A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer
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| ClinicalTrials.gov Identifier: NCT03846310 |
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Recruitment Status :
Recruiting
First Posted : February 19, 2019
Last Update Posted : January 20, 2021
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Sponsor:
Arcus Biosciences, Inc.
Information provided by (Responsible Party):
Arcus Biosciences, Inc.
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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).
| 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: Etrumadenant Drug: Zimberelimab Drug: Carboplatin Drug: Pemetrexed Drug: Pembrolizumab | Phase 1 |
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 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
MedlinePlus Genetics related topics:
Lung cancer
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
Other Name: AB928 Drug: Carboplatin Carboplatin administered as part of standard chemotherapy regimen Drug: Pemetrexed Pemetrexed administered as part of standard chemotherapy regimen |
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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.
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
Other Name: 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 |
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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.
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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 |
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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.
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Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
Other Name: AB928 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 :
- 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) ]
- Percentage of participants who experience a Dose Limiting Toxicity [ Time Frame: From first study treatment administration through Day 21 ]
Secondary Outcome Measures :
- 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). ]
- Plasma concentration of etrumadenant [ 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). ]
- 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). ]
- 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) ]
- Overall Survival (OS) [ Time Frame: From study start of treatment up to death from any cause (up to approximately 3-5 years) ]
- 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) ]
- 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) ]
- 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
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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
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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.
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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
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
| Contact: Medical Director | 510-694-6200 | ClinicalTrialInquiry@arcusbio.com |
Locations
Show 38 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
| Study Director: | Medical Director | Arcus Biosciences, Inc. |
| 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: | January 20, 2021 |
| Last Verified: | January 2021 |
| 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 |