A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies

August 8, 2023 updated by: Arcus Biosciences, Inc.

A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Breast or Gynecologic Malignancies

This is a Phase 1/1b, 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 pegylated liposomal doxorubicin (PLD) with or without IPI-549 in participants with advanced metastatic triple-negative breast cancer (TNBC) or ovarian cancer, and etrumadenant in combination with nanoparticle albumin-bound-paclitaxel (NP) in participants with advanced metastatic TNBC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the dose escalation phase, the following will be assessed:

  • Arm A: escalating doses of etrumadenant in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer or ovarian cancer. Eligible participants will receive oral administration of etrumadenant as well as intravenous (IV) infusion of PLD. The recommended dose (RDE) for expansion Arms 1 and 2 and escalation Arm C will be determined upon completion of this dose escalation arm.
  • Arm B: escalating doses of etrumadenant in combination with the NP at standard doses will also be assessed in participants with advanced metastatic TNBC. Eligible participants will receive oral administration of etrumadenant as well as NP infusion. The RDE of etrumadenant will be determined upon completion of this dose escalation arm.
  • Arm C: escalating doses of IPI-549 in combination with the RDE of etrumadenant (from Arm A) and PLD at standard doses will be assessed in participants with advanced metastatic TNBC or ovarian cancer. Eligible participants will receive oral administration of both etrumadenant and IPI-549 as well as IV infusion of PLD. The RDE of IPI-549 for expansion Arm 4 will be determined upon completion of this dose escalation arm.

In the dose expansion phase, the following will be assessed:

  • Arms 1 and 2: Etrumadenant at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC or ovarian cancer.
  • Arm 3: Etrumadenant at the RDE in combination with NP at standard doses may be assessed in participants with advanced metastatic TNBC.
  • Arm 4: Etrumadenant and IPI-549 at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC.

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)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Darlinghurst, New South Wales, Australia, 2010
        • The Kinghorn Cancer Centre
      • Kogarah, New South Wales, Australia, 2217
        • St. George Private Hospital
      • Macquarie, New South Wales, Australia, 2109
        • Macquarie University
    • Queensland
      • Benowa, Queensland, Australia, 4217
        • Pindara Private Hospital
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Peninsula & South Eastern Haematology and Oncology Group
      • Malvern, Victoria, Australia, 3144
        • Cabrini Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Scottsdale Healthcare Hospitals dba Honor Health Research Institute
      • Tucson, Arizona, United States, 85715
        • Arizona Clinical Research Center
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Rocky Mountain Cancer Centers (Aurora)
    • Florida
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute at Baptist Health
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Maryland Oncology Hematology, Pa
    • Minnesota
      • Saint Paul, Minnesota, United States, 55101
        • HealthPartners Institute Cancer Care Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Carolina BioOncology Institute
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Willamette Valley Cancer Institute and Research Center
    • Texas
      • Austin, Texas, United States, 78705
        • Texas Oncology, P.A. - Austin (Midtown)
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology, P.A. - Fort Worth Cancer Center
      • San Antonio, Texas, United States, 78217
        • Texas Oncology, P.A. - San Antonio Northeast
      • San Antonio, Texas, United States, 78240
        • Texas Oncology, P.A. - San Antonio Medical Center
      • Tyler, Texas, United States, 75702
        • Texas Oncology, P.A. - Tyler
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates
    • Washington
      • Spokane, Washington, United States, 99216
        • Medical Oncology Associates dba Summit Cancer Centers
      • Tacoma, Washington, United States, 98405
        • MultiCare Regional Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female participants, 18 years or older
  • Measurable disease per radiographic evaluation
  • Performance status 0 or 1
  • Available archival tissue sample (within 2 years) or a fresh tumor biopsy may be required
  • Adequate organ, cardiac, and bone marrow function

  • Dose escalation

    • Participants with breast cancer:

      • Locally advanced or metastatic triple negative breast cancer (ER-negative, PgR-negative, and HER2-negative according to ASCO/CAP guidelines) with disease progression
      • No available alternative or curative therapy
      • Participants may have received any number of prior therapies for advanced/recurrent and progressive disease

    • Participants with ovarian cancer:

      • Locally advanced or metastatic ovarian cancer with disease progression
      • No available alternative or curative therapy
      • Participants may have received any number of prior therapies for advanced/recurrent and progressive disease

