VELOCITY-Lung: A Study of Novel Treatment Combinations in Patients With Lung Cancer

Sponsor

Gilead Sciences (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05633667

Collaborator

(none)

335

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this platform clinical trial is to test novel treatment combinations in participants with lung cancer. The platform study will consist of 2 initial substudies. New substudies and/or treatment arms may be added to the study through amendment of the master protocol and/or substudy protocols.

Two initial substudies will enroll in parallel:

The goal of Substudy-01 is to see if different combinations of experimental drugs named zimberelimab, domvanalimab, sacituzumab govitecan and etrumadenant are safe and effective for persons with no prior systemic treatment as compared to standard of care.

The goal of Substudy-02 is to see if different combinations of experimental drugs named zimberelimab, sacituzumab govitecan, etrumadenant are safe and effective for persons whose cancer has progressed after receiving previous treatment for metastatic NSCLC (form of cancer that can spread from one part of body to another). The safety and effectiveness will be compared to standard of care.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer Advanced or Metastatic Non-Small-Cell Lung Cancer	Biological: Zimberelimab (ZIM) Biological: Domvanalimab (DOM) Biological: Sacituzumab govitecan-hziy (SG) Drug: Etrumadenant (ETRUMA) Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Docetaxel	Phase 2

Detailed Description

This is a Phase 2, randomized platform study to evaluate novel treatment combinations in participants with lung cancer. New substudies and/or treatment arms may be added to the study through amendment of the master protocol and/or substudy protocols.

Each substudy will consist of a preliminary stage and an expansion stage. In the preliminary stage, experimental treatment arms will be compared to the historical standard of care (SOC) benchmark.

In the expansion stage, investigational treatment arms within substudies will be compared to the comparator arm of the substudy. Not all treatment arms from preliminary stage will proceed to the expansion stage.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

335 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Platform Study Evaluating the Safety and Efficacy of Novel Treatment Combinations in Patients With Lung Cancer (VELOCITY-Lung)

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jan 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM) ZIM 360 mg and DOM 1200 mg on Day 1 of each 21-day cycle, up to 35 treatment cycles, plus SG 10 mg/kg on Days 1 and 8 of each 21-day cycle, until disease progression (PD) or unacceptable toxicity.	Biological: Zimberelimab (ZIM) Administered intravenously Other Names: AB122 GS-0122 Biological: Domvanalimab (DOM) Administered intravenously Other Names: AB154 GS-0154 Biological: Sacituzumab govitecan-hziy (SG) Administered intravenously Other Names: GS-0132 IMMU-132
Experimental: Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA) ZIM 360 mg plus DOM 1200 mg on Day 1 each 21-day cycle up to 35 treatment cycles and ETRUMA 150 mg, daily in each 21-day cycle, until PD or unacceptable toxicity.	Biological: Zimberelimab (ZIM) Administered intravenously Other Names: AB122 GS-0122 Biological: Domvanalimab (DOM) Administered intravenously Other Names: AB154 GS-0154 Drug: Etrumadenant (ETRUMA) Administered orally Other Names: AB928 GS-0928
Experimental: Substudy 01: ZIM + ETRUMA ZIM 360 mg on Day 1 of each 21-day cycle up to 35 treatment cycles plus ETRUMA 150 mg, daily in each 21-day cycle, until PD or unacceptable toxicity.	Biological: Zimberelimab (ZIM) Administered intravenously Other Names: AB122 GS-0122 Drug: Etrumadenant (ETRUMA) Administered orally Other Names: AB928 GS-0928
Active Comparator: Substudy 01: ZIM + Platinum Based Chemotherapy Expansion Stage Only: ZIM 360 mg on Day 1 of each 21-day cycle for a maximum of 35 treatment cycles plus any one of the chemotherapy (choice of chemotherapy is dependent on histology). Participants with non-squamous histology will receive: Cisplatin 75 mg/m^2 or carboplatin area under the curve (AUC) 5 plus pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle. Cisplatin/carboplatin will be administered for a maximum of 4 treatment cycles. Pemetrexed continued 4 cycles until PD or unacceptable toxicities. OR, Participants with squamous histology will receive: Carboplatin AUC 6 with paclitaxel 200 mg/m^2 on Day 1 of each 21-day cycle or nab-paclitaxel 100 mg/m^2 on Days 1, 8 and 15 of each 21-day cycle. Carboplatin, paclitaxel, and nab-paclitaxel will be administered for a maximum of 4 treatment cycles.	Biological: Zimberelimab (ZIM) Administered intravenously Other Names: AB122 GS-0122 Drug: Carboplatin Administered intravenously Drug: Cisplatin Administered intravenously Drug: Pemetrexed Administered intravenously Drug: Paclitaxel Administered intravenously Drug: Nab-paclitaxel Administered intravenously
Experimental: Substudy 02: SG + ZIM + ETRUMA ZIM 360 mg on Day 1 of each 21-day cycle up to 35 treatment cycles plus SG 10 mg/kg on Days 1 and 8 in each 21-day cycle, and ETRUMA 150 mg, daily until PD or unacceptable toxicity.	Biological: Zimberelimab (ZIM) Administered intravenously Other Names: AB122 GS-0122 Biological: Sacituzumab govitecan-hziy (SG) Administered intravenously Other Names: GS-0132 IMMU-132 Drug: Etrumadenant (ETRUMA) Administered orally Other Names: AB928 GS-0928
Active Comparator: Substudy 02: Either Docetaxel or SG (Monotherapy Only) Expansion Stage Only: Either SG 10 mg/kg on Day 1 and Day 8 of each 21-day cycle or Docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle, until PD or unacceptable toxicity.	Biological: Sacituzumab govitecan-hziy (SG) Administered intravenously Other Names: GS-0132 IMMU-132 Drug: Docetaxel Administered intravenously

