Clinical Trials /

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

NCT03719326

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Safety/Tolerability of Immunotherapy Combinations in Participants With Triple-Negative Breast Cancer and Gynecologic Malignancies
  • Official Title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Breast and Gynecologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: AB928CSP0002
  • NCT ID: NCT03719326

Conditions

  • TNBC - Triple-Negative Breast Cancer
  • Ovarian Cancer

Interventions

DrugSynonymsArms
AB928Dose Escalation
Pegylated liposomal doxorubicinDose Escalation

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDose 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.
  • AB928
  • Pegylated liposomal doxorubicin
Dose Expansion-TNBCExperimentalThe 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.
  • AB928
  • Pegylated liposomal doxorubicin
Dose Expansion-OvarianExperimentalThe 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.
  • AB928
  • Pegylated liposomal doxorubicin

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description: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

Measure: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)
Safety Issue:
Description:Measured using the area under the concentration-time curve from serum plasma collection and analysis
Measure: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
Safety Issue:
Description:Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis
Measure:Clinical activity of combination therapy
Time Frame:Recorded at Baseline (Screening), every 8 weeks until progression (approximately 6 months, however can be longer).
Safety Issue:
Description:Tumor assessments over time will be measured using RECIST v1.0.
Measure: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.
Safety Issue:
Description:Receptor Occupancy May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
Measure: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.
Safety Issue:
Description:Immunophenotyping May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
Measure: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.
Safety Issue:
Description:Gene Expression May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples
Measure: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.
Safety Issue:
Description:Cytokines May be Summarized by Dose Group and Subject Over Time by Aggregating Data From Exploratory Biomarkers Collected From Peripheral Blood Samples

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Arcus Biosciences, Inc.

Last Updated