A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer

NCT ID: NCT03846310

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

77 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2024-11-18

Brief Summary

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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).

Detailed Description

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In the dose-escalation phase, escalating doses of etrumadenant in combination with carboplatin and pemetrexed at standard doses (Arm A), and etrumadenant in combination with carboplatin, pemetrexed and pembrolizumab (Arm B), may be assessed in participants with advanced NSCLC. Eligible participants will receive oral administration of etrumadenant as well as IV infused carboplatin, pemetrexed, with or without pembrolizumab in this phase. The recommended dose for expansion (RDE) of etrumadenant will be determined upon completion of the dose-escalation phase.

In the dose-expansion phase, zimberelimab in combination with carboplatin and pemetrexed (Arm 1), and etrumadenant at RDE in combination with carboplatin, pemetrexed, and zimberelimab (Arm 2) may be assessed in eligible NSCLC participants who harbor an EGFR mutation and have progressed on EGFR Tyrosine Kinase Inhibitor (TKI) treatment(s).

Overall duration of treatment will depend on how well the treatment is tolerated.

Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

3+3 dose escalation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation Arm A

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.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Carboplatin

Intervention Type DRUG

Carboplatin administered as part of standard chemotherapy regimen

Pemetrexed

Intervention Type DRUG

Pemetrexed administered as part of standard chemotherapy regimen

Dose Escalation Arm B

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.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Carboplatin

Intervention Type DRUG

Carboplatin administered as part of standard chemotherapy regimen

Pemetrexed

Intervention Type DRUG

Pemetrexed administered as part of standard chemotherapy regimen

Pembrolizumab

Intervention Type DRUG

Pembrolizumab is a humanized anti-PD-1 monoclonal antibody

Dose Expansion Arm 1

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.

Group Type EXPERIMENTAL

Zimberelimab

Intervention Type DRUG

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

Carboplatin

Intervention Type DRUG

Carboplatin administered as part of standard chemotherapy regimen

Pemetrexed

Intervention Type DRUG

Pemetrexed administered as part of standard chemotherapy regimen

Dose Expansion Arm 2

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.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist

Zimberelimab

Intervention Type DRUG

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

Carboplatin

Intervention Type DRUG

Carboplatin administered as part of standard chemotherapy regimen

Pemetrexed

Intervention Type DRUG

Pemetrexed administered as part of standard chemotherapy regimen

Interventions

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Etrumadenant

Etrumadenant is an A2aR and A2bR antagonist

Intervention Type DRUG

Zimberelimab

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

Intervention Type DRUG

Carboplatin

Carboplatin administered as part of standard chemotherapy regimen

Intervention Type DRUG

Pemetrexed

Pemetrexed administered as part of standard chemotherapy regimen

Intervention Type DRUG

Pembrolizumab

Pembrolizumab is a humanized anti-PD-1 monoclonal antibody

Intervention Type DRUG

Other Intervention Names

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AB928 AB122

Eligibility Criteria

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Inclusion Criteria

* 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.
* Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Confirm that an archival tissue sample is available and ≤ 24 months old; if not, a new biopsy of a tumor lesion should be obtained at screening
* Adequate organ and marrow function

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences, Inc.

Locations

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Arizona Cancer Research Center (ACRC)

Tucson, Arizona, United States

Site Status

SCRI Florida Cancer Specialists - South

Fort Myers, Florida, United States

Site Status

SCRI Florida Cancer Specialists - North

Tavares, Florida, United States

Site Status

SCRI Tennessee Oncology - Nashville

Nashville, Tennessee, United States

Site Status

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

Dallas, Texas, United States

Site Status

USO Virginia Cancer Specialist

Fairfax, Virginia, United States

Site Status

USO Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Medical Oncology Associates/Summit Cancer Center

Spokane, Washington, United States

Site Status

National University Hospital

Singapore, , Singapore

Site Status

National Cancer Centre Singapore

Singapore, , Singapore

Site Status

The Catholic University of Korea St. Vincent Hospital

Suwon, Gyeonggi-do, South Korea

Site Status

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status

Bundang CHA Medical Center

Seongnam-si, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Centre

Seoul, , South Korea

Site Status

Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Suwon, , South Korea

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Taipei Medical University - Shuang Ho Hospital

New Taipei City, , Taiwan

Site Status

Chi Mei Hospital, Liouying

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Tri Service General Hospital

Taipei, , Taiwan

Site Status

Countries

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Hong Kong United States Singapore South Korea Taiwan

Related Links

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Other Identifiers

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ARC-4 (AB928CSP0004)

Identifier Type: -

Identifier Source: org_study_id