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

• ClinicalTrials.gov Identifier: NCT03719326
• Recruitment Status: Completed
• First Posted: October 25, 2018
• Last Update Posted: December 27, 2022
• Sponsor: Arcus Biosciences, Inc.
• Collaborator: Infinity Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Arcus Biosciences, Inc.

Tracking Information

• First Submitted Date: October 15, 2018
• First Posted Date: October 25, 2018
• Last Update Posted Date: December 27, 2022
• Actual Study Start Date: October 15, 2018
• Actual Primary Completion Date: July 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2020)

• Incidence of Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: From first dose date to 28 days after the first dose ]

Original Primary Outcome Measures (submitted: October 23, 2018)

Number of Participants with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 [ Time Frame: From first dose date to 90 days after the last dose (Approximately 1 year) ]

Number of Participants Treated with AB928 in Combination with PLD with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

Current Secondary Outcome Measures (submitted: September 25, 2020)

• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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). ]

Original Secondary Outcome Measures (submitted: October 23, 2018)

• AB928 pharmacokinetic (PK) Concentration: Cmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and every 30 days until 6 months post last dose (i.e. at 30, 60 and 90 days, and 6 months) ]
  Measured using the area under the concentration-time curve from serum plasma collection and analysis
• AB928 pharmacokinetic (PK) Concentration: Tmax [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), 30 and 90 days after treatment ]
  Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
• Clinical activity of combination therapy [ Time Frame: Recorded at Baseline (Screening), every 8 weeks until progression (approximately 6 months, however can be longer). ]
  Tumor assessments over time will be measured using RECIST v1.0.
• AB928 Receptor Occupancy [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
  Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
• AB928 Immunophenotyping [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
  Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
• AB928 Gene Expression [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
  Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
• AB928 Cytokines [ Time Frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and 30 days after treatment ends (in total approximately 6 months). Each Cycle is 28 days. ]
  Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

3+3 dose escalation

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• TNBC - Triple-Negative Breast Cancer
• Ovarian Cancer

Intervention

• Drug: Etrumadenant
  Etrumadenant is an A2aR and A2bR antagonist for oral use
  Other Name: AB928
• Drug: IPI-549
  IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use
• Drug: Pegylated liposomal doxorubicin (PLD)
  Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
• Drug: nanoparticle albumin-bound paclitaxel (NP)
  NP is a microtubule inhibitor for intravenous (IV) use

Study Arms

• Experimental: Dose Escalation-Arm A
  Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
  Interventions:

  • Drug: Etrumadenant
  • Drug: Pegylated liposomal doxorubicin (PLD)
• Experimental: Dose Escalation-Arm B
  Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
  Interventions:

  • Drug: Etrumadenant
  • Drug: nanoparticle albumin-bound paclitaxel (NP)
• Experimental: Dose Escalation-Arm C
  Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
  Interventions:

  • Drug: Etrumadenant
  • Drug: IPI-549
  • Drug: Pegylated liposomal doxorubicin (PLD)
• Experimental: Dose Expansion-TNBC-Arm 1
  The dose given will be determined from the dose escalation part (Arm A).
  Interventions:

  • Drug: Etrumadenant
  • Drug: Pegylated liposomal doxorubicin (PLD)
• Experimental: Dose Expansion-Ovarian Cancer-Arm 2
  The dose given will be determined from the dose escalation part (Arm A).
  Interventions:

  • Drug: Etrumadenant
  • Drug: Pegylated liposomal doxorubicin (PLD)
• Experimental: Dose Expansion-TNBC-Arm 3
  The dose given will be determined from the dose escalation part (Arm B). .
  Interventions:

  • Drug: Etrumadenant
  • Drug: nanoparticle albumin-bound paclitaxel (NP)
• Experimental: Dose Expansion-TNBC-Arm 4
  The dose expansion will be determined from the dose escalation part (Arm C).
  Interventions:

  • Drug: Etrumadenant
  • Drug: IPI-549
  • Drug: Pegylated liposomal doxorubicin (PLD)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 8, 2021): 35
• Original Estimated Enrollment (submitted: October 23, 2018): 98
• Actual Study Completion Date: July 2, 2021
• Actual Primary Completion Date: July 1, 2021 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States
• Removed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT03719326
• Other Study ID Numbers: ARC-2 (AB928CSP0002)
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.

• Current Responsible Party: Arcus Biosciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Arcus Biosciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Infinity Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director; Arcus Biosciences, Inc.

• PRS Account: Arcus Biosciences, Inc.
• Verification Date: December 2022