Clinical trial NCT03719326: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: TNBC - Triple-Negative Breast Cancer
Ovarian Cancer
Keywords: Triple Negative Breast Cancer
TNBC
Ovarian Cancer
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Infinity Pharmaceuticals, Inc.
First posted: 2018-10-25
Enrollment: 35
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 dose escalation
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: From first dose date to 30 days after the last dose (Approximately 1 year)
measure: Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
timeFrame: From first dose date to 28 days after the first dose
Secondary outcomes:
measure: Plasma concentration of etrumadenant
timeFrame: 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)
measure: Plasma concentration of IPI-549
timeFrame: 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)
measure: 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
timeFrame: From study enrollment until participation discontinuation, first occurrence of progressive disease or death from any cause, whichever occurs first (approximately 3-5 years)
measure: Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1
timeFrame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
measure: Duration of Response as determined by the Investigator according to RECIST v1.1
timeFrame: 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)
measure: Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1
timeFrame: 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)
measure: Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
timeFrame: From start of treatment up to death from any cause (up to approximately 3-5 years)
measure: Percentage of etrumadenant target inhibition in peripheral blood
timeFrame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months)
measure: Immunophenotyping activity in select immune subsets for etrumadenant and IPI-549 in peripheral blood
timeFrame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months).
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals dba Honor Health Research Institute
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Aurora)
state: Colorado
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health
state: Florida
city: Rockville
country: United States
facility: Maryland Oncology Hematology, PA
state: Maryland
city: Saint Paul
country: United States
facility: HealthPartners Institute Cancer Care Center
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Austin
country: United States
facility: Texas Oncology, P.A. - Austin (Midtown)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology, P.A. - San Antonio Northeast
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology, P.A. - San Antonio Medical Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates dba Summit Cancer Centers
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Private Hospital
state: New South Wales
city: Macquarie
country: Australia
facility: Macquarie University
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: