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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03719326
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : July 8, 2020
Sponsor:
Collaborator:
Infinity Pharmaceuticals, Inc.
Information provided by (Responsible Party):
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 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 AB928 in combination with nanoparticle albumin-bound-paclitaxel (NP) in participants with advanced metastatic TNBC.

Condition or disease Intervention/treatment Phase
TNBC - Triple-Negative Breast Cancer Ovarian Cancer Drug: AB928 Drug: IPI-549 Drug: Pegylated liposomal doxorubicin (PLD) Drug: nanoparticle albumin-bound paclitaxel (NP) Phase 1

Detailed Description:

In the dose escalation phase, the following will be assessed:

  • Arm A: escalating doses of AB928 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 AB928 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 AB928 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 AB928 as well as NP infusion. The RDE of AB928 will be determined upon completion of this dose escalation arm.
  • Arm C: escalating doses of IPI-549 in combination with the RDE of AB928 (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 AB928 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: AB928 at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC or ovarian cancer.
  • Arm 3: AB928 at the RDE in combination with NP at standard doses may be assessed in participants with advanced metastatic TNBC.
  • Arm 4: AB928 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Breast or Gynecologic Malignancies
Actual Study Start Date : October 15, 2018
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : July 30, 2022


Arm Intervention/treatment
Experimental: Dose Escalation-Arm A
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use

Experimental: Dose Escalation-Arm B
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

Drug: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor for intravenous (IV) use

Experimental: Dose Escalation-Arm C
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period.
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

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

Experimental: Dose Expansion-TNBC-Arm 1
The dose given will be determined from the dose escalation part (Arm A).
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use

Experimental: Dose Expansion-Ovarian Cancer-Arm 2
The dose given will be determined from the dose escalation part (Arm A).
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

Drug: Pegylated liposomal doxorubicin (PLD)
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use

Experimental: Dose Expansion-TNBC-Arm 3
The dose given will be determined from the dose escalation part (Arm B). .
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

Drug: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor for intravenous (IV) use

Experimental: Dose Expansion-TNBC-Arm 4
The dose expansion will be determined from the dose escalation part (Arm C).
Drug: AB928
AB928 is an A2aR and A2bR antagonist for oral use

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




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: From first dose date to 30 days after the last dose (Approximately 1 year) ]
  2. 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 Measures :
  1. Plasma concentration of AB928 [ 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. Percentage of AB928 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) ]
  9. Immunophenotyping activity in select immune subsets for AB928 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). ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  1. Female participants, 18 years or older
  2. Measurable disease per radiographic evaluation
  3. Performance status 0 or 1
  4. Available archival tissue sample (within 2 years) or a fresh tumor biopsy may be required
  5. Adequate organ, cardiac, and bone marrow function
  6. Dose escalation

    1. 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
    2. 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
  7. Dose expansion

    1. 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
    2. 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:

  1. Received a live, attenuated vaccine within 4 weeks prior to first study treatment
  2. Prior anticancer treatment including approved agents, systemic radiotherapy, or investigational therapy within 4 weeks prior first study treatment
  3. 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
  4. Inability to swallow oral medications
  5. Participant is breastfeeding, pregnant, or expects to become pregnant during the study
  6. Active autoimmune disease or documented history of autoimmune disease within 2 years prior to first study treatment
  7. History of peptic ulcer or stomach bleeding within 6 months prior to first study treatment
  8. Use of drugs contraindicated by the protocol within 4 weeks prior to and during study treatment
  9. Prior treatment with drugs that suppress the immune system within 2 weeks prior to first study treatment
  10. Presence of metastases in the brain or cancer spreading into the cerebrospinal fluid - CSF (leptomeningeal disease)
  11. HIV, Hepatitis B, and C test results negative prior to first study treatment
  12. Major surgery within 4 weeks prior to first study treatment
  13. Participants who have previously received maximum cumulative lifetime anthracycline dosage or baseline ejection fraction <50% (on heart echography)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03719326


Contacts
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Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

Locations
Show Show 27 study locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Infinity Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Arcus Biosciences, Inc.
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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03719326    
Other Study ID Numbers: AB928CSP0002
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arcus Biosciences, Inc.:
Triple Negative Breast Cancer
TNBC
Ovarian Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Ovarian Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Doxorubicin
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors