What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. Targeted therapies, such as EGFR inhibitors (e.g., osimertinib) and ALK inhibitors (e.g., crizotinib), block specific proteins that promote cancer cell growth and survival. Immunotherapies, like PD-1/PD-L1 inhibitors (e.g., nivolumab), boost the immune system's ability to detect and kill cancer cells. These treatments are important for NSCLC patients as they provide more personalized and effective options, often with fewer side effects than traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab, as well as chemotherapy agents like docetaxel, etoposide, and platinum-based therapies. The known side effects of immune checkpoint inhibitors can include fatigue, rash, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, and endocrinopathies. Chemotherapy agents often cause side effects like nausea, vomiting, hair loss, fatigue, neutropenia, and an increased risk of infections. These treatments aim to improve survival and quality of life but come with a range of potential side effects that need to be managed carefully.

What prior FDA approvals exist?

The FDA has approved several targeted therapies and immunotherapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). Targeted therapies such as osimertinib (Tagrisso) for EGFR mutations, crizotinib (Xalkori) for ALK rearrangements, and entrectinib (Rozlytrek) for ROS1-positive tumors have shown significant efficacy. Immunotherapies, including pembrolizumab (Keytruda) and atezolizumab (Tecentriq), which target the PD-1/PD-L1 pathway, have also been approved for use in various settings of NSCLC. These treatments are similar to those being studied in the trial for novel treatment combinations, which aim to explore the efficacy of combining different mechanisms of action to improve patient outcomes.

What other types of research exist?

Promising novel alternatives for NSCLC treatment in 2024 include: 1) Immunotherapy combinations such as atezolizumab plus bevacizumab and chemotherapy (ABCP), which have shown improved progression-free survival (PFS) and overall survival (OS) in the IMpower 150 trial. 2) Targeted therapies for specific mutations, such as EGFR/HER2 exon 20 inhibitors like TAK-788 and poziotinib, which have demonstrated antitumor activity in clinical trials. 3) Combination regimens involving immune checkpoint inhibitors (e.g., pembrolizumab) with chemotherapy, which have shown efficacy in various subgroups of NSCLC patients. These alternatives offer new avenues for personalized and effective treatment strategies.

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Platinum-based Chemotherapy

Novel Treatment Combinations for Lung Cancer (VELOCITY-Lung Trial)

Phase 2

Recruiting

Research Sponsored by Gilead Sciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

No prior systemic treatment for metastatic NSCLC

Previously untreated individuals with resectable (Stage II, IIIA, IIIB (T[3-4]N2) NSCLC (per American Joint Committee on Cancer (AJCC) Edition 8)

Must not have

NSCLC previously treated with systemic therapy or radiotherapy

Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include typical reactions to immunotherapy such as fatigue, skin reactions, inflammation of organs like the lungs or intestines; infusion-related symptoms; blood abnormalities; increased risk of infections due to weakened immunity; and possible allergic responses specific to each drug combination used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My lung cancer is at an early stage and hasn't been treated yet.

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My planned surgery is a type of lung removal operation.

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My lung cancer diagnosis was confirmed through lab tests.

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My cancer does not have genetic changes treatable with targeted therapy.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My stage IV NSCLC is not caused by changes in the EGFR or ALK genes.

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I have received targeted therapy for my specific lung cancer mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have previously been treated with immune checkpoint inhibitors.

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I have another type of cancer that is currently active.

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I have or had lung inflammation not caused by an infection.

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My lung cancer is a mix of small-cell and non-small cell types.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Substudies 01 and 02: Objective Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Substudy 03: Complete Pathological Response (pCR) Rate

Secondary study objectives

All Substudies: Overall survival (OS)

Substudies 01 and 02: Duration of response (DOR) According to RECIST Version 1.1

Substudies 01 and 02: Progression-free Survival (PFS) According to RECIST Version 1.1

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

10Treatment groups

Experimental Treatment

Active Control

Group I: Substudy 03 - ZIM + Platinum-based ChemotherapyExperimental Treatment4 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 ChemotherapyExperimental Treatment5 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 + ETRUMAExperimental Treatment3 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 Treatment3 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 Treatment2 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 + ETRUMAExperimental Treatment2 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 Treatment3 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 ChemotherapyActive Control6 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 ChemotherapyActive Control4 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 Control2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Carboplatin

2014

Completed Phase 3

~6120

Pemetrexed

2014

Completed Phase 3

~5550

Paclitaxel

2011

Completed Phase 4

~5370

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. Targeted therapies, such as EGFR inhibitors (e.g., osimertinib) and ALK inhibitors (e.g., crizotinib), block specific proteins that promote cancer cell growth and survival. Immunotherapies, like PD-1/PD-L1 inhibitors (e.g., nivolumab), boost the immune system's ability to detect and kill cancer cells. These treatments are important for NSCLC patients as they provide more personalized and effective options, often with fewer side effects than traditional chemotherapy.

A tabulated summary of targeted and biologic therapies for non-small-cell lung cancer.