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

NCT ID: NCT03719326

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-15

Study Completion Date

2021-07-02

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

TNBC - Triple-Negative Breast Cancer Ovarian Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

3+3 dose escalation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dose Escalation-Arm A

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

Pegylated liposomal doxorubicin (PLD)

Intervention Type DRUG

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

Dose Escalation-Arm B

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

nanoparticle albumin-bound paclitaxel (NP)

Intervention Type DRUG

NP is a microtubule inhibitor for intravenous (IV) use

Dose Escalation-Arm C

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

IPI-549

Intervention Type DRUG

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

Pegylated liposomal doxorubicin (PLD)

Intervention Type DRUG

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

Dose Expansion-TNBC-Arm 1

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

Pegylated liposomal doxorubicin (PLD)

Intervention Type DRUG

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

Dose Expansion-Ovarian Cancer-Arm 2

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

Pegylated liposomal doxorubicin (PLD)

Intervention Type DRUG

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

Dose Expansion-TNBC-Arm 3

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

nanoparticle albumin-bound paclitaxel (NP)

Intervention Type DRUG

NP is a microtubule inhibitor for intravenous (IV) use

Dose Expansion-TNBC-Arm 4

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

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is an A2aR and A2bR antagonist for oral use

IPI-549

Intervention Type DRUG

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

Pegylated liposomal doxorubicin (PLD)

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Etrumadenant

Etrumadenant is an A2aR and A2bR antagonist for oral use

Intervention Type DRUG

IPI-549

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

Intervention Type DRUG

Pegylated liposomal doxorubicin (PLD)

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

Intervention Type DRUG

nanoparticle albumin-bound paclitaxel (NP)

NP is a microtubule inhibitor for intravenous (IV) use

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

AB928

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Infinity Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences, Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Scottsdale Healthcare Hospitals dba Honor Health Research Institute

Scottsdale, Arizona, United States

Site Status

Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

Rocky Mountain Cancer Centers (Aurora)

Aurora, Colorado, United States

Site Status

Miami Cancer Institute at Baptist Health

Miami, Florida, United States

Site Status

Maryland Oncology Hematology, PA

Rockville, Maryland, United States

Site Status

HealthPartners Institute Cancer Care Center

Saint Paul, Minnesota, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Site Status

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, United States

Site Status

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

Austin, Texas, United States

Site Status

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

Dallas, Texas, 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 Northeast

San Antonio, 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

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Medical Oncology Associates dba Summit Cancer Centers

Spokane, Washington, United States

Site Status

MultiCare Regional Cancer Center

Tacoma, Washington, United States

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

The Kinghorn Cancer Centre

Darlinghurst, New South Wales, Australia

Site Status

St. George Private Hospital

Kogarah, New South Wales, Australia

Site Status

Macquarie University

Macquarie, New South Wales, Australia

Site Status

Pindara Private Hospital

Benowa, Queensland, Australia

Site Status

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Site Status

Cabrini Hospital

Malvern, Victoria, Australia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia

Related Links

Access external resources that provide additional context or updates about the study.

https://trials.arcusbio.com/study/?id=ARC-2

ARC-2 - Lay Summary (English Version)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ARC-2 (AB928CSP0002)

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.