Zimberelimab and domvanalimab in combination with chemotherapy versus pembrolizumab with chemotherapy in patients with untreated metastatic non-small cell lung cancer
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.
Source : Import from center
RECRUITMENT
Participant profile
Age limits
minimum: 18 years old
Participants gender(s)
ALL
Source : Import from center
Medical condition (targeted specialty)
Research domain
Non-small Cell Lung Cancer
Selection criterias
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.
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Data not available
Unknown
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Data not available
Unknown
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Pembrolizumab (PEMBRO) + Chemotherapy
Recruitment status
unknown
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Zimberelimab (ZIM) + Chemotherapy
Recruitment status
unknown
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Current data since :
January 29, 2026 19:00
LOCATIONS AND CONTACTS
Main location
innovative clinical research institute
WHITTIER, CALIFORNIA, UNITED STATES
Local recruitment
—
CLOSED
Locations in Quebec
Santé Québec Bas-Saint-Laurent
RIMOUSKI, QUÉBEC, CANADA
Local recruitment
—
CLOSED
Santé Québec Laurentides
SAINT-JÉRÔME, QUEBEC, CANADA
(450) 431-6571
Local recruitment
—
CLOSED
centre integre de sante et de services sociaux de la monteregie centre
GREENFIELD PARK, QUEBEC, CANADA
Local recruitment
—
CLOSED
cisss des laurentides
QUÉBEC, CANADA
Local recruitment
—
CLOSED
Also available at: CAPITAL, BARCELONA, (BARCELONA), BARCELONA, (OTHER), BARCELONA, (CATALUNYA [CATALUÑA]), SINGAPORE, TAIPEI, (OTHER), BARCELONA, (OTHER), PAVIA, MINDEN, (NORDRHEIN-WESTFALEN), ESSEN, MONCTON, (NEW BRUNSWICK), ...
and 176 other cities.
Last modification :
January 29, 2026
Current data since :
17 Oct 08:11
Data source :
clinicaltrials.gov, Nagano
Zimberelimab and domvanalimab in combination with chemotherapy versus pembrolizumab with chemotherapy in patients with untreated metastatic non-small cell lung cancer
* 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.
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Data not available
Unknown
Pembrolizumab (PEMBRO) + Chemotherapy
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Data not available
Unknown
Zimberelimab (ZIM) + Chemotherapy
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Pembrolizumab (PEMBRO) + Chemotherapy
Recruitment status
unknown
Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Zimberelimab (ZIM) + Chemotherapy
Recruitment status
unknown
Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.
Choice of chemotherapy is dependent on histology.
* Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities.
* Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
Current data since :
January 29, 2026 19:00
Study's description
Study description
Study 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.
Source : Import from center
Locations
Locations
Participating centers
10
shown
out of
188
centers
SANTÉ QUÉBEC BAS-SAINT-LAURENT
***
Rimouski
QUÉBEC, CANADA
Local recruitment
Recruiting status:
CLOSED
click here for more information about this center
Cohorts
Santé Québec Bas-Saint-Laurent
Data not available
Current data since :
May 20, 2026 00:20
SANTÉ QUÉBEC LAURENTIDES
*
Saint-jérôme
QUEBEC, CANADA
Local recruitment
Recruiting status:
CLOSED
click here for more information about this center
Cohorts
Santé Québec Laurentides
Data not available
Current data since :
April 30, 2026 00:22
ACIBADEM MEHMET ALI AYDINLAR UNIVERSITESI ATAKENT HASTANESI
Kaakaekmece
TURKEY (TÜRKIYE)
Local recruitment
Recruiting status:
CLOSED
AHN ALLEGHENY GENERAL HOSPITAL
Pittsburgh
PENNSYLVANIA, UNITED STATES
Local recruitment
Recruiting status:
CLOSED
ALGEMEEN ZIEKENHUIS SINT-LUCAS
Aalst
BELGIUM
Local recruitment
Recruiting status:
CLOSED
AMBROISE-PARE HOSPITAL, ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Boulogne-billancourt
FRANCE
Local recruitment
Recruiting status:
CLOSED
AMPHIA ZIEKENHUIS
Breda
OTHER, NETHERLANDS
Local recruitment
Recruiting status:
CLOSED
ANKARA BILKENT SEHIR HASTANESI TIBBI ONKOLOJI KLINIGI
Ankara
ANKARA, TURKEY (TÜRKIYE)
Local recruitment
Recruiting status:
CLOSED
ASKLEPIOS KLINIKEN HAMBURG-ASKLEPIOS KLINIK BARMBEK ( SITE 1214)
Hamburg
GERMANY
Local recruitment
Recruiting status:
CLOSED
AZ SINT-MAARTEN
Mechelen
OTHER, BELGIUM
Local recruitment
Recruiting status:
CLOSED
Participating centers
Information source
Last modification :
January 29, 2026
Current data since :
17 Oct 08:11
Data source :
clinicaltrials.gov, Nagano
(450) 431-6571
