NCT04736173

Brief Summary

This is a phase 2 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) in front-line, PD-L1-high, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
169

participants targeted

Target at P75+ for phase_2

Timeline
12mo left

Started Feb 2021

Longer than P75 for phase_2

Geographic Reach
10 countries

39 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Feb 2021May 2027

First Submitted

Initial submission to the registry

January 29, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 3, 2021

Completed
5 days until next milestone

Study Start

First participant enrolled

February 8, 2021

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2027

Last Updated

May 1, 2026

Status Verified

April 1, 2026

Enrollment Period

6.2 years

First QC Date

January 29, 2021

Last Update Submit

April 29, 2026

Conditions

Keywords

DomvanalimabZimberelimabNon Small Cell Lung CancerLung CancerNSCLC

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS)

    From randomization until death from any cause (up to 7 years)

Secondary Outcomes (3)

  • Overall Survival (OS)

    From randomization until death from any cause (up to 7 years)

  • Confirmed Overall Response Rate (ORR)

    From randomization until death from any cause (up to 7 years)

  • Number of Participants With treatment-emergent adverse events

    From randomization until death from any cause (up to 7 years)

Study Arms (5)

Arm A - Study Part 1 (Platinum-based Chemotherapy)

ACTIVE COMPARATOR

Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.

Drug: CarboplatinDrug: PaclitaxelDrug: Pemetrexed

Arm B - Study Part 1 (Zimberelimab Monotherapy)

EXPERIMENTAL

Participants will receive zimberelimab monotherapy by IV infusion.

Drug: Zimberelimab

Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)

EXPERIMENTAL

Participants will receive zimberelimab in combination with AB154 by IV infusion.

Drug: DomvanalimabDrug: Zimberelimab

Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)

EXPERIMENTAL

Participants will receive domvanalimab in combination with zimberelimab by IV infusion.

Drug: DomvanalimabDrug: Zimberelimab

Arm E - Study Part 2 (Pembrolizumab)

ACTIVE COMPARATOR

Participants will receive pembrolizumab by IV infusion.

Drug: Pembrolizumab

Interventions

Domvanalimab is a humanized monoclonal antibody targeting human TIGIT

Also known as: AB154
Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)

Zimberelimab is a fully human anti-PD-1 monoclonal antibody

Also known as: AB122
Arm B - Study Part 1 (Zimberelimab Monotherapy)Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)

Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.

Arm A - Study Part 1 (Platinum-based Chemotherapy)

Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.

Arm A - Study Part 1 (Platinum-based Chemotherapy)

Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.

Arm A - Study Part 1 (Platinum-based Chemotherapy)

Pembrolizumab is a humanized Immunoglobulin G4 monoclonal antibody targeting the PD-1 receptor

Arm E - Study Part 2 (Pembrolizumab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed, treatment naïve, locally advanced or metastatic (stage IIIB IV per AJCC version 8), squamous or non-squamous NSCLC with documented high PD L1 expression (TC ≥ 50%) as determined by the VENTANA SP263 IHC assay, as assessed by central laboratories).
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Must have at least 1 measurable lesion per RECIST v1.1
  • Adequate organ and marrow function
  • If a participant has brain or meningeal metastases, the participant must meet the following criteria:
  • Have no evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to the first dose.
  • Participants with previously treated brain metastases may participate provided they have stable central nervous system (CNS) disease for at least 4 weeks prior to enrollment. Stable CNS disease is defined as resolution of all neurologic symptoms to baseline, having no evidence of new or enlarging brain metastases, and not requiring use of corticosteroids for CNS disease for at least 14 days prior to the start of study treatment. Participants who have had brain metastases resected or have received whole brain radiotherapy ending at least 4 weeks (or stereotactic radiotherapy ending at least 2 weeks) prior to initiation of study treatment are permitted.
  • Carcinomatous meningitis is excluded regardless of clinical stability.

You may not qualify if:

  • Presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved by local health authority and available
  • Use of any live vaccines against infectious diseases within 28 days of first dose
  • Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
  • Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer
  • Prior treatment with any anti-PD-1, anti-PD-L1 or any other antibody targeting an immune checkpoint.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (39)

Research Site

Columbus, Georgia, 31904, United States

Location

Research Site

Kingwood, Texas, 77339, United States

Location

Research Site

Blacksburg, Virginia, 24014, United States

Location

Research Site

Hong Kong, Hong Kong

Location

Research Site

Johor Bahru, Malaysia

Location

Research Site

Kuala Lumpur, Malaysia

Location

Research Site

Kuantan, Malaysia

Location

Research Site

Kuching, Malaysia

Location

Research Site

Pulau Pinang, Malaysia

Location

Research Site

Putrajaya, Malaysia

Location

Research Site

Davao City, Philippines

Location

Research Site

Manila, Philippines

Location

Research Site

George, South Africa

Location

Research Site

Johannesburg, South Africa

Location

Research Site

Pretoria, South Africa

Location

Research Site

Daegu, South Korea

Location

Research Site

Incheon, South Korea

Location

Research Site

Jinju, South Korea

Location

Research Site

Seoul, South Korea

Location

Research Site

Suwon, South Korea

Location

Research Site

Taichung, Taiwan

Location

Research Site

Bangkok, Thailand

Location

Research Site

Changwat Sara Buri, Thailand

Location

Research Site

Chanthaburi, Thailand

Location

Research Site

Chiang Mai, Thailand

Location

Research Site

Khon Kaen, Thailand

Location

Research Site

Lampang, Thailand

Location

Research Site

Nakhon Nayok, Thailand

Location

Research Site

Nakhon Ratchasima, Thailand

Location

Research Site

Phitsanulok, Thailand

Location

Research Site

Songkhla, Thailand

Location

Research Site

Ubon Ratchathani, Thailand

Location

Research Site

Adana, Turkey (Türkiye)

Location

Research Site

Ankara, Turkey (Türkiye)

Location

Research Site

Edirne, Turkey (Türkiye)

Location

Research Site

Istanbul, Turkey (Türkiye)

Location

Research Site

Kocaeli, Turkey (Türkiye)

Location

Research Site

Hanoi, Vietnam

Location

Research Site

Huế, Vietnam

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungLung Neoplasms

Interventions

zimberelimabCarboplatinPaclitaxelPemetrexedpembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenesGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Dicarboxylic

Study Officials

  • Medical Director

    Arcus Biosciences, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 29, 2021

First Posted

February 3, 2021

Study Start

February 8, 2021

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2027

Last Updated

May 1, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan \[SAP\], Clinical Study Report \[CSR\]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. For more information, please visit our website.

Shared Documents
STUDY PROTOCOL, SAP, CSR
More information

Locations