Outcome Measures

Primary Outcome Measures

All Substudies: Objective Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [Up to 5 years]
ORR is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as confirmed at least 4 weeks after the first detection of response.

Secondary Outcome Measures

All Substudies: Progression-free Survival (PFS) According to RECIST Version 1.1 [Up to 5 years]
PFS is defined as the time from the date of randomization until disease progression (PD) or death, whichever comes first.
All Substudies: Duration of response (DOR) According to RECIST Version 1.1 [Up to 5 years]
DOR is defined as the time from the first response (CR or PR) until the first documented PD, or death, whichever comes first.
All Substudies: Overall survival (OS) [Up to 5 years]
OS is defined as the time from the date of randomization until death from any cause.
All Substudies: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [First dose date up to 24 months plus 100 days]
All Substudies: Percentage of Participants Experiencing Related Treatment-emergent Adverse Events (TEAEs) [First dose date up to 5 years plus 100 days]
All Substudies: Percentage of Participants Experiencing Clinical Laboratory Abnormalities [First dose date up to 5 years plus 100 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

All Substudies:

Histologically or cytologically documented non-small-cell lung cancer (NSCLC) with evidence of stage IV disease.
No known actionable genomic alterations for which approved therapies are available.
No prior systemic treatment for metastatic NSCLC.
Eastern cooperative oncology group (ECOG) performance status score of 0 or 1.
Measurable disease as per response evaluation criteria in solid tumors (RECIST) 1.1 criteria.
Adequate hematologic and end-organ function.
Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception.

Substudy 01: All Experimental arms

For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative.

Substudy 02: All Experimental arms

In individuals with nonsquamous histology, individuals with EGFR, ALK, or any other known actionable genomic alterations must have received treatment with at least 1 approved tyrosine kinase inhibitor (TKI) appropriate to the genomic alteration.
Progression or disease recurrence after platinum-based chemotherapy with anti-PD-1 or anti-PD-L1 antibody OR sequential treatment (in any order).

Key Exclusion Criteria:

All Substudies:

Mixed small-cell lung cancer and NSCLC histology.
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Received previous anticancer therapy within 4 weeks prior to enrollment.
Active second malignancy.
Active autoimmune disease.
History of or current non-infectious pneumonitis/interstitial lung disease.
Active serious infection within 4 weeks prior to study treatment.