A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer or Gynecologic Malignancies
- Conditions
- TNBC - Triple-Negative Breast CancerOvarian Cancer
- Interventions
- Registration Number
- NCT03719326
- Lead Sponsor
- Arcus Biosciences, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 35
-
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
-
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion-TNBC-Arm 3 Etrumadenant The dose given will be determined from the dose escalation part (Arm B). . Dose Expansion-TNBC-Arm 4 Pegylated liposomal doxorubicin (PLD) The dose expansion will be determined from the dose escalation part (Arm C). Dose Escalation-Arm B Etrumadenant Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Expansion-TNBC-Arm 3 nanoparticle albumin-bound paclitaxel (NP) The dose given will be determined from the dose escalation part (Arm B). . Dose Escalation-Arm C IPI-549 Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Escalation-Arm A Pegylated liposomal doxorubicin (PLD) Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Escalation-Arm B nanoparticle albumin-bound paclitaxel (NP) Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Expansion-Ovarian Cancer-Arm 2 Pegylated liposomal doxorubicin (PLD) The dose given will be determined from the dose escalation part (Arm A). Dose Escalation-Arm C Pegylated liposomal doxorubicin (PLD) Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Expansion-TNBC-Arm 1 Pegylated liposomal doxorubicin (PLD) The dose given will be determined from the dose escalation part (Arm A). Dose Expansion-Ovarian Cancer-Arm 2 Etrumadenant The dose given will be determined from the dose escalation part (Arm A). Dose Expansion-TNBC-Arm 4 IPI-549 The dose expansion will be determined from the dose escalation part (Arm C). Dose Escalation-Arm A Etrumadenant Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Escalation-Arm C Etrumadenant Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. Dose Expansion-TNBC-Arm 1 Etrumadenant The dose given will be determined from the dose escalation part (Arm A). Dose Expansion-TNBC-Arm 4 Etrumadenant The dose expansion will be determined from the dose escalation part (Arm C).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1 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) Percentage of etrumadenant target inhibition in peripheral blood 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 Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (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) 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) 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) Overall Survival (OS) as determined by the Investigator according to RECIST v1.1 From start of treatment up to death from any cause (up to 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)
Trial Locations
- Locations (27)
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Miami Cancer Institute at Baptist Health
🇺🇸Miami, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Texas Oncology, P.A. - San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Arizona Clinical Research Center
🇺🇸Tucson, Arizona, United States
Scottsdale Healthcare Hospitals dba Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
Maryland Oncology Hematology, PA
🇺🇸Rockville, Maryland, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
HealthPartners Institute Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Carolina BioOncology Institute
🇺🇸Huntersville, North Carolina, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Texas Oncology, P.A. - Austin (Midtown)
🇺🇸Austin, Texas, United States
Texas Oncology, P.A. - Tyler
🇺🇸Tyler, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Texas Oncology, P.A. - San Antonio Northeast
🇺🇸San Antonio, Texas, United States
Medical Oncology Associates dba Summit Cancer Centers
🇺🇸Spokane, Washington, United States
St. George Private Hospital
🇦🇺Kogarah, New South Wales, Australia
MultiCare Regional Cancer Center
🇺🇸Tacoma, Washington, United States
The Kinghorn Cancer Centre
🇦🇺Darlinghurst, New South Wales, Australia
Macquarie University
🇦🇺Macquarie, New South Wales, Australia
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
Cabrini Hospital
🇦🇺Malvern, Victoria, Australia
Rocky Mountain Cancer Centers (Aurora)
🇺🇸Aurora, Colorado, United States
Texas Oncology, P.A. - Fort Worth Cancer Center
🇺🇸Fort Worth, Texas, United States