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.
In the dose escalation phase, the following will be assessed: * Arm A: escalating doses of etrumadenant in combination with PLD at standard doses will be assessed in participants with advanced metastatic triple-negative breast cancer or ovarian cancer. Eligible participants will receive oral administration of etrumadenant as well as intravenous (IV) infusion of PLD. The recommended dose (RDE) for expansion Arms 1 and 2 and escalation Arm C will be determined upon completion of this dose escalation arm. * Arm B: escalating doses of etrumadenant in combination with the NP at standard doses will also be assessed in participants with advanced metastatic TNBC. Eligible participants will receive oral administration of etrumadenant as well as NP infusion. The RDE of etrumadenant will be determined upon completion of this dose escalation arm. * Arm C: escalating doses of IPI-549 in combination with the RDE of etrumadenant (from Arm A) and PLD at standard doses will be assessed in participants with advanced metastatic TNBC or ovarian cancer. Eligible participants will receive oral administration of both etrumadenant and IPI-549 as well as IV infusion of PLD. The RDE of IPI-549 for expansion Arm 4 will be determined upon completion of this dose escalation arm. In the dose expansion phase, the following will be assessed: * Arms 1 and 2: Etrumadenant at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC or ovarian cancer. * Arm 3: Etrumadenant at the RDE in combination with NP at standard doses may be assessed in participants with advanced metastatic TNBC. * Arm 4: Etrumadenant and IPI-549 at the RDE in combination with PLD at standard doses may be assessed in participants with advanced metastatic TNBC. 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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Etrumadenant is an A2aR and A2bR antagonist for oral use
IPI-549 is a phosphoinositide-3-kinase-gamma inhibitor for oral use
Doxil is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous (IV) use
NP is a microtubule inhibitor for intravenous (IV) use
Scottsdale Healthcare Hospitals dba Honor Health Research Institute
Scottsdale, Arizona, United States
Arizona Clinical Research Center
Tucson, Arizona, United States
University of California, Los Angeles
Los Angeles, California, United States
Rocky Mountain Cancer Centers (Aurora)
Aurora, Colorado, United States
Miami Cancer Institute at Baptist Health
Miami, Florida, United States
Incidence of Adverse Events (AEs)
Time frame: From first dose date to 30 days after the last dose (Approximately 1 year)
Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
Time frame: From first dose date to 28 days after the first dose
Plasma concentration of etrumadenant
Time frame: Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Plasma concentration of IPI-549
Time frame: Recorded at baseline (prior to first dose), during the first 4 cycles of treatment (4 months) and at the end of treatment (i.e. in total approximately 5 months)
Percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), as determined by Investigator according to Response Evaluation in Solid Tumors (RECIST) v 1.1
Time frame: From study enrollment until participation discontinuation, first occurrence of progressive disease or death from any cause, whichever occurs first (approximately 3-5 years)
Percentage of participants with Disease Control (complete response, partial response, or stable disease) for > 6 months as determined by RECIST v1.1
Time frame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Duration of Response as determined by the Investigator according to RECIST v1.1
Time frame: From the date of the first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years)
Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1
Time frame: From start of the treatment up to first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
Overall Survival (OS) as determined by the Investigator according to RECIST v1.1
Time frame: From start of treatment up to death from any cause (up to approximately 3-5 years)
Percentage of etrumadenant target inhibition in peripheral blood
Time frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months)
Immunophenotyping activity in select immune subsets for etrumadenant and IPI-549 in peripheral blood
Time frame: Cycle 1 Day 1 through Cycle 4 Day 1 (4 months) and at the end of treatment (in total approximately 5 months).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Maryland Oncology Hematology, PA
Rockville, Maryland, United States
HealthPartners Institute Cancer Care Center
Saint Paul, Minnesota, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
Carolina BioOncology Institute
Huntersville, North Carolina, United States
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, United States
...and 17 more locations