Back to resultsA Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies
Primary Purpose
TNBC - Triple-Negative Breast Cancer, Ovarian Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Etrumadenant
IPI-549
Pegylated liposomal doxorubicin (PLD)
nanoparticle albumin-bound paclitaxel (NP)
Sponsored by
About this trial
This is an interventional treatment trial for TNBC - Triple-Negative Breast Cancer focused on measuring Triple Negative Breast Cancer, TNBC, Ovarian Cancer
Eligibility Criteria
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)
Sites / Locations
- Scottsdale Healthcare Hospitals dba Honor Health Research Institute
- Arizona Clinical Research Center
- University of California, Los Angeles
- Rocky Mountain Cancer Centers (Aurora)
- Miami Cancer Institute at Baptist Health
- Maryland Oncology Hematology, PA
- HealthPartners Institute Cancer Care Center
- Comprehensive Cancer Centers of Nevada
- Carolina BioOncology Institute
- Willamette Valley Cancer Institute and Research Center
- Texas Oncology, P.A. - Austin (Midtown)
- Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center
- Texas Oncology, P.A. - Fort Worth Cancer Center
- Texas Oncology, P.A. - San Antonio Northeast
- Texas Oncology, P.A. - San Antonio Medical Center
- Texas Oncology, P.A. - Tyler
- Virginia Cancer Specialists, PC
- Virginia Oncology Associates
- Medical Oncology Associates dba Summit Cancer Centers
- MultiCare Regional Cancer Center
- Chris O'Brien Lifehouse
- The Kinghorn Cancer Centre
- St. George Private Hospital
- Macquarie University
- Pindara Private Hospital
- Peninsula & South Eastern Haematology and Oncology Group
- Cabrini Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose Escalation-Arm A
Dose Escalation-Arm B
Dose Escalation-Arm C
Dose Expansion-TNBC-Arm 1
Dose Expansion-Ovarian Cancer-Arm 2
Dose Expansion-TNBC-Arm 3
Dose Expansion-TNBC-Arm 4
Arm Description
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
The dose given will be determined from the dose escalation part (Arm A).
The dose given will be determined from the dose escalation part (Arm A).
The dose given will be determined from the dose escalation part (Arm B). .
The dose expansion will be determined from the dose escalation part (Arm C).
Outcomes
Primary Outcome Measures
Incidence of Adverse Events (AEs)
Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
Secondary Outcome Measures
Plasma concentration of etrumadenant
Plasma concentration of IPI-549
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
Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1
Duration of Response as determined by the Investigator according to RECIST v1.1
Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1
Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Percentage of etrumadenant target inhibition in peripheral blood
Immunophenotyping activity in select immune subsets for etrumadenant and IPI-549 in peripheral blood
Full Information
NCT ID
NCT03719326
First Posted
October 15, 2018
Last Updated
August 8, 2023
Sponsor
Arcus Biosciences, Inc.
Collaborators
Infinity Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03719326
Brief Title
A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies
Official Title
A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Breast or Gynecologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
October 15, 2018 (Actual)
Primary Completion Date
July 1, 2021 (Actual)
Study Completion Date
July 2, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arcus Biosciences, Inc.
Collaborators
Infinity Pharmaceuticals, 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 1/1b, 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TNBC - Triple-Negative Breast Cancer, Ovarian Cancer
Keywords
Triple Negative Breast Cancer, TNBC, Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 dose escalation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation-Arm A
Arm Type
Experimental
Arm Description
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Arm Title
Dose Escalation-Arm B
Arm Type
Experimental
Arm Description
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Arm Title
Dose Escalation-Arm C
Arm Type
Experimental
Arm Description
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Arm Title
Dose Expansion-TNBC-Arm 1
Arm Type
Experimental
Arm Description
The dose given will be determined from the dose escalation part (Arm A).
Arm Title
Dose Expansion-Ovarian Cancer-Arm 2
Arm Type
Experimental
Arm Description
The dose given will be determined from the dose escalation part (Arm A).
Arm Title
Dose Expansion-TNBC-Arm 3
Arm Type
Experimental
Arm Description
The dose given will be determined from the dose escalation part (Arm B). .
Arm Title
Dose Expansion-TNBC-Arm 4
Arm Type
Experimental
Arm Description
The dose expansion will be determined from the dose escalation part (Arm C).
Intervention Type
Drug
Intervention Name(s)
Etrumadenant
Other Intervention Name(s)
AB928
Intervention Description
Etrumadenant is an A2aR and A2bR antagonist for oral use
Intervention Type
Drug
Intervention Name(s)
IPI-549
Intervention Description
IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use
Intervention Type
Drug
Intervention Name(s)
Pegylated liposomal doxorubicin (PLD)
Intervention Description
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
Intervention Type
Drug
Intervention Name(s)
nanoparticle albumin-bound paclitaxel (NP)
Intervention Description
NP is a microtubule inhibitor for intravenous (IV) use
Primary Outcome Measure Information:
Title
Incidence of Adverse Events (AEs)
Time Frame
From first dose date to 30 days after the last dose (Approximately 1 year)
Title
Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
Time Frame
From first dose date to 28 days after the first dose
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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).
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
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 Honor Health Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Arizona Clinical Research Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Rocky Mountain Cancer Centers (Aurora)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Facility Name
Miami Cancer Institute at Baptist Health
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Maryland Oncology Hematology, PA
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
HealthPartners Institute Cancer Care Center
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Carolina BioOncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Texas Oncology, P.A. - Austin (Midtown)
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
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 Northeast
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
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
Virginia Cancer Specialists, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Medical Oncology Associates dba Summit Cancer Centers
City
Spokane
State/Province
Washington
ZIP/Postal Code
99216
Country
United States
Facility Name
MultiCare Regional Cancer Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Chris O'Brien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Kinghorn Cancer Centre
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
St. George Private Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Macquarie University
City
Macquarie
State/Province
New South Wales
ZIP/Postal Code
2109
Country
Australia
Facility Name
Pindara Private Hospital
City
Benowa
State/Province
Queensland
ZIP/Postal Code
4217
Country
Australia
Facility Name
Peninsula & South Eastern Haematology and Oncology Group
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
Cabrini Hospital
City
Malvern
State/Province
Victoria
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-2
Description
ARC-2 - Lay Summary (English Version)
Learn more about this trial
A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies
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