A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer

Sponsor
Arcus Biosciences, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03846310
Collaborator
(none)
77
37
4
42
2.1
0

Study Details

Study Description

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).

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
77 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
3+3 dose escalation3+3 dose escalation
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Lung Cancer
Actual Study Start Date :
Apr 1, 2019
Anticipated Primary Completion Date :
Aug 1, 2022
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
Other Names:
  • AB928
  • Drug: Carboplatin
    Carboplatin administered as part of standard chemotherapy regimen

    Drug: Pemetrexed
    Pemetrexed administered as part of standard chemotherapy regimen

    Experimental: 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.

    Drug: Etrumadenant
    Etrumadenant is an A2aR and A2bR antagonist
    Other Names:
  • AB928
  • Drug: Carboplatin
    Carboplatin administered as part of standard chemotherapy regimen

    Drug: Pemetrexed
    Pemetrexed administered as part of standard chemotherapy regimen

    Drug: Pembrolizumab
    Pembrolizumab is a humanized anti-PD-1 monoclonal antibody

    Experimental: 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.

    Drug: Zimberelimab
    Zimberelimab is a fully human anti-PD-1 monoclonal antibody
    Other Names:
  • AB122
  • Drug: Carboplatin
    Carboplatin administered as part of standard chemotherapy regimen

    Drug: Pemetrexed
    Pemetrexed administered as part of standard chemotherapy regimen

    Experimental: 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.

    Drug: Etrumadenant
    Etrumadenant is an A2aR and A2bR antagonist
    Other Names:
  • AB928
  • Drug: Zimberelimab
    Zimberelimab is a fully human anti-PD-1 monoclonal antibody
    Other Names:
  • AB122
  • Drug: Carboplatin
    Carboplatin administered as part of standard chemotherapy regimen

    Drug: Pemetrexed
    Pemetrexed administered as part of standard chemotherapy regimen

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of participants with Adverse Events [From first study treatment administration until up to 90 days after the last dose (Approximately 1 year)]

    2. Percentage of participants who experience a Dose Limiting Toxicity [From first study treatment administration through Day 21]

    Secondary Outcome Measures

    1. 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).]

    2. 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).]

    3. 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).]

    4. 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)]

    5. 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)]

    6. Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months [From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)]

    7. Percentage of participants with Objective Response [From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 3-5 years)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Clinical Research Center Tucson Arizona United States 85715
    2 Rocky Mountain Cancer Center Denver Colorado United States 80218
    3 Florida Cancer Specialists - South Fort Myers Florida United States 33901
    4 Florida Cancer Specialists & Research Institute Tavares Florida United States 33705
    5 Maryland Oncology Hematology, P.A. Rockville Maryland United States 20850
    6 HCA Midwest Health Kansas City Kansas City Missouri United States 64132
    7 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    8 Columbia University Medical Center-Herbert Irving Pavilion New York New York United States 10032
    9 SCRI - University of Oklahoma Norman Oklahoma United States 73019
    10 Tennessee Oncology - Chattanooga Chattanooga Tennessee United States 37404
    11 Tennessee Oncology Nashville Tennessee United States 37203
    12 Texas Oncology, P.A. - Austin (Midtown) Austin Texas United States 78705
    13 Texas Oncology - Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    14 Texas Oncology Fort Worth Texas United States 76104
    15 Texas Oncology, P.A. - San Antonio Northeast San Antonio Texas United States 78217
    16 Texas Oncology - Tyler Tyler Texas United States 75702
    17 Virginia Cancer Specialists Fairfax Virginia United States 22031
    18 Virginia Oncology Associates Norfolk Virginia United States 23502
    19 Medical Oncology Associates, PS (dba Summit Cancer Centers) Spokane Washington United States 99208
    20 Northwest Medical Specialties, PLLC Tacoma Washington United States 98405
    21 Queen Mary Hospital (The University of Hong Kong) Hong Kong Hong Kong 999077
    22 Prince of Wales Hospital (The Chinese University of Hong Kong) Sha Tin Hong Kong 999077
    23 St Vincent Hospital of the Catholic University of Korea Suwon-si Gyeonggi-do Korea, Republic of 16247
    24 Chungbuk National University Hospital Cheongju-si Korea, Republic of 28644
    25 Chonnam National University Hwasun Hospital Hwasun Korea, Republic of 58128
    26 CHA Bundang Medical Center, CHA University Seongnam-si Korea, Republic of 13496
    27 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    28 Asan Medical Centre Seoul Korea, Republic of 05505
    29 Seoul St. Mary's Hospital, The Catholic University of Korea Seoul Korea, Republic of 06591
    30 Seoul National University Hospital Suwon Korea, Republic of 03080
    31 National University Hospital Singapore Singapore 119228
    32 National Cancer Centre Singapore Singapore Singapore 169610
    33 Changhua Christian Hospital Changhua Taiwan 500
    34 Taipei Medical University - Shuang Ho Hospital New Taipei City Taiwan 23561
    35 Chi Mei Hospital, Liouying Tainan City Taiwan 73657
    36 National Taiwan University Hospital Taipei City Taiwan 10002
    37 Tri-Service General Hospital Taipei Taiwan 11490

    Sponsors and Collaborators

    • Arcus Biosciences, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Arcus Biosciences, Inc.
    ClinicalTrials.gov Identifier:
    NCT03846310
    Other Study ID Numbers:
    • AB928CSP0004
    First Posted:
    Feb 19, 2019
    Last Update Posted:
    May 3, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 3, 2022