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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Renal Cell Carcinoma; Breast Cancer; Colorectal Cancer; Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck; Bladder Cancer; Endometrial Cancer; Non-small Cell Lung Cancer; Castration-resistant Prostate Cancer; Merkel Cell Carcinoma; GastroEsophageal Cancer
• Intervention / Treatment: Drug: Etrumadenant; Drug: Zimberelimab

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Malvern, Australia, 3144
    • Cabrini Health Limited
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St. George Private Hospital
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Gallipoli Medical Research Foundation
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Hospitals DBA HonorHealth
  • California
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers (Midtown)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Royal Oak, Michigan, United States, 48073
      • Quest Research Institute
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A. - Fort Worth Cancer Center
    • San Antonio, Texas, United States, 78240
      • Texas Oncology, P.A. - San Antonio Medical Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology, P.A. - Tyler
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates dba Summit Cancer Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Progression Free Survival (PFS)	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	From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)
Overall Survival (OS)	OS as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types	From study start of treatment up to death from any cause (approximately 1-3 years)
Duration of Response (DOR)	DOR as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types	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)
Percentage of Participants with Disease Control	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	From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)
Percentage of participants with Objective Response	Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types	From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Investigators: Study Director: Medical Director, Arcus Biosciences, Inc.

Publications and helpful links

Helpful Links

• ARC-5 - Lay Summary (English Version)

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Actual): August 18, 2021
• Study Completion (Actual): September 3, 2021

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 23, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Carcinoma, Squamous Cell; Polyomavirus Infections; Carcinoma, Neuroendocrine; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma, Renal Cell; Carcinoma; Endometrial Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Merkel Cell
• Other Study ID Numbers: ARC-5 (AB928CSP0005)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No