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A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03846310
Recruitment Status : Recruiting
First Posted : February 19, 2019
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

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 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).

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Metastatic Non Small Cell Lung Cancer Nonsquamous Nonsmall Cell Neoplasm of Lung Sensitizing EGFR Gene Mutation Drug: AB928 Drug: Zimberelimab Drug: Carboplatin Drug: Pemetrexed Drug: Pembrolizumab Phase 1

Detailed Description:

In the dose-escalation phase, escalating doses of AB928 in combination with carboplatin and pemetrexed at standard doses (Arm A), and AB928 in combination with carboplatin, pemetrexed and pembrolizumab (Arm B), may be assessed in participants with advanced NSCLC. Eligible participants will receive oral administration of AB928 as well as IV infused carboplatin, pemetrexed, with or without pembrolizumab in this phase. The recommended dose for expansion (RDE) of AB928 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 AB928 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+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 : April 1, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


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 AB928 will be determined in this part with escalating doses of AB928 in combination with standard doses of carboplatin/pemetrexed chemotherapy regimen in participants with Non-Small Cell Lung Cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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 AB928 will be determined in this part with escalating doses of AB928 in combination with standard doses of carboplatin/pemetrexed chemotherapy regimen and pembrolizumab in participants with Non-Small Cell Lung Cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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 Name: 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 AB928 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: AB928
AB928 is an A2aR and A2bR antagonist

Drug: Zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclonal antibody
Other Name: AB122

Drug: Carboplatin
Carboplatin administered as part of standard chemotherapy regimen

Drug: Pemetrexed
Pemetrexed administered as part of standard chemotherapy regimen




Primary Outcome Measures :
  1. Percentage of participants with Adverse Events [ Time Frame: 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 [ Time Frame: From first study treatment administration through Day 21 ]

Secondary Outcome Measures :
  1. Percentage of participants with anti-drug antibodies to zimberelimab [ Time Frame: 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 AB928 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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. Overall Survival (OS) [ Time Frame: From study start of treatment up to death from any cause (up to approximately 3-5 years) ]
  6. Duration of Response [ Time Frame: 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) ]
  7. Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  8. Percentage of participants with Objective Response [ Time Frame: 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 AB928, 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 AB928, 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 #A4 (CYP344) inducers and strong CYP3A4 inhibitors within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03846310


Contacts
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Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
Show Show 36 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
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Study Director: Medical Director Arcus Biosciences, Inc.
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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03846310    
Other Study ID Numbers: AB928CSP0004
First Posted: February 19, 2019    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors