Novel Treatment Combinations for Lung Cancer

(VELOCITY-Lung Trial)

Recruiting in Palo Alto (17 mi)

+85 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: Immune checkpoint inhibitors

Disqualifiers: Active malignancy, Autoimmune disease, Pneumonitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing new treatment combinations for lung cancer to see if they work better than current treatments. It focuses on patients with advanced or resectable lung cancer, including those who haven't been treated before or whose cancer has worsened after treatment. The goal is to find out if these new combinations can shrink or eliminate tumors more effectively.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have received previous anticancer therapy within 4 weeks prior to enrollment, you may not be eligible for Substudy 01 and 02.

What data supports the idea that Novel Treatment Combinations for Lung Cancer is an effective drug?

The available research shows that combining paclitaxel and carboplatin is promising for treating non-small-cell lung cancer. In one study, this combination resulted in a 54% one-year survival rate, which is higher than the 40% rate seen with paclitaxel alone. Another study found a 27.5% response rate with this combination, indicating that it helps some patients' tumors shrink or stop growing. Additionally, docetaxel combined with cisplatin showed response rates between 32% and 48%, with survival times ranging from 8 to 13 months. These combinations are generally well-tolerated, meaning they don't cause severe side effects for most patients. Compared to older treatments, these new combinations offer better survival rates and fewer side effects, making them effective options for lung cancer treatment. ^{1 2 3 4 5}

What safety data is available for the lung cancer treatment involving these drugs?

The safety data for the treatment involving combinations of drugs like paclitaxel, carboplatin, and docetaxel in non-small cell lung cancer (NSCLC) shows that these combinations have been studied for their efficacy and toxicity. Paclitaxel and carboplatin have been used together in multiple studies, showing modest toxicity with myelosuppression being the most common side effect. Nonhematologic toxicities were generally low, with fewer than 5% of patients experiencing severe side effects. The combination of docetaxel with either cisplatin or carboplatin also showed tolerable hematologic toxicities and a low rate of febrile neutropenia. Nonhematologic toxicities like nausea and vomiting were less frequent with docetaxel plus carboplatin compared to other regimens. Overall, these combinations have been well-tolerated and are widely used in community practice for NSCLC. ^{2 3 6 7 8}

Is the drug combination of Carboplatin, Cisplatin, Docetaxel, Domvanalimab, Etrumadenant, Nab-paclitaxel, Paclitaxel, Pemetrexed, Sacituzumab govitecan-hziy, and Zimberelimab promising for lung cancer?

Yes, the combination of Carboplatin and Paclitaxel shows promise for treating lung cancer. Studies have shown that this combination can improve survival rates and is widely used in practice. It is also well-tolerated, especially in elderly patients, making it a promising option for lung cancer treatment. ^{2 3 9 10 11}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with untreated, measurable non-small cell lung cancer (NSCLC), including those with metastatic or resectable stage II-III NSCLC. Participants must have good organ function and performance status, no known genetic mutations treatable by targeted therapies unless previously treated, and agree to use contraception if applicable. Exclusions include prior systemic or radiotherapy for NSCLC, active brain metastases, history of immune checkpoint inhibitor treatment, other cancers, autoimmune diseases, lung conditions like pneumonitis or infections.

Inclusion Criteria

Your PD-L1 status needs to be confirmed by a central laboratory.

I haven't had any systemic treatment for my advanced lung cancer.

My planned surgery is a type of lung removal operation.

Exclusion Criteria

I have not had a serious infection in the last 4 weeks.

I have received treatments like chemotherapy or radiotherapy for my lung cancer.

I have cancer that has spread to my brain or surrounding membranes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive novel treatment combinations or standard of care until disease progression, unacceptable toxicity, or protocol specified discontinuation criteria are met

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Carboplatin (Platinum-based Chemotherapy)
• Cisplatin (Platinum-based Chemotherapy)
• Docetaxel (Taxane-based Chemotherapy)
• Domvanalimab (Monoclonal Antibodies)
• Etrumadenant (Adenosine Receptor Antagonist)
• Nab-paclitaxel (Taxane-based Chemotherapy)
• Paclitaxel (Taxane-based Chemotherapy)
• Pemetrexed (Antimetabolite-based Chemotherapy)
• Sacituzumab govitecan-hziy (Antibody-drug Conjugate)
• Zimberelimab (Monoclonal Antibodies)

Trial Overview The study tests novel combinations of drugs Etrumadenant (ETRUMA), Zimberelimab (ZIM), Domvanalimab (DOM) etc., against standard chemotherapy treatments in three substudies: one for first-time treatment in metastatic NSCLC patients; another for those whose cancer progressed after initial therapy; and a third for early-stage patients eligible for surgery. Effectiveness will be measured by tumor response rate or complete pathological response post-treatment.

