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

Primary Purpose

Non-small Cell Lung Cancer, Squamous Cell Carcinoma of the Head and Neck, Breast Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Etrumadenant
Zimberelimab
Sponsored by
Arcus Biosciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Scottsdale Healthcare Hospitals dba HonorHealth
  • University of California, Los Angeles
  • The Angeles Clinic and Research Institute
  • Rocky Mountain Cancer Centers (Midtown)
  • University of Michigan
  • QUEST Research Institute
  • Carolina BioOncology Institute
  • Prisma Health
  • Texas Oncology, P.A. - Fort Worth Cancer Center
  • Texas Oncology, P.A. - San Antonio Medical Center
  • Texas Oncology, P.A. - Tyler
  • Medical Oncology Associates dba Summit Cancer Centers
  • St. George Private Hospital
  • Gallipoli Medical Research Foundation
  • Cabrini Health Limited

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Escalation

Dose Expansion-advanced clear-cell RCC

Dose Expansion-mCRPC

Arm Description

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.

Etrumadenant at RP2D + zimberelimab

Etrumadenant at RP2D + zimberelimab

Outcomes

Primary Outcome Measures

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.
Percentage of participants who experience a Dose Limiting Toxicity

Secondary Outcome Measures

Etrumadenant Peak Serum Concentration: Cmax
Zimberelimab Peak Serum Concentration: Cmax
Etrumadenant Time of Peak Concentration: Tmax
Zimberelimab Time of Peak Concentration: Tmax
Percentage of participants with anti-drug antibodies to zimberelimab
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
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
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
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
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

Full Information

First Posted
July 17, 2018
Last Updated
August 8, 2023
Sponsor
Arcus Biosciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03629756
Brief Title
A Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Official Title
A Phase 1 Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Advanced Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
July 24, 2018 (Actual)
Primary Completion Date
August 18, 2021 (Actual)
Study Completion Date
September 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arcus Biosciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 Dose escalation design.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Expansion-advanced clear-cell RCC
Arm Type
Experimental
Arm Description
Etrumadenant at RP2D + zimberelimab
Arm Title
Dose Expansion-mCRPC
Arm Type
Experimental
Arm Description
Etrumadenant at RP2D + zimberelimab
Intervention Type
Drug
Intervention Name(s)
Etrumadenant
Other Intervention Name(s)
AB928
Intervention Description
Etrumadenant is an A2aR and A2bR antagonist.
Intervention Type
Drug
Intervention Name(s)
Zimberelimab
Other Intervention Name(s)
AB122
Intervention Description
Zimberelimab is a fully human anti-PD-1 monoclonal antibody.
Primary Outcome Measure Information:
Title
Percentage of participants with Adverse Events
Description
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.
Time Frame
From first dose date to 90 days after the last dose (approximately 3 years)
Title
Percentage of participants who experience a Dose Limiting Toxicity
Time Frame
From first study treatment administration through Day 28
Secondary Outcome Measure Information:
Title
Etrumadenant Peak Serum Concentration: Cmax
Time Frame
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Title
Zimberelimab Peak Serum Concentration: Cmax
Time Frame
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Title
Etrumadenant Time of Peak Concentration: Tmax
Time Frame
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Title
Zimberelimab Time of Peak Concentration: Tmax
Time Frame
Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Title
Percentage of participants with anti-drug antibodies to zimberelimab
Time Frame
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)
Title
Progression Free Survival (PFS)
Description
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
Time Frame
From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)
Title
Overall Survival (OS)
Description
OS as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
Time Frame
From study start of treatment up to death from any cause (approximately 1-3 years)
Title
Duration of Response (DOR)
Description
DOR as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
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 (approximately 1-3 years)
Title
Percentage of Participants with Disease Control
Description
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
Time Frame
From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)
Title
Percentage of participants with Objective Response
Description
Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
Time Frame
From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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.). Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Arcus Biosciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Scottsdale Healthcare Hospitals dba HonorHealth
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
The Angeles Clinic and Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Rocky Mountain Cancer Centers (Midtown)
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
QUEST Research Institute
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Carolina BioOncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Prisma Health
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Texas Oncology, P.A. - Fort Worth Cancer Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Oncology, P.A. - San Antonio Medical Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Texas Oncology, P.A. - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Medical Oncology Associates dba Summit Cancer Centers
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
Facility Name
St. George Private Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Gallipoli Medical Research Foundation
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Facility Name
Cabrini Health Limited
City
Malvern
ZIP/Postal Code
3144
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://trials.arcusbio.com/our-transparency-policy
Links:
URL
https://trials.arcusbio.com/study/?id=ARC-5
Description
ARC-5 - Lay Summary (English Version)

Learn more about this trial

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

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