Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer and 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 : August 1, 2019
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, pharmacodynamic, and clinical activity of AB928 in combination with pegylated liposomal doxorubicin (PLD) with or without IPI-549, or AB928 in combination with nanoparticle albumin-bound-paclitaxel (NP) in participants with advanced metastatic triple-negative breast cancer or ovarian cancer.

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:

Dose escalation of the following will be assessed:

  • escalating doses of AB928 in combination with pegylated liposomal doxorubicin (PLD) at standard doses in participants with advanced metastatic triple-negative breast cancer or ovarian cancer;
  • escalating doses of IPI-549 in combination with the recommended phase 2 dose (RP2D) of AB928 and PLD in participants with advanced metastatic triple-negative breast cancer or ovarian cancer;
  • escalating doses of AB928 in combination with the nanoparticle albumin-bound-paclitaxel (NP) will also be assessed in participants with advanced metastatic triple-negative breast cancer.

Dose expansion of the following will be assessed:

  • AB928 in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer or ovarian cancer. The dose of AB928 used will be determined based on the findings from the dose-escalation phase.
  • AB928 and IPI-549 in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer. The dose of AB928 and IPI-549 used will be determined based on the findings from the dose-escalation phase.
  • AB928 in combination with NP at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer. The dose of AB928 and NP used will be determined based on the findings from the dose-escalation phase.

AB928 and IPI-549 are administered orally, and PLD and NP are both administered via iv infusion.

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.


Layout table for study information
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 and 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 (PLD)
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB928 in combination with the standard PLD chemotherapy regimen in participants with triple-negative breast cancer or ovarian cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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

Experimental: Dose Escalation-Arm B (NP)
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of AB928 in combination with the standard NP chemotherapy regimen in participants with triple-negative breast cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

Drug: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor

Experimental: Dose Escalation-Arm C (Triplet)
Dose escalation is a 3+3 design, including a Dose Limiting Toxicity (DLT) evaluation period. The dose expansion dose level will be determined in this part with escalating doses of IPI-549 in combination with the AB928 dose determined from Arm A plus standard PLD chemotherapy regimen in participants with triple-negative breast cancer and ovarian cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

Drug: IPI-549
IPI-549 is a phosphoinositide-3kinase-gamma inhibitor

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

Experimental: Dose Expansion-TNBC-Arm 1 (PLD)
The dose given in dose expansion will be determined from the dose escalation part (Arm A). AB928 will be given in combination with the standard PLD chemotherapy regimen in participants with triple-negative breast cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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

Experimental: Dose Expansion-Ovarian-Arm 2 (PLD)
The dose given in dose expansion will be determined from the dose escalation part (Arm A). AB928 will be given in combination with the standard PLD chemotherapy regimen in participants with ovarian cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

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

Experimental: Dose Expansion-TNBC-Arm 3 (NP)
The dose given in dose expansion will be determined from the dose escalation part (Arm B). AB928 will be given in combination with the standard NP chemotherapy regimen in participants with triple-negative breast cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

Drug: nanoparticle albumin-bound paclitaxel (NP)
NP is a microtubule inhibitor

Experimental: Dose Expansion-TNBC-Arm 4 (Triplet)
The dose given in dose expansion will be determined from the dose escalation part (Arm C). IPI-549 will be given in combination with AB928 and standard PLD chemotherapy regimen in participants with triple-negative breast cancer.
Drug: AB928
AB928 is an A2aR and A2bR antagonist

Drug: IPI-549
IPI-549 is a phosphoinositide-3kinase-gamma inhibitor

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




Primary Outcome Measures :
  1. 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 therapy with Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. IPI-549 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

  9. IPI-549 pharmacokinetic (PK) Concentration: Tmax [ 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 time to maximum concentration using non-compartmental methods from serum plasma collection and analysis



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  1. Female participants ≥ 18 years of age at the time of screening;
  2. Must have at least 1 measurable lesion per RECIST v1.1;
  3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
  4. Confirm that an archival tissue sample is available and ≤ 6 months old; if not, a new biopsy of a tumor lesion must be obtained, or fresh biopsy at screening;
  5. Adequate organ and marrow function;
  6. Breast Cancer: Participants must have histologically confirmed ER-negative, PgR-negative, and HER2-negative breast cancer (per ASCO/CAP guidelines) that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists; OR Ovarian Cancer:Participants must have histologically confirmed ovarian cancer (per ASCO/CAP guidelines) that is metastatic, advanced or recurrent with progression for which no alternative or curative therapy exists;

Exclusion:

  1. Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational product.
  2. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational product hazardous
  3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  4. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 30 days after the last dose of investigational product administration.
  5. QTcF >480 ms with the exception for participants with riht or left bundle branch block.
  6. Prior surgery or GI dysfunction that may affect drug absorption for participants assigned to the IPI-549 arm(s).
  7. History of peptic ulcer and/or GI bleed within the past 6 months prior to screening for participants assigned to the IPI-549 arm(s).
  8. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in past 2 years
  9. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or prostate cancer.
  10. Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks prior to Day 1 or has not recovered (ie, ≥ Grade 1 or baseline) from AEs due to a previously administered agent
  11. Participants who are eligible for potentially curative available therapies or interventions.
  12. Use of other investigational drugs within 28 days of investigational product administration
  13. For participants who will be dosed with IPI-549, administration of any of the following within 1 week prior to the administration of investigational product:

    1. Strong inhibitors or inducers of cytochrome P450 (CYP)3A4, including grapefruit, grapefruit juice, and herbal supplements
    2. P-glycoprotein (P-gp) inhibitors and inducers
    3. Warfarin, phenytoin, or other substrates of CYP2C8 or CYP2C9 with a narrow therapeutic range
    4. Medications associated with QTc interval prolongation or Torsades de Pointes

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
Layout table for location contacts
Contact: Medical Director 510-694-6200 ClinicalTrialInquiry@arcusbio.com

  Show 29 Study Locations
Sponsors and Collaborators
Arcus Biosciences, Inc.
Infinity Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Arcus Biosciences, Inc.

Layout table for additonal information
Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03719326     History of Changes
Other Study ID Numbers: AB928CSP0002
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: August 1, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
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