Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer

NCT04791839 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202104122
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Since anti-PD1, anti-TIGIT, and A2R antagonists have complementary mechanisms of action, and the latter two have shown synergism in combination with antibodies against PD-1, othis study aims to evaluate the efficacy and tolerability of the triplet combination of zimberelimab, domvanalimab, and etrumadenant in patients with non-small cell lung cancer previously treated with immune checkpoint blockade therapy.

Conditions

Non Small Cell Lung Cancer; Non-small Cell Carcinoma; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  * Defined as the proportion of patients achieving CR or PR * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Through completion of treatment (estimated to be 9 months)

Secondary Outcomes (6)

• Number of study treatment related adverse events

  From start of treatment through 30 days after last treatment or start of next treatment (estimated to be 10 months)

• Number of discontinuations due to treatment-related adverse events

  From start of treatment through completion of treatment (estimated to be 9 months)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 5 years)

• Duration of response (DoR)

  Through completion of treatment (estimated to be 9 months)

• Disease control rate (DCR)

  Through completion of treatment (estimated to be 9 months)

Study Arms (2)

Cohort A: Zimberelimab + Domvanalimab + Etrumadenant

EXPERIMENTAL

* Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21. * Cohort A participants are those that have PD-L1 1-49%

Drug: Zimberelimab; Drug: Domvanalimab; Drug: Etrumadenant

Cohort B: Zimberelimab + Domvanalimab + Etrumadenant

EXPERIMENTAL

* Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21. * Cohort B participants are those that have PD-L1 ≥ 50%.

Drug: Zimberelimab; Drug: Domvanalimab; Drug: Etrumadenant

Interventions

Zimberelimab DRUG

Zimberelimab will be supplied by Arcus Biosciences.

Cohort A: Zimberelimab + Domvanalimab + Etrumadenant; Cohort B: Zimberelimab + Domvanalimab + Etrumadenant

Domvanalimab DRUG

Domvanalimab will be supplied by Arcus Biosciences.

Cohort A: Zimberelimab + Domvanalimab + Etrumadenant; Cohort B: Zimberelimab + Domvanalimab + Etrumadenant

Etrumadenant DRUG

Etrumadenant will be supplied by Arcus Biosciences.

Cohort A: Zimberelimab + Domvanalimab + Etrumadenant; Cohort B: Zimberelimab + Domvanalimab + Etrumadenant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic squamous or non-squamous non-small cell lung cancer.
• Previously treated with at least one line of therapy including an immune checkpoint blocker and no more than 2 prior lines in the metastatic setting.
• Documented PD-L1 expression of at least 1% by a US FDA-approved PD-L1 assay or using the clone 22C3 antibody from archival biopsy or fresh tumor tissue.
• At least one measurable lesion per RECIST 1.1 criteria.
• At least 18 years of age.
• ECOG performance status ≤ 1.
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 2.0 x IULN (except participants with Gilbert's syndrome who must have total bilirubin \< 3.0 mg/dL)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN without hepatic metastasis and ≤ 5.0 x IULN with hepatic metastasis
• Creatinine ≤2 x ULN or Creatinine clearance calculated by Cockcroft-Gault formula ≥45 ml/min
• Patients with brain or meningeal metastases are eligible provided they meet the following criteria:
• No evidence of progression by neurologic symptoms or signs for at least 4 weeks prior to first dose of study treatment

You may not qualify if:

• A history of other malignancy with the exception of:
• Malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• Carcinoma of the skin without melanomatous features.
• Patients with actionable EGFR mutation, ALK rearrangement, ROS1 fusion or RET fusion are excluded from the study.
• Currently receiving any other investigational agents or having received any investigational agents within 28 days or 5 half-lives of first dose of trial treatment.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zimberelimab, domvanalimab, etrumadenant, or other agents used in the study. Known hypersensitivity to recombinant proteins or any excipient contained in the trial formulations.
• Use of any live vaccines against infectious diseases within 28 days of first dose of trial treatment.
• Any gastrointestinal condition that would preclude the use of oral medications (e.g. difficulty swallowing, nausea, vomiting, or malabsorption).
• History of trauma or major surgery within 28 days prior to the first dose of study treatment.
• Underlying medical conditions that in the investigator's opinion will make the administration of study treatment hazardous, including but not limited to:
• Interstitial lung disease, including history of interstitial lung disease or noninfectious pneumonitis
• Active viral, bacterial or fungal infection requiring parenteral treatment within 14 days of the initiation of study treatment
• Clinically significant cardiovascular disease
• A condition that may obscure the interpretation of toxicity determination or AEs
• History of prior solid organ transplantation

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

zimberelimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Daniel Morgensztern, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 10, 2021
• Study Start: August 4, 2021
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)