Participant Groups

Group I: Substudy 03 - ZIM + Platinum-based Chemotherapy Experimental Treatment 4 Interventions

Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).

Group II: Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy Experimental Treatment 5 Interventions

Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).

Group III: Substudy 02: SG + ZIM + ETRUMA Experimental Treatment 3 Interventions

Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Group IV: Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM) Experimental Treatment 3 Interventions

Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.

Group V: Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) Experimental Treatment 2 Interventions

Participants will receive ZIM and SG until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.

Group VI: Substudy 01: ZIM + ETRUMA Experimental Treatment 2 Interventions

Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Group VII: Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA) Experimental Treatment 3 Interventions

Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Group VIII: Substudy 01: ZIM + Platinum Based Chemotherapy Active Control 6 Interventions

Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).

Group IX: Substudy 03: Nivolumab + Platinum-based Chemotherapy Active Control 4 Interventions

Participants will receive nivolumab plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).

Group X: Substudy 02: Either Docetaxel or SG (Monotherapy Only) Active Control 2 Interventions

Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular 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 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 paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

Docetaxel-cisplatin is the most effective taxane-platinum combination for treating non-small cell lung cancer (NSCLC), showing superior survival and response rates compared to other platinum combinations in large clinical trials involving chemotherapy-naïve patients.

Paclitaxel-carboplatin has a lower incidence of severe neutropenia but is associated with higher rates of irreversible peripheral neuropathy, highlighting the need to consider both efficacy and side effects when choosing treatment options for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane-platinum combinations in advanced non-small cell lung cancer: a review. Rigas, JR.[2022]

In a multicenter study involving 130 patients with advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel and carboplatin resulted in a moderate response rate of 23.8%, indicating its efficacy as a treatment option.

Both high-dose (200 mg/m2) and low-dose (175 mg/m2) paclitaxel regimens were well tolerated, with myelosuppression being the most significant side effect, but differences in toxicity between the two doses were minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). Glorieux, P., Ortmanns, P., Marien, S., et al.[2015]

In a study comparing carboplatin combined with either paclitaxel or docetaxel in four ovarian carcinoma cell lines, both combinations showed a synergistic effect, enhancing the growth inhibitory impact on cancer cells.

The combination of carboplatin with paclitaxel produced a broader range of supra-additive effects across various concentrations compared to the carboplatin-docetaxel combination, suggesting that paclitaxel may be more effective in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-paclitaxel- and carboplatin-docetaxel-induced cytotoxic effect in epithelial ovarian carcinoma in vitro. Engblom, P., Rantanen, V., Kulmala, J., et al.[2019]

In the TAX 326 trial involving 1,220 patients with advanced non-small cell lung cancer, docetaxel combined with either cisplatin or carboplatin showed a high relative dose intensity of 0.97, indicating effective dosing compared to vinorelbine, which had a lower intensity of 0.68 due to more frequent dose reductions.

Hematologic toxicities were manageable across all treatment groups, with febrile neutropenia rates below 5%, and patients receiving docetaxel plus carboplatin experienced less nausea and vomiting compared to those on other regimens, suggesting a potentially better tolerability profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial of docetaxel in combination with cisplatin or carboplatin or vinorelbine plus cisplatin in advanced non--small cell lung cancer: interim analysis. Belani, C.[2018]

In a study of 24 patients with advanced non-small cell lung cancer, the combination of paclitaxel and cisplatin resulted in significantly lower clearance of paclitaxel compared to when it was combined with gemcitabine, indicating a potential interaction that could affect dosing.

The combination of gemcitabine with either cisplatin or paclitaxel led to a significantly higher decrease in platelet counts, suggesting increased toxicity, but pharmacologic parameters did not correlate with treatment response or survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin, and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer. Kroep, JR., Smit, EF., Giaccone, G., et al.[2022]

References

1. 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]

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

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]

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

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Taxane-platinum combinations in advanced non-small cell lung cancer: a review. [2022]

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

Rationale for non-platinum chemotherapy in advanced NSCLC. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). [2015]

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

Carboplatin-paclitaxel- and carboplatin-docetaxel-induced cytotoxic effect in epithelial ovarian carcinoma in vitro. [2019]

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

Phase III randomized trial of docetaxel in combination with cisplatin or carboplatin or vinorelbine plus cisplatin in advanced non--small cell lung cancer: interim analysis. [2018]

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

Gemcitabine/carboplatin combination regimens: importance of dose schedule. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin, and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer. [2022]