A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
1 other identifier
interventional
48
2 countries
15
Brief Summary
This is a Phase 1, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity of etrumadenant (AB928) in combination with zimberelimab (AB122) (an anti-PD-1 antibody) in participants with advanced malignancies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 nonsmall-cell-lung-cancer
Started Jul 2018
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2018
CompletedStudy Start
First participant enrolled
July 24, 2018
CompletedFirst Posted
Study publicly available on registry
August 14, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 18, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 3, 2021
CompletedMay 24, 2024
May 1, 2024
3.1 years
July 17, 2018
May 23, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of participants with Adverse Events
Safety will be assessed by monitoring adverse events and clinically relevant changes in Eastern Cooperative Oncology Group (ECOG) performance status, 12 lead Electrocardiogram (ECG), vital signs, physical examination and clinical laboratory results.
From first dose date to 90 days after the last dose (approximately 3 years)
Percentage of participants who experience a Dose Limiting Toxicity
From first study treatment administration through Day 28
Secondary Outcomes (10)
Etrumadenant Peak Serum Concentration: Cmax
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Zimberelimab Peak Serum Concentration: Cmax
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Etrumadenant Time of Peak Concentration: Tmax
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Zimberelimab Time of Peak Concentration: Tmax
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Percentage of participants with anti-drug antibodies to zimberelimab
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), at end of treatment, and 30 and 90 days post last dose (approximately 7 months)
- +5 more secondary outcomes
Study Arms (3)
Dose Escalation
EXPERIMENTAL3+3 design, including a DLT evaluation period. Etrumadenant RP2D will be determined in this part with escalating doses of oral etrumadenant in combination with a fixed dose of IV zimberelimab.
Dose Expansion-advanced clear-cell RCC
EXPERIMENTALEtrumadenant at RP2D + zimberelimab
Dose Expansion-mCRPC
EXPERIMENTALEtrumadenant at RP2D + zimberelimab
Interventions
Etrumadenant is an A2aR and A2bR antagonist.
Zimberelimab is a fully human anti-PD-1 monoclonal antibody.
Eligibility Criteria
You may qualify if:
- Male or female participants ≥ 18 years
- Must have at least 1 measurable lesion per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Must have received standard of care, including potentially curative available therapies or interventions.
- Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained. Biopsy must not put participant at undue risk and the procedure must not be more invasive than a core biopsy.
- Adequate organ and marrow function
- Dose escalation only:
- Pathologically confirmed non-small cell lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, breast cancer, colorectal cancer, melanoma, bladder cancer, ovarian cancer, endometrial cancer, Merkel cell carcinoma, or gastroesophageal cancer that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists or standard therapy is not considered appropriate by the participant and treating physician (reason must be documented in medical records).
- Dose expansion only:
- Participants with advanced clear-cell RCC or mCRPC.9. Clear-cell RCC participants may have received up to 2 prior lines of therapy, one of which must have included an anti-PD-(L)1 based therapy and must not have progressed within 16 weeks during an anti-PD-(L)1 therapy.
- mCRPC participants must have progressed during or following treatment with an androgen synthesis inhibitor, and have also had one prior line of a taxane-containing regimen or the physician and participant consider the taxane-containing regimen to be inappropriate.
- mCRPC participants must be naive to any immunotherapy (including but not limited to anti-PD-(L)1 or anti-CTLA-4 antagonists, sipuleucel-T, etc.).
You may not qualify if:
- Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product.
- Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous (eg, interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs, or concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic or absorbable topical corticosteroids.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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 90 days after the last dose of etrumadenant in combination with zimberelimab.
- Any active or documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
- Prior malignancy active within the previous year 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.
- Dose escalation: Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other immune checkpoint inhibitor or agonist as a monotherapy or in combination;
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Scottsdale Healthcare Hospitals dba HonorHealth
Scottsdale, Arizona, 85258, United States
University of California, Los Angeles
Los Angeles, California, 90024, United States
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
Rocky Mountain Cancer Centers (Midtown)
Denver, Colorado, 80218, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
QUEST Research Institute
Royal Oak, Michigan, 48073, United States
Carolina BioOncology Institute
Huntersville, North Carolina, 28078, United States
Prisma Health
Greenville, South Carolina, 29605, United States
Texas Oncology, P.A. - Fort Worth Cancer Center
Fort Worth, Texas, 76104, United States
Texas Oncology, P.A. - San Antonio Medical Center
San Antonio, Texas, 78240, United States
Texas Oncology, P.A. - Tyler
Tyler, Texas, 75702, United States
Medical Oncology Associates dba Summit Cancer Centers
Spokane, Washington, 99208, United States
St. George Private Hospital
Kogarah, New South Wales, 2217, Australia
Gallipoli Medical Research Foundation
Greenslopes, Queensland, 4120, Australia
Cabrini Health Limited
Malvern, 3144, Australia
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Arcus Biosciences, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2018
First Posted
August 14, 2018
Study Start
July 24, 2018
Primary Completion
August 18, 2021
Study Completion
September 3, 2021
Last Updated
May 24, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan \[SAP\], Clinical Study Report \[CSR\]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. For more information, please visit our website.