This will be a Phase 1, multicenter, open-label trial to evaluate the safety, tolerability, PK and efficacy of ZN-A-1041 as a monotherapy or in combination in participants with HER2-positive advanced solid tumors with or without brain metastases. The study will consist of three phases: Phase 1a (dose escalation with ZN-A-1041 monotherapy), Phase 1b (dose escalation with ZN-A-1041 combination therapy) and Phase 1c (dose expansion with ZN-A-1041 combination therapy).
This study is composed of three parts designed to evaluate the safety and efficacy of ZN-A-1041 in participants with HER2-positive advanced solid tumors. Phase 1a (Monotherapy Dose Escalation): In this first phase, participants will receive ZN-A-1041 alone. The study will begin with a low dose of ZN-A-1041, which will be gradually increased in new groups of participants to find the highest dose that can be given safely. This will establish the recommended dose for further study. Phase 1b (Combination Dose Escalation): In the second phase, the study will evaluate the safety of giving ZN-A-1041 together with established standard-of-care therapies for HER2-positive breast cancer. Participants will be enrolled into one of three combination arms to receive ZN-A-1041 with either T-DM1, T-DXd, or a pertuzumab/trastuzumab-based regimen. This phase will identify the recommended dose for these combination therapies. Phase 1c (Combination Dose Expansion): In the final phase, additional participants will be enrolled to receive ZN-A-1041 at the recommended combination doses identified in Phase 1b. This will allow for a more thorough evaluation of the safety and preliminary efficacy of these treatment regimens. Throughout the study, participants will undergo screening, treatment, and follow-up periods to collect comprehensive data on the safety, tolerability, pharmacokinetics, and anti-tumor activity of ZN-A-1041, both as a single agent and in combination.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
210
ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD
ZN-A-1041: BID via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041: BID via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041: BID via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion
ZN-A-1041: BID via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041: BID via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion
Arizona Clinical Research Center, Inc.;Hematology Oncology Physicians - Aoa
Tucson, Arizona, United States
TOI Clinical Research
Cerritos, California, United States
UCSF Helen Diller Family CCC
San Francisco, California, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Hospital
Ann Arbor, Michigan, United States
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
Time frame: 23 days
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 in Combination with T-DM1 or with T-DXd, or in Combination with PHESGO or Herceptin plus Perjeta
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
Time frame: 21 days
RP2D
To evaluate the safety of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta in participants on the RP2D.
Time frame: Through study completion, an average of 1 year
Plasma, Urine and Potentially Cerebrospinal Fluid (CSF) Level of ZN-A-1041 and its Main Metabolites
To assess the PK of ZN-A-1041 and its major metabolites.
Time frame: From baseline to cycle 9 (each cycel is 21 days)
Serum Level of Combination Drugs in Phase 1c
To assess the serum concentration of combination drugs.
Time frame: Through study completion, an average of 2 year
Anti-drug Antibodies (ADAs) Evaluation in Phase 1c
To assess the incidence of ADAs.
Time frame: Through study completion, an average of 2 year
Overall Response Rate (ORR)
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
Time frame: Through study completion, an average of 2 year
Progression Free Survival (PFS)
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
Time frame: Through study completion, an average of 2 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Duke University School of Medicine
Durham, North Carolina, United States
MD Anderson Cancer Center
Houston, Texas, United States
Geelong Hospital
Geelong, Victoria, Australia
Sunshine Hospital
St Albans, Victoria, Australia
...and 26 more locations