Study Comparing the Combination Domvanalimab and Zimberelimab With Pembrolizumab in Untreated Locally Advanced or Metastatic PD-L1-High Non-Small Cell Lung Cancer (ARC-10)

• ClinicalTrials.gov Identifier: NCT04736173
• Recruitment Status: Active, not recruiting
• First Posted: February 3, 2021
• Last Update Posted: March 15, 2024
• Sponsor: Arcus Biosciences, Inc.
• Collaborator: Gilead Sciences
• Information provided by (Responsible Party): Arcus Biosciences, Inc.

Tracking Information

• First Submitted Date: January 29, 2021
• First Posted Date: February 3, 2021
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: February 8, 2021
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 9, 2023)

Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]

Arm D vs. Arm E

Original Primary Outcome Measures (submitted: January 29, 2021)

• Progression-free survival (PFS) [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]
  PFS as assessed by RECIST v1.1
• Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]

Current Secondary Outcome Measures (submitted: March 9, 2023)

• Progression-free Survival (PFS) [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]
  Arm D vs. Arm E - PFS as assessed by RECIST v1.1 by blinded independent central review
• Confirmed Overall Response Rate (ORR) [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]
  Arm D vs. Arm E - ORR as assessed by RECIST v1.1 by blinded independent central review
• Number of Participants With treatment-emergent adverse events [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]
  Arm D vs. Arm E
• Time to first symptom deterioration in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]
  Arm D vs. Arm E

Original Secondary Outcome Measures (submitted: January 29, 2021)

Overall response rate (ORR) [ Time Frame: From randomization until death from any cause (up to approximately 7 years) ]

ORR as assessed by RECIST v1.1

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Comparing the Combination Domvanalimab and Zimberelimab With Pembrolizumab in Untreated Locally Advanced or Metastatic PD-L1-High Non-Small Cell Lung Cancer
• Official Title: A Phase 3 Study to Evaluate Zimberelimab (AB122) Combined With AB154 in Front-Line, PD-L1-High, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
• Brief Summary: This is a phase 3 study to evaluate zimberelimab (AB122) combined with domvanalimab (AB154) compared to pembrolizumab in front-line, PD-L1-high, locally advanced or metastatic NSCLC.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non Small Cell Lung Cancer
• Nonsquamous Non Small Cell Lung Cancer
• Squamous Non Small Cell Lung Cancer
• Lung Cancer

Intervention

• Drug: Domvanalimab
  Domvanalimab is a humanized monoclonal antibody targeting human TIGIT
  Other Name: AB154
• Drug: Zimberelimab
  Zimberelimab is a fully human anti-PD-1 monoclonal antibody
  Other Name: AB122
• Drug: Carboplatin
  Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.
• Drug: Paclitaxel
  Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.
• Drug: Pemetrexed
  Participants receive carboplatin, pemetrexed, and paclitaxel at a target area under the curve.
• Drug: Pembrolizumab
  Pembrolizumab is a humanized Immunoglobulin G4 monoclonal antibody targeting the PD-1 receptor

Study Arms

• Active Comparator: Arm A - Study Part 1 (Platinum-based Chemotherapy)
  Participants will receive carboplatin, pemetrexed, and paclitaxel by intravenous (IV) infusion.
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed
• Experimental: Arm B - Study Part 1 (Zimberelimab Monotherapy)
  Participants will receive zimberelimab monotherapy by IV infusion.
  Intervention: Drug: Zimberelimab
• Active Comparator: Arm C - Study Part 1 (Domvanalimab + Zimberelimab Combination Therapy)
  Participants will receive zimberelimab in combination with AB154 by IV infusion.
  Interventions:

  • Drug: Domvanalimab
  • Drug: Zimberelimab
• Experimental: Arm D - Study Part 2 (Domvanalimab + Zimberelimab Combination Therapy)
  Participants will receive domvanalimab in combination with zimberelimab by IV infusion.
  Interventions:

  • Drug: Domvanalimab
  • Drug: Zimberelimab
• Experimental: Arm E - Study Part 2 (Pembrolizumab)
  Participants will receive pembrolizumab by IV infusion.
  Intervention: Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 13, 2024): 169
• Original Estimated Enrollment (submitted: January 29, 2021): 625
• Estimated Study Completion Date: July 1, 2027
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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:

  1. Have no evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to the first dose.
  2. 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.
  3. Carcinomatous meningitis is excluded regardless of clinical stability.

Exclusion Criteria:

• 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.

Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bangladesh, Brazil, France, Greece, Hong Kong, Korea, Republic of, Malaysia, Mexico, Peru, Philippines, Serbia, Slovakia, South Africa, Taiwan, Thailand, Turkey, United States, Vietnam
• Removed Location Countries: Belarus, Egypt, India, Russian Federation, Ukraine

Administrative Information

• NCT Number: NCT04736173
• Other Study ID Numbers: ARC-10; 2020-003562-39 ( EudraCT Number ); PHRR210222-003371 ( Other Identifier: Philippine Health Research Registry )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

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.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• URL: https://trials.arcusbio.com/our-transparency-policy

• Current Responsible Party: Arcus Biosciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Arcus Biosciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Gilead Sciences

Investigators

• Study Director: Medical Director; Arcus Biosciences, Inc.

• PRS Account: Arcus Biosciences, Inc.
• Verification Date: March 2024