A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies

Sponsor
Arcus Biosciences, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03629756
Collaborator
(none)
48
Enrollment
15
Locations
3
Arms
37.4
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Detailed Description

In the dose-escalation phase, escalating doses of etrumadenant in combination with zimberelimab will be assessed in participants with advanced malignancies. Eligible participants will receive oral administration of etrumadenant as well as IV infusion of zimberelimab. The recommended Phase 2 dose (RP2D) of etrumadenant will be determined upon completion of the dose-escalation phase.

In the dose-expansion phase, etrumadenant at RP2D in combination with zimberelimab may be assessed in participants with advanced clear-cell renal cell carcinoma (RCC) or metastatic castrate-resistant adenocarcinoma of the prostate (mCRPC).

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 :
48 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
3+3 Dose escalation design.3+3 Dose escalation design.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Actual Study Start Date :
Jul 24, 2018
Actual Primary Completion Date :
Aug 18, 2021
Actual Study Completion Date :
Sep 3, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dose Escalation

3+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.

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
  • Experimental: Dose Expansion-advanced clear-cell RCC

    Etrumadenant at RP2D + zimberelimab

    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
  • Experimental: Dose Expansion-mCRPC

    Etrumadenant at RP2D + zimberelimab

    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
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of participants with Adverse Events [From first dose date to 90 days after the last dose (approximately 3 years)]

      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.

    2. Percentage of participants who experience a Dose Limiting Toxicity [From first study treatment administration through Day 28]

    Secondary Outcome Measures

    1. 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)]

    2. 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)]

    3. 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)]

    4. 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)]

    5. 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)]

    6. Progression Free Survival (PFS) [From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)]

      PFS as determined by Investigator according to Prostate Cancer Working Group 3 (PCWG3) for prostate adenocarcinoma and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for all other tumor types

    7. Overall Survival (OS) [From study start of treatment up to death from any cause (approximately 1-3 years)]

      OS as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    8. Duration of Response (DOR) [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 (approximately 1-3 years)]

      DOR as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    9. Percentage of Participants with Disease Control [From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)]

      Disease Control (complete response, partial response, or stable disease) for >6 months as determined by the Investigator per PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    10. Percentage of participants with Objective Response [From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)]

      Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male or female participants ≥ 18 years

    2. Must have at least 1 measurable lesion per RECIST v1.1.

    3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

    4. Must have received standard of care, including potentially curative available therapies or interventions.

    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. Biopsy must not put participant at undue risk and the procedure must not be more invasive than a core biopsy.

    6. Adequate organ and marrow function

    Dose escalation only:
    1. 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:
    1. 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.

    2. 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.

    3. 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.).

    Exclusion Criteria:
    1. Use of any live vaccines against infectious diseases (eg, influenza, varicella) 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 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.

    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 90 days after the last dose of etrumadenant in combination with zimberelimab.

    5. 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.

    6. 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.

    7. 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;

    8. 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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Scottsdale Healthcare Hospitals dba HonorHealthScottsdaleArizonaUnited States85258
    2University of California, Los AngelesLos AngelesCaliforniaUnited States90024
    3The Angeles Clinic and Research InstituteLos AngelesCaliforniaUnited States90025
    4Rocky Mountain Cancer Centers (Midtown)DenverColoradoUnited States80218
    5University of MichiganAnn ArborMichiganUnited States48109
    6QUEST Research InstituteRoyal OakMichiganUnited States48073
    7Carolina BioOncology InstituteHuntersvilleNorth CarolinaUnited States28078
    8Prisma HealthGreenvilleSouth CarolinaUnited States29605
    9Texas Oncology, P.A. - Fort Worth Cancer CenterFort WorthTexasUnited States76104
    10Texas Oncology, P.A. - San Antonio Medical CenterSan AntonioTexasUnited States78240
    11Texas Oncology, P.A. - TylerTylerTexasUnited States75702
    12Medical Oncology Associates dba Summit Cancer CentersSpokaneWashingtonUnited States99208
    13St. George Private HospitalKogarahNew South WalesAustralia2217
    14Gallipoli Medical Research FoundationGreenslopesQueenslandAustralia4120
    15Cabrini Health LimitedMalvernAustralia3144

    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:
    NCT03629756
    Other Study ID Numbers:
    • AB928CSP0005
    First Posted:
    Aug 14, 2018
    Last Update Posted:
    Apr 1, 2022
    Last Verified:
    Mar 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 Apr 1, 2022