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

NCT ID: NCT03629756

Last Updated: 2024-05-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-24

Study Completion Date

2021-09-03

Brief Summary

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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

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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.

Conditions

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Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Breast Cancer Colorectal Cancer Melanoma Bladder Cancer Ovarian Cancer Endometrial Cancer Merkel Cell Carcinoma GastroEsophageal Cancer Renal Cell Carcinoma Castration-resistant Prostate Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

3+3 Dose escalation design.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist.

Zimberelimab

Intervention Type DRUG

Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Dose Expansion-advanced clear-cell RCC

Etrumadenant at RP2D + zimberelimab

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist.

Zimberelimab

Intervention Type DRUG

Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Dose Expansion-mCRPC

Etrumadenant at RP2D + zimberelimab

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist.

Zimberelimab

Intervention Type DRUG

Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Interventions

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Etrumadenant

Etrumadenant is an A2aR and A2bR antagonist.

Intervention Type DRUG

Zimberelimab

Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Intervention Type DRUG

Other Intervention Names

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AB928 AB122

Eligibility Criteria

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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:
7. 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:
8. 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.
9. 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.
10. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences, Inc.

Locations

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Scottsdale Healthcare Hospitals dba HonorHealth

Scottsdale, Arizona, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Site Status

Rocky Mountain Cancer Centers (Midtown)

Denver, Colorado, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

QUEST Research Institute

Royal Oak, Michigan, United States

Site Status

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Site Status

Prisma Health

Greenville, South Carolina, United States

Site Status

Texas Oncology, P.A. - Fort Worth Cancer Center

Fort Worth, Texas, United States

Site Status

Texas Oncology, P.A. - San Antonio Medical Center

San Antonio, Texas, United States

Site Status

Texas Oncology, P.A. - Tyler

Tyler, Texas, United States

Site Status

Medical Oncology Associates dba Summit Cancer Centers

Spokane, Washington, United States

Site Status

St. George Private Hospital

Kogarah, New South Wales, Australia

Site Status

Gallipoli Medical Research Foundation

Greenslopes, Queensland, Australia

Site Status

Cabrini Health Limited

Malvern, , Australia

Site Status

Countries

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United States Australia

Related Links

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https://trials.arcusbio.com/study/?id=ARC-5

ARC-5 - Lay Summary (English Version)

Other Identifiers

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ARC-5 (AB928CSP0005)

Identifier Type: -

Identifier Source: org_study_id

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