and irinotecan) could provide a valuable alternative to platinum-based chemotherapy and should be further evaluated in phase III setting.
Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: trial data and implications for clinical management. [2018]Docetaxel (Taxotere; Aventis, Antony, France) is among the most effective agents for the treatment of non-small cell lung cancer and its use in combination with cisplatin is a logical development. Docetaxel has been combined with cisplatin and is well-tolerated with promising activity in phase II studies. Extensive phase II investigations in the first-line setting recorded response rates of 32% to 52% survival (median, 8 to 12 months) with 33% to 48% of patients alive at 1 year. Neutropenia is dose-limiting. However, the incidence of severe neuropathy is low and clinically significant nephrotoxicity is uncommon. Following these encouraging findings, the combination of docetaxel with cisplatin has been studied in two randomized phase III trials that compare the new combination against reference regimens. These studies have completed accrual and data are expected shortly. The combination of docetaxel with carboplatin is also active and feasible. Neutropenia is the main adverse event and grade II or III neurotoxicity is uncommon. In phase II trials combining doses of 65 to 100 mg/m2 docetaxel with doses of carboplatin designed to maintain an area under the curve of 5 to 7.5 mg/mL/min, response rates have ranged from 30% to 67%.
Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: Trial data and implications for clinical management. [2019]Docetaxel (Taxotere; Aventis, Antony, France) is among the most effective agents for the treatment of non-small cell lung cancer and its use in combination with cisplatin is a logical development. Docetaxel has been combined with cisplatin and is well-tolerated with promising activity in phase II studies. Extensive phase II investigations in the first-line setting recorded response rates of 32% to 52% survival (median, 8 to 12 months) with 33% to 48% of patients alive at 1 year. Neutropenia is dose-limiting. However, the incidence of severe neuropathy is low and clinically significant nephrotoxicity is uncommon. Following these encouraging findings, the combination of docetaxel with cisplatin has been studied in two randomized phase III trials that compare the new combination against reference regimens. These studies have completed accrual and data are expected shortly. The combination of docetaxel with carboplatin is also active and feasible. Neutropenia is the main adverse event and grade II or III neurotoxicity is uncommon. In phase II trials combining doses of 65 to 100 mg/m2 docetaxel with doses of carboplatin designed to maintain an area under the curve of 5 to 7.5 mg/mL/min, response rates have ranged from 30% to 67%.
First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study. [2019]To evaluate the efficacy and safety of the docetaxel-cisplatin combination in patients with advanced non-small-cell lung cancer (NSCLC).
A phase II trial of gemcitabine and docetaxel in patients with chemotherapy-naive, advanced nonsmall cell lung carcinoma. [2022]The goals of the current study were to determine the safety and efficacy of a nonplatinum-containing doublet, gemcitabine and docetaxel, in the treatment of patients with chemotherapy-naive nonsmall cell lung carcinoma (NSCLC).
[Evaluation of the Efficacy and Safety of Platinum Doublet Re-Challenge Chemotherapy in Patients with Recurrent Advanced Non-Small Cell Lung Cancer]. [2016]Docetaxel or pemetrexed is the standard treatment for recurrent advanced non-small cell lung cancer (NSCLC). Until now, combination chemotherapy has failed to demonstrate superiority in patients with recurrent advanced NSCLC, compared to single-agent chemotherapy. The aim of the present study was to assess the efficacy and safety of platinum doublet re-challenge chemotherapy in patients with recurrent advanced NSCLC.
Non-platinum based combination chemotherapy: phase I and II trials of docetaxel plus gemcitabine, vinorelbine, or irinotecan. [2022]Non-platinum combination regimens have been developed for advanced non--small cell lung cancer using the novel and active agents docetaxel, gemcitabine, vinorelbine, and irinotecan. The aim of these combinations is to equal or exceed the survival benefits achieved with cisplatin doublets while minimizing toxicity. Of the docetaxel-based combinations, gemcitabine has been the most extensively studied. In a 317-patient randomized trial, docetaxel plus gemcitabine achieved a response rate of 34%, similar to the 32% response rate seen in patients randomized to docetaxel plus cisplatin. One-year survival rates were 38% and 42%, respectively. While being equally active, the docetaxel/gemcitabine combination was associated with significantly less neutropenia and gastrointestinal adverse events than the cisplatin-containing regimen. Phase II trials of docetaxel plus vinorelbine have reported response rates of up to 51% and 1-year survival in up to 60% of patients without significant peripheral neuropathy. Docetaxel plus irinotecan is also active in advanced non--small cell lung cancer and has shown similar efficacy to docetaxel plus cisplatin in a randomized trial. The adverse event profile of docetaxel/irinotecan is different from that of cisplatin-based regimens. Both non-platinum and platinum combination regimens have an important role to play in the treatment of non--small cell lung cancer. Semin Oncol 28 (suppl 9):15-20.
The current status of docetaxel for advanced non-small cell lung cancer. [2018]Docetaxel is an active single agent in both first- and second-line therapy of patients with advanced non-small cell lung cancer (NSCLC). Randomized trials versus best supportive care have documented an improvement in overall survival for docetaxel therapy in both settings. Docetaxel also produced a significant 1-year survival rate improvement when compared with vinorelbine or ifosfamide as second-line therapy. Docetaxel has been extensively investigated in phase I/II studies in combination with cisplatin, carboplatin, irinotecan and gemcitabine. Substantial activity has been demonstrated. In a randomized phase II trial comparing docetaxel plus cisplatin with docetaxel plus gemcitabine, the efficacy of the two regimens was almost identical (response rates 32 and 34%; 1-year survival rates 42 and 38%). However, the combination of docetaxel with gemcitabine was associated with significantly less grade III/IV neutropenia, diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are producing very high response rates in phase II trials. Whether three-drug combinations including docetaxel will result in an improved outcome for patients with advanced NSCLC remains to be determined.