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Trial record 1 of 1 for:    NCT03719326
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A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer and Gynecologic Malignancies

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ClinicalTrials.gov Identifier: NCT03719326
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : November 6, 2018
Sponsor:
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) 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: Pegylated liposomal doxorubicin Phase 1

Detailed Description:

Dose escalation of AB928 in combination with pegylated liposomal doxorubicin (PLD) at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer or ovarian cancer. In this dose escalation combination study participants will receive oral administration of AB928 as well as iv infusion of PLD.

Dose expansion of 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.

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  (Clinical Trial)
Estimated Enrollment : 98 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 : July 30, 2020
Estimated Study Completion Date : July 30, 2021


Arm Intervention/treatment
Experimental: Dose Escalation
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
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous use

Experimental: Dose Expansion-TNBC
The dose given in dose expansion will be determined from the dose escalation part. 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
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous use

Experimental: Dose Expansion-Ovarian
The dose given in dose expansion will be determined from the dose escalation part. 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
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 with PLD 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. 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

  5. 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

  6. 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

  7. 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



Information from the National Library of Medicine

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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

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 AB928 in combination with PLD.
  5. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in past 2 years
  6. 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.
  7. 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
  8. Participants who are eligible for potentially curative available therapies or interventions.
  9. Use of other investigational drugs within 28 days of investigational product administration

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

Locations
United States, North Carolina
Huntersville, NC Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Australia, New South Wales
Sydney, Australia Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Principal Investigator         
Principal Investigator: Principal Investigator         
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
Study Director: Medical Director Arcus Biosciences, Inc.

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: November 6, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action