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.
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
Drug | Synonyms | Arms |
---|
AB928 | | Dose Escalation-Arm A (PLD) |
IPI-549 | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Escalation-Arm A (PLD) | Experimental | 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. | - AB928
- Pegylated liposomal doxorubicin (PLD)
|
Dose Escalation-Arm B (NP) | Experimental | 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. | - AB928
- nanoparticle albumin-bound paclitaxel (NP)
|
Dose Escalation-Arm C (Triplet) | Experimental | 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. | - AB928
- IPI-549
- Pegylated liposomal doxorubicin (PLD)
|
Dose Expansion-TNBC-Arm 1 (PLD) | Experimental | 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. | - AB928
- Pegylated liposomal doxorubicin (PLD)
|
Dose Expansion-Ovarian-Arm 2 (PLD) | Experimental | 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. | - AB928
- Pegylated liposomal doxorubicin (PLD)
|
Dose Expansion-TNBC-Arm 3 (NP) | Experimental | 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. | - AB928
- nanoparticle albumin-bound paclitaxel (NP)
|
Dose Expansion-TNBC-Arm 4 (Triplet) | Experimental | 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. | - 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