  • Dose expansion

    • Participants with breast cancer:

      • Locally advanced or metastatic triple negative breast cancer (ER-negative, PgR-negative, and HER2-negative according to ASCO/CAP guidelines)
      • Disease progression after no more than 3 prior lines of therapy

    • Participants with ovarian cancer:

      • Locally advanced or metastatic ovarian cancer that is platinum-resistant
      • Disease progression after no more than 3 prior lines of therapy

Exclusion Criteria:

  • Received a live, attenuated vaccine within 4 weeks prior to first study treatment
  • Prior anticancer treatment including approved agents, systemic radiotherapy, or investigational therapy within 4 weeks prior first study treatment
  • Cancer other than the disease under study within 2 years prior to study entry, except for some cancers with a low risk of spreading like non-melanoma skin cancers
  • Inability to swallow oral medications
  • Participant is breastfeeding, pregnant, or expects to become pregnant during the study
  • Active autoimmune disease or documented history of autoimmune disease within 2 years prior to first study treatment
  • History of peptic ulcer or stomach bleeding within 6 months prior to first study treatment
  • Use of drugs contraindicated by the protocol within 4 weeks prior to and during study treatment
  • Prior treatment with drugs that suppress the immune system within 2 weeks prior to first study treatment
  • Presence of metastases in the brain or cancer spreading into the cerebrospinal fluid - CSF (leptomeningeal disease)
  • HIV, Hepatitis B, and C test results negative prior to first study treatment
  • Major surgery within 4 weeks prior to first study treatment
  • Participants who have previously received maximum cumulative lifetime anthracycline dosage or baseline ejection fraction <50% (on heart echography)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation-Arm A
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Escalation-Arm B
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor for intravenous (IV) use
Experimental: Dose Escalation-Arm C
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Drug: IPI-549
IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use
Experimental: Dose Expansion-TNBC-Arm 1
The dose given will be determined from the dose escalation part (Arm A).
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Expansion-Ovarian Cancer-Arm 2
The dose given will be determined from the dose escalation part (Arm A).
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Experimental: Dose Expansion-TNBC-Arm 3
The dose given will be determined from the dose escalation part (Arm B). .
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor for intravenous (IV) use
Experimental: Dose Expansion-TNBC-Arm 4
The dose expansion will be determined from the dose escalation part (Arm C).
Drug: Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist for oral use
Other Names:
  • AB928
Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Drug: IPI-549
IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Adverse Events (AEs)
Time Frame: From first dose date to 30 days after the last dose (Approximately 1 year)
From first dose date to 30 days after the last dose (Approximately 1 year)
Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
Time Frame: From first dose date to 28 days after the first dose
From first dose date to 28 days after the first dose

Secondary Outcome Measures

Outcome Measure
Time Frame
Plasma concentration of etrumadenant
Time Frame: Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Plasma concentration of IPI-549
Time Frame: Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), as determined by Investigator according to Response Evaluation in Solid Tumors (RECIST) v 1.1
Time Frame: From study enrollment until participation discontinuation, first occurrence of progressive disease or death from any cause, whichever occurs first (approximately 3-5 years)
From study enrollment until participation discontinuation, first occurrence of progressive disease or death from any cause, whichever occurs first (approximately 3-5 years)
Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1
Time Frame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Duration of Response as determined by the Investigator according to RECIST v1.1
Time Frame: From the date of the first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
From the date of the first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1
Time Frame: From start of the treatment up to first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
From start of the treatment up to first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Time Frame: From start of treatment up to death from any cause (up to approximately 3-5 years)
From start of treatment up to death from any cause (up to approximately 3-5 years)
Percentage of etrumadenant target inhibition in peripheral blood
Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months)
Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months)
Immunophenotyping activity in select immune subsets for etrumadenant and IPI-549 in peripheral blood
Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months).
Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arcus Biosciences, Inc.

Collaborators

Infinity Pharmaceuticals, Inc.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 15, 2018

Primary Completion (Actual)

July 1, 2021

Study Completion (Actual)

July 2, 2021

Study Registration Dates

First Submitted

October 15, 2018

First Submitted That Met QC Criteria

October 23, 2018

First Posted (Actual)

October 25, 2018

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 8, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARC-2 (AB928CSP0002)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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