Clinical Trials /

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

NCT03719326

Description:

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.

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-Arm A (PLD)
IPI-549Dose Escalation-Arm C (Triplet)
Pegylated liposomal doxorubicin (PLD)Dose Escalation-Arm A (PLD)
nanoparticle albumin-bound paclitaxel (NP)Dose Escalation-Arm B (NP)

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) 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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation-Arm A (PLD)ExperimentalDose 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 (PLD)
Dose Escalation-Arm B (NP)ExperimentalDose 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.
  • AB928
  • nanoparticle albumin-bound paclitaxel (NP)
Dose Escalation-Arm C (Triplet)ExperimentalDose 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.
  • AB928
  • IPI-549
  • Pegylated liposomal doxorubicin (PLD)
Dose Expansion-TNBC-Arm 1 (PLD)ExperimentalThe 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.
  • AB928
  • Pegylated liposomal doxorubicin (PLD)
Dose Expansion-Ovarian-Arm 2 (PLD)ExperimentalThe 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.
  • AB928
  • Pegylated liposomal doxorubicin (PLD)
Dose Expansion-TNBC-Arm 3 (NP)ExperimentalThe 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.
  • AB928
  • nanoparticle albumin-bound paclitaxel (NP)
Dose Expansion-TNBC-Arm 4 (Triplet)ExperimentalThe 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.
  • AB928
  • IPI-549
  • Pegylated liposomal doxorubicin (PLD)

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 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
      
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 therapy 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: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: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: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: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
Measure: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)
Safety Issue:
Description:Measured using the area under the concentration-time curve from serum plasma collection and analysis
Measure: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)
Safety Issue:
Description:Measured using the time to maximum concentration using non-compartmental methods from serum plasma collection and analysis

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arcus Biosciences, Inc.

Last Updated

December 20, 2019