A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors

Condition(s) studied

Investigational drug(s) / intervention(s)

ZN-A-1041: ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD

ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b: 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 + T-Dxd 5.4 mg/kg iv. for Phase 1b: 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 + PHESGO / Herceptin plus Perjeta injection for Phase 1b: 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 + T-DM1 3.6 mg/kg iv. for Phase 1c: 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 + T-Dxd 5.4 mg/kg iv. for Phase 1c: 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 + PHESGO / Herceptin plus Perjeta injection for Phase 1c: ZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion

Study summary

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).

Eligibility

Primary outcome measure(s)

• The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a — 23 days
  Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
• 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 — 21 days
  Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
• RP2D — Through study completion, an average of 1 year
  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.

Trial sites (36)