Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer

Phase
Recruitment status
Active, not recruiting
Participants
Lead sponsor
Gilead Sciences
Start date
Number of sites

Summary
The primary objective of this study is to compare the effect of zimberelimab (ZIM) and domvanalimab (DOM) in combination with chemotherapy relative to pembrolizumab (PEMBRO) in combination with chemotherapy on overall survival (OS) in patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration.
Acronym
Short title
Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer
Official title
A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations

Control arm
Active comparator
Registry reports results
Listing at source
Recruitment status
Active, not recruiting
Phase
Study type
Interventional

Completion date
First posted
Registry last updated
Primary completion date
Start date

Actual participants
Participants
Participant count basis
Protocol amendments
Number of sites

Data monitoring committee
Registry sponsor category
Lead sponsor
Gilead Sciences
Source registry
ClinicalTrials.gov

Registry ID
ClinicalTrials.gov ID
Registry record
Open registry record

Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design

  1. Overall Survival (OS) in Participants With Positive Programmed Cell Death-Ligand 1 (PD-L1) Expression (≥1%Tumor Cells) and in all Randomized Participants.

    Timeframe: Up to 68 months

    OS is defined as the time from the date of randomization to the date of death from any cause.

  1. Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Timeframe: Upt to 50 months

    PFS is defined as the time from the date of randomization until disease progression (PD) or death from any cause, whichever comes first.

  2. Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1

    Timeframe: Up to 50 Months

    ORR is defined as the proportion of participants who have achieved a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later.

  3. Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1

    Timeframe: Up to 50 Months

    DOR is defined as the time from the first response (CR or PR), to the first documented PD or death from any cause, whichever comes first.

  4. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

    Timeframe: First dose date up to 50 months plus 30 days

  5. Percentage of Participants Experiencing Clinical Laboratory Abnormalities

    Timeframe: First dose date up to 50 months plus 30 days

  6. Time to First Symptom Deterioration in Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score

    Timeframe: Baseline, Up to 50 Months

    The NSCLC-SAQ is a patient reported outcome measure with seven items assessing five symptom concepts of NSCLC: cough, pain, dyspnea, fatigue, and appetite. Each item is rated using a five-point verbal rating scale from "No \<symptom\> At All" to "Very severe \<symptom\>" or from "Never to Always," corresponding to a score of 0 to 4. The sum of all 5 domain scores will be computed, if any scores are missing, a total score will not be computed. The total score ranges between 0 and 20 with higher scores indicating more severe symptoms.

Sources for outcomes

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  • Life expectancy ≥ 3 months.

  • Pathologically documented NSCLC that meets both of the criteria below:

    • Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition).
    • Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations.
  • Have no actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies.

  • Have not received prior systemic treatment for metastatic NSCLC.

  • Measurable disease per RECIST v1.1 criteria by investigator assessment.

  • Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.

  • Have adequate organ functions.

Key Exclusion Criteria:

  • Have mixed small-cell lung cancer (SCLC) and NSCLC histology.
  • Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period.
  • Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint.
  • Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
  • Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
  • Have an active autoimmune disease that required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
  • Are receiving chronic systemic steroids.
  • Have significant third-space fluid retention.
  • Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment.
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has had an allogenic tissue/solid organ transplant.
  • Have received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
  • Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sources for eligibility

  • Innovative Clinical Research InstituteWhittier, United States
  • George Washington Medical Faculty AssociatesWashington D.C., United States
  • Moffitt Cancer CenterTampa, United States
  • Illinois Cancer CarePeoria, United States
  • Messino Cancer CentersAsheville, United States
  • Oncology Hematology Care, Inc.Cincinnati, United States
  • Hematology & Oncology AssociatesEugene, United States
  • AHN Allegheny General HospitalPittsburgh, United States
  • Texas Oncology - AustinAustin, United States
  • Oncology and Hematology Associates of Southwest Virginia, IncBlacksburg, United States
  • Northwest Cancer Specialists, PCVancouver, United States
  • Investigaciones CORI S.R.L.Capital, Argentina
  • Centro Médico Privado Centro de Especialidades Médicas Ambulatorias e Investigación ClínicaCardoba, Argentina
  • Sanatorio AllendeCórdoba, Argentina
  • Sanatorio Britanico de RosarioRosario, Argentina
  • Sanatorio Parque de RosarioRosario, Argentina
  • Hospital Provincial del CentenarioRosario, Argentina
  • Instituto Medico de la Fundacion Estudios ClinicosRosario, Argentina
  • Clínica ViedmaViedma, Argentina
  • Ordensklinikum Linz GmbH, ElisabethinenLinz, Austria
  • Krankenhaus Nord - Klinik FloridsdorfVienna, Austria
  • Klinikum Wels-GrieskirchenWels, Austria
  • Algemeen Ziekenhuis Sint-LucasAalst, Belgium
  • Grand Hopital de Charleroi asbl (GHdC)Charleroi, Belgium
  • AZ Sint-MaartenMechelen, Belgium

And 161 more, listed on the interactive page.

Sources for sites

Other registry identifiers

  • 2022-000578-25
Sources for references

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