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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 : August 5, 2019
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 (PD), and clinical activity of AB928 in combination with carboplatin/pemetrexed with or without pembrolizumab and AB122 monotherapy 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 Drug: AB928 Drug: AB122 Drug: Carboplatin Drug: Pemetrexed Drug: Pembrolizumab Phase 1

Detailed Description:

Dose escalation of AB928 in combination with carboplatin/pemetrexed and AB928 in combination with carboplatin/pemetrexed plus pembrolizumab at standard doses will be assessed in participants with advanced metastatic non-squamous Non-Small Cell Lung Cancer. In this dose escalation combination study, participants will receive oral administration of AB928 as well as IV infused carboplatin/pemetrexed with or without pembrolizumab.

Dose expansion of AB928 in combination with carboplatin/pemetrexed and AB928 in combination with carboplatin/pemetrexed plus pembrolizumab at standard doses may be assessed in participants with advanced metastatic non-squamous Non-Small Cell Lung Cancer. The dose of AB928 used will be determined based on the findings from the dose escalation phase.

Concurrently, AB122 monotherapy will be assessed in participants with advanced non-squamous Non-Small Cell Lung Cancer.

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 : 128 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

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Dose Escalation Arm A
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB829 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 dose expansion dose level will be determined in this part with escalating doses of AB829 in combination 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
The dose administered in expansion will be determined during dose escalation. AB928 will be administered in combination with standard 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 Expansion Arm 2
The dose administered in expansion will be determined during dose escalation. AB928 will be administered in combination with standard 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: Arm 3
AB122 will be administered as monotherapy to participants with Non-Small Cell Lung Cancer.
Drug: AB122
AB122 is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1




Primary Outcome Measures :
  1. Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 [ Time Frame: From first dose date to 90 days after the last dose (Approximately 1 year) ]
    Number of Participants Treated with AB928 in Combination with carboplatin/pemetrexed with or without pembrolizumb or AB122 monotherapy with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0


Secondary Outcome Measures :
  1. AB928 and AB122 Pharmacokinetic (PK) Concentration: Cmax [ 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 6 months). Each Cycle is 28 Days. ]
    Measured using the area under the concentration-time curve from serum plasma collection and analysis

  2. AB928 and AB122 Pharmacokinetic (PK) Concentration: Tmax [ 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 6 months). Each Cycle is 28 Days. ]
    Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis

  3. Clinical Activity of AB928 combination therapy [ Time Frame: Recorded at Baseline (Screening), every 9 weeks until progression (approximately 6 months in total) ]
    Tumor assessments over time will be measured using RECIST v1.1.

  4. Clinical Activity of AB122 monotherapy [ Time Frame: Recorded at Baseline (Screening), every 8 weeks until progression (approximately 6 months in total) ]
    Tumor assessments over time will be measured using RECIST v1.1.

  5. AB928 and AB122 Receptor Occupancy [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days post last dose (in total approximately 6 months). Each Cycle is 28 Days. ]
    Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

  6. AB928 and AB122 Immunophenotyping [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days post last dose (in total approximately 6 months). Each Cycle is 28 Days. ]
    Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

  7. AB928 and AB122 Gene Expression [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days post last dose (in total approximately 6 months). Each Cycle is 28 days. ]
    Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

  8. AB928 and AB122 Cytokines [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days post last dose (in total approximately 6 months). Each Cycle is 28 days. ]
    Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples



Information from the National Library of Medicine

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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:

  1. Male or female participants; age ≥ 18 years
  2. Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced, or recurrent with progression.
  3. Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  5. Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained.
  6. Prior chemotherapy or immunotherapy or biologic agents must have been completed at least 4 weeks before IP administration.
  7. Adequate organ and marrow function

Exclusion Criteria:

  1. Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational product.
  2. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product(s) hazardous
  3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  4. 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 investigational product for non-PD-1-containing regimens and through 90 days after the last dose of investigational products for PD-1-containing regimens.
  5. 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.
  6. 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.
  7. Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks prior to Day 1 or has not recovered (ie, ≤ Grade 1 or baseline) from AEs due to a previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy and other AEs considered not clinically significant by the Medical Monitor and Investigator.
  8. Prior use of an adenosine pathway targeting agent.
  9. Participants who are eligible for potentially curative available therapies or interventions.
  10. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before investigational product administration.

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
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United States, Arizona
Tucson, Arizona Not yet recruiting
Tucson, Arizona, United States, 85715
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
United States, Colorado
Denver, Colorado Recruiting
Denver, Colorado, United States, 80218
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
United States, Maryland
Rockville, Maryland Recruiting
Rockville, Maryland, United States, 20850
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
United States, Nevada
Las Vegas, Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
United States, Texas
Austin, Texas Recruiting
Austin, Texas, United States, 78705
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Dallas, Texas Recruiting
Dallas, Texas, United States, 75246
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Fort Worth, Texas Recruiting
Fort Worth, Texas, United States, 76104
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
San Antonio, Texas Recruiting
San Antonio, Texas, United States, 78217
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
San Antonio, Texas Recruiting
San Antonio, Texas, United States, 78240
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Tyler, Texas Recruiting
Tyler, Texas, United States, 75702
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
United States, Virginia
Fairfax, Virginia Recruiting
Fairfax, Virginia, United States, 22031
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Norfolk, Virginia Recruiting
Norfolk, Virginia, United States, 23502
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
United States, Washington
Spokane, Washington Recruiting
Spokane, Washington, United States, 99208
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Tacoma, Washington Recruiting
Tacoma, Washington, United States, 98405
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
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     History of Changes
Other Study ID Numbers: AB928CSP0004
First Posted: February 19, 2019    Key Record Dates
Last Update Posted: August 5, 2019
Last Verified: August 2019

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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