Immunotherapy Combinations for Non-Small Cell Lung Cancer

(EDGE-Lung Trial)

Recruiting at 80 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

400 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{6 7 8 9 10}

What 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. ^{2 5 11 12 13}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility 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.

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.

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

Treatment Details

Interventions

• Docetaxel
• Domvanalimab
• Platinum-Based Doublet
• Quemliclustat
• Zimberelimab

Trial Overview 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.

Participant Groups

Group I: C2: Domvanalimab + Zimberelimab + Docetaxel Experimental Treatment 4 Interventions

Domvanalimab, Zimberelimab, and Docetaxel, all administered by IV infusion

Group II: C1: Quemliclustat + Zimberelimab + Docetaxel Experimental Treatment 3 Interventions

Quemliclustat, Zimberelimab, and Docetaxel, all administered by IV infusion

Group III: B5: Domvanalimab + Zimberelimab + Platinum Doublet Chemotherapy Experimental Treatment 3 Interventions

Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion

Group IV: B4: Domvanalimab + Zimberelimab + Platinum Doublet Chemotherapy Experimental Treatment 3 Interventions

Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion

Group V: B3: Domvanalimab + Quemliclustat + Zimberelimab + Platinum Doublet Chemotherapy Experimental Treatment 4 Interventions

Domvanalimab, Quemliclustat, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion

Group VI: B2: Domvanalimab + Zimberelimab + Platinum Doublet Chemotherapy Experimental Treatment 3 Interventions

Domvanalimab, Zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion

Group VII: B1: Quemliclustat + Zimberelimab + Platinum Doublet Chemotherapy Experimental Treatment 3 Interventions

Quemliclustat, zimberelimab, and platinum doublet chemotherapy, all administered by IV infusion

Group VIII: A3: Quemliclustat + Zimberelimab Experimental Treatment 2 Interventions

Quemliclustat and Zimberelimab, both administered by IV infusion

Group IX: A2: Domvanalimab + Zimberelimab Experimental Treatment 2 Interventions

Domvanalimab and Zimberelimab, both administered by IV infusion

Group X: A1: Domvanalimab + Zimberelimab Experimental Treatment 2 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

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

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Findings from Research

The introduction of new chemotherapy agents, particularly taxanes like docetaxel, has significantly improved response rates in advanced non-small cell lung carcinoma (NSCLC) from 15-20% to 25-35%, along with median survival rates increasing to 8-10 months.

Docetaxel, especially when used alone or in combination with platinols, has become a standard treatment option for NSCLC, showing promising results in both treatment-naive and previously treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced non-small cell lung carcinoma: the emerging role of docetaxel. Langer, CJ.[2019]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

Docetaxel is a highly effective treatment for advanced non-small-cell lung cancer (NSCLC), showing improved patient quality of life compared to vinorelbine-cisplatin in clinical trials, leading to its FDA approval for this indication.

With a higher binding affinity for beta tubulin than paclitaxel, docetaxel is the only chemotherapy agent approved for both first- and second-line therapy of advanced NSCLC, demonstrating its versatility and efficacy in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. Belani, CP., Eckardt, J.[2022]

Docetaxel has demonstrated a significant survival advantage in advanced non-small-cell lung cancer (NSCLC), achieving a 2-year survival rate of 12% compared to 0% for best supportive care, based on a randomized phase III trial.

When combined with other agents like cisplatin or gemcitabine, docetaxel has shown comparable or superior efficacy and response rates, making it a strong candidate for first-line treatment in NSCLC, with an acceptable toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel for locally advanced or metastatic non-small-cell lung cancer. Current data and future directions as front-line therapy. Khuri, FR.[2018]

The combination of docetaxel and cisplatin is effective for treating stage IIIB/IV non-small cell lung cancer, showing response rates between 32% and 48% and median survival times of 8 to 13 months across four phase II trials.

Docetaxel combined with carboplatin also demonstrated promising results, with a 48% response rate in a small group of 27 patients, indicating that these combinations are well tolerated and may improve outcomes if used earlier in the disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinum-based regimens in non-small cell lung cancer: results and future developments. Belani, CP.[2018]

The combination of docetaxel and gemcitabine has shown promising efficacy in treating previously untreated patients with advanced non-small cell lung cancer, achieving response rates between 25% to 50% and a median survival of 11 to 13 months, while being well tolerated with reduced neutropenia risk in weekly schedules.

Docetaxel combinations with vinorelbine and irinotecan also demonstrated comparable efficacy, with one-year survival rates of 60% and 55% respectively, suggesting these combinations could serve as effective alternatives to traditional platinum-based chemotherapy, warranting further phase III evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenging the platinum combinations in the chemotherapy of NSCLC. Douillard, JY., Eckardt, J., Scagliotti, GV.[2022]

Docetaxel, when combined with cisplatin, shows promising efficacy in treating non-small cell lung cancer, with response rates between 32% to 52% and a median survival of 8 to 12 months based on phase II studies involving various patient populations.

The combination therapy is generally well-tolerated, with neutropenia being the main dose-limiting side effect, while severe neuropathy and nephrotoxicity are rare, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: trial data and implications for clinical management. Belani, C., Lynch, T.[2018]

Docetaxel, when combined with cisplatin, shows promising efficacy in treating non-small cell lung cancer, with response rates between 32% to 52% and a median survival of 8 to 12 months based on phase II studies involving multiple patients.

The combination therapy is generally well-tolerated, with neutropenia being the main dose-limiting side effect, while severe neuropathy and nephrotoxicity are rare, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: Trial data and implications for clinical management. Belani, C., Lynch, T.[2019]

The combination of docetaxel and cisplatin showed a 45% overall response rate in 53 patients with advanced non-small-cell lung cancer (NSCLC), indicating it is an effective treatment option.

Despite its efficacy, the treatment was associated with significant hematologic toxicity, including grade 3-4 neutropenia in 23 patients, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study. Georgoulias, V., Androulakis, N., Dimopoulos, AM., et al.[2019]

The combination of gemcitabine and docetaxel was well tolerated in 32 patients with advanced, chemotherapy-naive nonsmall cell lung carcinoma (NSCLC), with manageable side effects and a low incidence of severe neutropenia (19%).

The treatment resulted in an overall response rate of 30%, with one complete response and seven partial responses, suggesting that this nonplatinum doublet could be as effective as traditional platinum-based therapies, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of gemcitabine and docetaxel in patients with chemotherapy-naive, advanced nonsmall cell lung carcinoma. Popa, IE., Stewart, K., Smith, FP., et al.[2022]

In a study of 58 patients with recurrent advanced non-small cell lung cancer (NSCLC), platinum doublet re-challenge chemotherapy showed a disease control rate of 70.7% and a median survival time of 470 days, indicating its potential efficacy as a treatment option.

The treatment was particularly effective for patients who had a partial response to first-line chemotherapy or a treatment-free interval of over 90 days, with manageable toxicity levels, except for one case of drug-induced pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the Efficacy and Safety of Platinum Doublet Re-Challenge Chemotherapy in Patients with Recurrent Advanced Non-Small Cell Lung Cancer]. Mori, A., Hirose, T., Tamura, A., et al.[2016]

In a study of 317 patients, the combination of docetaxel and gemcitabine achieved a response rate of 34%, comparable to the 32% response rate of docetaxel plus cisplatin, while causing significantly less neutropenia and gastrointestinal side effects.

Docetaxel-based combinations, such as with vinorelbine and irinotecan, have shown promising response rates and survival outcomes, with some trials reporting up to 51% response rates and 60% one-year survival, indicating their potential as effective alternatives to traditional platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-platinum based combination chemotherapy: phase I and II trials of docetaxel plus gemcitabine, vinorelbine, or irinotecan. Rigas, JR.[2022]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing improved overall survival compared to best supportive care in both first- and second-line therapies, based on randomized trials.

When combined with gemcitabine, docetaxel resulted in similar efficacy to combinations with cisplatin but caused significantly fewer severe side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel for advanced non-small cell lung cancer. Green, MR.[2018]

References

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

Advanced non-small cell lung carcinoma: the emerging role of docetaxel. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. [2022]

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

Docetaxel for locally advanced or metastatic non-small-cell lung cancer. Current data and future directions as front-line therapy. [2018]

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

Docetaxel (Taxotere) in combination with platinum-based regimens in non-small cell lung cancer: results and future developments. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Challenging the platinum combinations in the chemotherapy of NSCLC. [2022]

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

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: trial data and implications for clinical management. [2018]

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

Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: Trial data and implications for clinical management. [2019]

9. England pubmed.ncbi.nlm.nih.gov

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study. [2019]

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

A phase II trial of gemcitabine and docetaxel in patients with chemotherapy-naive, advanced nonsmall cell lung carcinoma. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

[Evaluation of the Efficacy and Safety of Platinum Doublet Re-Challenge Chemotherapy in Patients with Recurrent Advanced Non-Small Cell Lung Cancer]. [2016]

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

Non-platinum based combination chemotherapy: phase I and II trials of docetaxel plus gemcitabine, vinorelbine, or irinotecan. [2022]

13. England pubmed.ncbi.nlm.nih.gov

The current status of docetaxel for advanced non-small cell lung cancer. [2018]