A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer

NCT03846310 | Completed Phase 1 FDA Drug

• 1 other identifier: ARC-4 (AB928CSP0004)
• Study Type: interventional
• Target: 77
• Locations: 4 countries
• Sites: 22

Brief Summary

This is a Phase 1/1b, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and clinical activity of etrumadenant (AB928) in combination with carboplatin and pemetrexed, with or without an anti-PD-1 antibody (pembrolizumab or zimberelimab), in participants with non-squamous Non-Small Cell Lung Cancer (NSCLC).

Conditions

Non Small Cell Lung Cancer Metastatic; Non Small Cell Lung Cancer; Nonsquamous Nonsmall Cell Neoplasm of Lung; Sensitizing EGFR Gene Mutation

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with Adverse Events

  From first study treatment administration until up to 90 days after the last dose (Approximately 1 year)

• Percentage of participants who experience a Dose Limiting Toxicity

  From first study treatment administration through Day 21

Secondary Outcomes (7)

• Percentage of participants with anti-drug antibodies to zimberelimab

  Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).

• Plasma concentration of etrumadenant

  Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).

• Serum concentration of zimberelimab

  Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).

• Progression Free Survival (PFS)

  From start of treatment up to the first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)

• Duration of Response

  From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)

Study Arms (4)

Dose Escalation Arm A

EXPERIMENTAL

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The RDE of etrumadenant will be determined in this part with escalating doses of etrumadenant in combination with standard doses of carboplatin/pemetrexed chemotherapy regimen in participants with Non-Small Cell Lung Cancer.

Drug: Etrumadenant; Drug: Carboplatin; Drug: Pemetrexed

Dose Escalation Arm B

EXPERIMENTAL

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The RDE of etrumadenant will be determined in this part with escalating doses of etrumadenant in combination with standard doses of carboplatin/pemetrexed chemotherapy regimen and pembrolizumab in participants with Non-Small Cell Lung Cancer.

Drug: Etrumadenant; Drug: Carboplatin; Drug: Pemetrexed; Drug: Pembrolizumab

Dose Expansion Arm 1

EXPERIMENTAL

Zimberelimab will be administered in combination with standard carboplatin and pemetrexed chemotherapy regimen in participants with Non-Small Cell Lung Cancer harboring a sensitizing EGFR mutation.

Drug: Zimberelimab; Drug: Carboplatin; Drug: Pemetrexed

Dose Expansion Arm 2

EXPERIMENTAL

The etrumadenant at RDE determined from the dose escalation phase will be administered in combination with standard carboplatin and pemetrexed chemotherapy regimen and zimberelimab in participants with Non-Small Cell Lung Cancer harboring a sensitizing EGFR mutation.

Drug: Etrumadenant; Drug: Zimberelimab; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Etrumadenant DRUG

Etrumadenant is an A2aR and A2bR antagonist

Also known as: AB928

Dose Escalation Arm A; Dose Escalation Arm B; Dose Expansion Arm 2

Zimberelimab DRUG

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

Also known as: AB122

Dose Expansion Arm 1; Dose Expansion Arm 2

Carboplatin DRUG

Carboplatin administered as part of standard chemotherapy regimen

Dose Escalation Arm A; Dose Escalation Arm B; Dose Expansion Arm 1; Dose Expansion Arm 2

Pemetrexed DRUG

Pemetrexed administered as part of standard chemotherapy regimen

Dose Escalation Arm A; Dose Escalation Arm B; Dose Expansion Arm 1; Dose Expansion Arm 2

Pembrolizumab DRUG

Pembrolizumab is a humanized anti-PD-1 monoclonal antibody

Dose Escalation Arm B

Eligibility Criteria

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

You may qualify if:

• Male or female participants; age ≥ 18 years
• Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced, or recurrent with progression
• Arm A participants must fulfill one of the following:
• Participant has a genetic alteration (mutation or rearrangement) and has received all available targeted therapy. Previous treatment with chemotherapy or PD-1/-L1 therapy is not allowed.
• Participant has not received any therapy for the disease under study and standard therapy is refused.
• Participant has progressed on PD-1/-L1 therapy (monotherapy or combination regimen). Previous treatment with chemotherapy is not allowed.
• Participant has progressed on PD-1/-L1 therapy (monotherapy or combination regimen) and has received less than 4 cycles of carboplatin/pemetrexed and further chemotherapy is appropriate.
• Participant has received any number of prior treatments and is without alternative or curative therapy.
• Arm B participants must fulfill one of the following:
• Participant has a genetic alteration (mutation or rearrangement) and has received all available targeted therapy. Previous treatment with chemotherapy or PD-1/-L1 therapy is not allowed.
• Participant has not received any therapy for the disease under study and standard therapy is refused.
• Participant has received any number of prior treatments and is without alternative or curative therapy.
• Arm 1 and Arm 2 participants must have a sensitizing epidermal growth factor receptor (EGFR) mutation with disease progression or treatment intolerance after one or more approved TKIs. Previous treatment with chemotherapy or PD-1/L-1 therapy is not allowed.
• No TKI therapy within 5 days of Cycle 1 Day 1
• The last dose of previous investigational therapy is at least 4 weeks or 5 half-lives prior to Cycle 1 Day 1.

You may not qualify if:

• Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational product
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 30 days after the last dose of etrumadenant, 90 days after the last dose of zimberelimab or pembrolizumab, or 6 months after the last dose of pemetrexed, whichever is longer
• 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 use of an adenosine pathway targeting agent
• Due to potential for drug-drug interactions with etrumadenant, participants must not have had:
• Treatment with breast cancer resistance protein substrates or P-glycoprotein with a narrow therapeutic window, administered orally within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
• Treatment with known strong cytochrome P450 3A4 (CYP3A4) inducers and strong CYP3A4 inhibitors within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

Sponsors & Collaborators

• Arcus Biosciences, Inc.: lead
• Gilead Sciences: collaborator

Study Sites (22)

Arizona Cancer Research Center (ACRC)

Tucson, Arizona, 85715, United States

Location

SCRI Florida Cancer Specialists - South

Fort Myers, Florida, 33901, United States

Location

SCRI Florida Cancer Specialists - North

Tavares, Florida, 33705, United States

Location

SCRI Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

USO Texas Oncology - Dallas (Baylor Charles A. Sammons Cancer Center)

Dallas, Texas, 75246, United States

Location

USO Virginia Cancer Specialist

Fairfax, Virginia, 22031, United States

Location

USO Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Medical Oncology Associates/Summit Cancer Center

Spokane, Washington, 99208, United States

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

The Catholic University of Korea St. Vincent Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

Location

Bundang CHA Medical Center

Seongnam-si, 13496, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

Location

Asan Medical Centre

Seoul, 5505, South Korea

Location

Seoul St. Mary's Hospital

Seoul, 6591, South Korea

Location

Seoul National University Hospital

Suwon, 3080, South Korea

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Taipei Medical University - Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

Chi Mei Hospital, Liouying

Tainan, 73657, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Tri Service General Hospital

Taipei, 11490, Taiwan

Location

Related Links

• ARC-4 - Public website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

zimberelimab; Carboplatin; Pemetrexed; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Medical Director

  Arcus Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 19, 2019
• Study Start: April 1, 2019
• Primary Completion: November 18, 2024
• Study Completion: November 18, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

SG (2); KR (7); TW (5); US (8)