Novel Treatment Combinations for Lung Cancer

(VELOCITY-Lung Trial)

Recruiting at 130 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Active malignancy, Autoimmune disease, Pneumonitis, 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: Up to 5 years

593 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatment combinations for people with different stages of lung cancer. It compares the effectiveness of these treatments to the usual care for patients with non-small-cell lung cancer (NSCLC) that hasn't been treated before, has progressed after previous treatment, or is potentially removable by surgery. Participants should have NSCLC without certain known mutations and either have not received treatment for metastatic NSCLC or have cancer that can be surgically removed but have not been treated yet.

As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in lung cancer treatment.

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.

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

Research shows that the treatments in this trial have undergone prior safety testing in humans.

Zimberelimab, an immune therapy, has been tested with several other drugs. Studies indicate that when combined with sacituzumab govitecan, this combination is generally safe, though it can cause risks such as a drop in white blood cells, potentially leading to infections, and diarrhea.

Adding domvanalimab to zimberelimab and sacituzumab govitecan has also been studied. Research from another study suggests that this combination is well-tolerated, but like many cancer treatments, it can cause side effects such as tiredness or changes in blood counts.

Zimberelimab combined with etrumadenant is another combination under investigation. Previous studies show this pair is generally safe and well-tolerated at all doses tested. Earlier trials noted that etrumadenant is well-tolerated by patients.

When zimberelimab, domvanalimab, and etrumadenant are used together, research suggests they are safe for patients previously treated for lung cancer, though side effects can still occur.

The phase of this trial indicates that these treatments have already shown some evidence of safety. This means they are considered safe enough for further testing in more people, but they are still being studied to better understand all potential risks. Participants should be aware that while these treatments have been tested before, side effects remain possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they explore new combinations that could enhance the effectiveness of existing therapies. Unlike the current standard chemotherapy options like carboplatin and cisplatin, the investigational treatments involve advanced agents like Zimberelimab (ZIM) and Sacituzumab govitecan-hziy (SG), which are designed to boost the immune system's response to cancer. Zimberelimab is a checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Meanwhile, Sacituzumab govitecan-hziy is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, sparing more healthy cells in the process. These innovative combinations could potentially offer more targeted and potent treatment options for lung cancer patients.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that combining zimberelimab and sacituzumab govitecan-hziy, which participants in this trial may receive, holds promise for treating lung cancer. Studies have found that sacituzumab govitecan-hziy can lower the risk of disease progression or death, yielding better results than standard chemotherapy. In this trial, some participants will receive zimberelimab with domvanalimab, which improved overall survival, reducing the risk of death by 36% compared to zimberelimab alone. Domvanalimab also enhances the overall response when used with zimberelimab. For patients previously treated for lung cancer, combining zimberelimab with etrumadenant, another treatment option in this trial, significantly lowered the risk of disease progression by 73%. These findings suggest that these treatment combinations could offer effective new options for lung cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Domvanalimab
• Etrumadenant
• Nab-paclitaxel
• Paclitaxel
• Pemetrexed
• Sacituzumab govitecan-hziy
• Zimberelimab

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

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+

Published Research Related to This Trial

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]

Combining gemcitabine with carboplatin has shown improved response and survival rates in patients with advanced non-small-cell lung cancer compared to older platinum-based treatments.

Carboplatin, due to its lower nonhematologic toxicities, has allowed for the development of new combination therapies that enhance the efficacy and tolerability of cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin combination regimens: importance of dose schedule. Gandara, DR., Lau, DH., Lara, PN., et al.[2022]

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]

Five new cytotoxic drugs have been introduced for treating non-small-cell lung cancer (NSCLC), showing comparable activity to cisplatin when used alone, and improved survival when combined with cisplatin.

Randomized studies indicate that these newer drugs not only enhance survival rates but also reduce side effects compared to older chemotherapy regimens, suggesting they are valuable options for patients, including those previously treated with platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a phase II trial involving 32 elderly patients with untreated advanced non-small cell lung cancer, the combination of weekly nanoparticle albumin-bound-paclitaxel and carboplatin showed a 50% overall response rate and a median overall survival of 17.5 months, indicating significant efficacy.

The treatment was well tolerated, with no treatment-related deaths or febrile neutropenia reported, and it resulted in less neuropathic toxicity compared to traditional regimens, making it a promising option for elderly patients.

NCBI (Pubmed)

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. Miyauchi, E., Inoue, A., Usui, K., et al.[2018]

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]

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]

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]

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]

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 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]

Citations

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Docetaxel in the treatment of non-small cell lung carcinoma Median survival was 10.9 months, with a median time to progression 5.0 months, suggesting this may be a viable alternative to three-weekly dosing in the elderly ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e21197

Docetaxel as a subsequent line after progression to ... Conclusions: Docetaxel displayed poor survival results in our study after progression to platinum-based chemotherapy and ICIs, arising the ...

3. ar.iiarjournals.org ar.iiarjournals.org/content/33/9/3831

Docetaxel in the Treatment of Non-small Cell Lung Cancer ... Results: The pre-existing symptoms of cough, dyspnea and pain markedly improved after three cycles of docetaxel-based therapy. Regression of symptoms was ...

4. cancernetwork.com cancernetwork.com/view/docetaxel-previously-treated-non-small-cell-lung-cancer

Docetaxel for Previously Treated Non-Small-Cell Lung ... Median survival was 7.5 months with docetaxel at 75 mg/m² (D75) vs 4.6 months for best supportive care (P = .010); and 1-year survival was 37% for D75 vs 11% ...

5. oncotarget.com oncotarget.com/article/28444/text/

Value of chemotherapy post immunotherapy in stage IV ... Our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04791839

Study Details | NCT04791839 | Safety and Efficacy of ... Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small ...

7. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(23)00267-X/abstract

A Phase III Randomized Study of Domvanalimab and ... The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti–PD-1) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04736173

NCT04736173 | Study Evaluating Effectiveness and Safety ... This is a phase 2 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) in front-line, PD-L1-high, locally advanced or metastatic ...

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Anti-TIGIT Domvanalimab-Based Combinations Showed ... Anti-TIGIT Domvanalimab-Based Combinations Showed Encouraging Clinical Activity in People with Metastatic, PDL1-High Non-Small Cell Lung Cancer ...

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Study Evaluating Effectiveness and Safety of Zimberelimab ... This is a phase 2 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) in front-line, PD-L1-high, locally advanced or metastatic ...