NCT03719326

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Oct 2018

Typical duration for phase_1

Geographic Reach
2 countries

27 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 15, 2018

Completed
Same day until next milestone

Study Start

First participant enrolled

October 15, 2018

Completed
10 days until next milestone

First Posted

Study publicly available on registry

October 25, 2018

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2021

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 2, 2021

Completed
Last Updated

May 24, 2024

Status Verified

May 1, 2024

Enrollment Period

2.7 years

First QC Date

October 15, 2018

Last Update Submit

May 23, 2024

Conditions

Keywords

Triple Negative Breast CancerTNBCOvarian Cancer

Outcome Measures

Primary Outcomes (2)

  • Incidence of Adverse Events (AEs)

    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

    From first dose date to 28 days after the first dose

Secondary Outcomes (9)

  • Plasma concentration of etrumadenant

    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

    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

    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

    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

    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)

  • +4 more secondary outcomes

Study Arms (7)

Dose Escalation-Arm A

EXPERIMENTAL

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.

Drug: EtrumadenantDrug: Pegylated liposomal doxorubicin (PLD)

Dose Escalation-Arm B

EXPERIMENTAL

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.

Drug: EtrumadenantDrug: nanoparticle albumin-bound paclitaxel (NP)

Dose Escalation-Arm C

EXPERIMENTAL

Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.

Drug: EtrumadenantDrug: IPI-549Drug: Pegylated liposomal doxorubicin (PLD)

Dose Expansion-TNBC-Arm 1

EXPERIMENTAL

The dose given will be determined from the dose escalation part (Arm A).

Drug: EtrumadenantDrug: Pegylated liposomal doxorubicin (PLD)

Dose Expansion-Ovarian Cancer-Arm 2

EXPERIMENTAL

The dose given will be determined from the dose escalation part (Arm A).

Drug: EtrumadenantDrug: Pegylated liposomal doxorubicin (PLD)

Dose Expansion-TNBC-Arm 3

EXPERIMENTAL

The dose given will be determined from the dose escalation part (Arm B). .

Drug: EtrumadenantDrug: nanoparticle albumin-bound paclitaxel (NP)

Dose Expansion-TNBC-Arm 4

EXPERIMENTAL

The dose expansion will be determined from the dose escalation part (Arm C).

Drug: EtrumadenantDrug: IPI-549Drug: Pegylated liposomal doxorubicin (PLD)

Interventions

Etrumadenant is an A2aR and A2bR antagonist for oral use

Also known as: AB928
Dose Escalation-Arm ADose Escalation-Arm BDose Escalation-Arm CDose Expansion-Ovarian Cancer-Arm 2Dose Expansion-TNBC-Arm 1Dose Expansion-TNBC-Arm 3Dose Expansion-TNBC-Arm 4

IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use

Dose Escalation-Arm CDose Expansion-TNBC-Arm 4

Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use

Dose Escalation-Arm ADose Escalation-Arm CDose Expansion-Ovarian Cancer-Arm 2Dose Expansion-TNBC-Arm 1Dose Expansion-TNBC-Arm 4

NP is a microtubule inhibitor for intravenous (IV) use

Dose Escalation-Arm BDose Expansion-TNBC-Arm 3

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +6 more criteria

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (27)

Scottsdale Healthcare Hospitals dba Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

Arizona Clinical Research Center

Tucson, Arizona, 85715, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Rocky Mountain Cancer Centers (Aurora)

Aurora, Colorado, 80012, United States

Location

Miami Cancer Institute at Baptist Health

Miami, Florida, 33176, United States

Location

Maryland Oncology Hematology, PA

Rockville, Maryland, 20850, United States

Location

HealthPartners Institute Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Texas Oncology, P.A. - Austin (Midtown)

Austin, Texas, 78705, United States

Location

Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

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

Fort Worth, Texas, 76104, United States

Location

Texas Oncology, P.A. - San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

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

San Antonio, Texas, 78240, United States

Location

Texas Oncology, P.A. - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Medical Oncology Associates dba Summit Cancer Centers

Spokane, Washington, 99216, United States

Location

MultiCare Regional Cancer Center

Tacoma, Washington, 98405, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Kinghorn Cancer Centre

Darlinghurst, New South Wales, 2010, Australia

Location

St. George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Macquarie University

Macquarie, New South Wales, 2109, Australia

Location

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Related Links

MeSH Terms

Conditions

Triple Negative Breast NeoplasmsOvarian Neoplasms

Interventions

IPI-549liposomal doxorubicinTaxes

Condition Hierarchy (Ancestors)

Breast NeoplasmsNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

EconomicsHealth Care Economics and Organizations

Study Officials

  • Medical Director

    Arcus Biosciences, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 3+3 dose escalation
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 15, 2018

First Posted

October 25, 2018

Study Start

October 15, 2018

Primary Completion

July 1, 2021

Study Completion

July 2, 2021

Last Updated

May 24, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, CSR
More information

Locations