Available in Brazil
This study will evaluate the efficacy and safety of zipalertinib in combination with
standard chemotherapy with pemetrexed and a platinum agent (either carboplatin or
cisplatin) in patients with previously untreated, locally advanced or metastatic
nonsquamous NSCLC harboring EGFR ex20ins mutations.
The study will be conducted in two parts:
- Part A: Safety lead-in to determine the recommended dose of zipalertinib in
combination with standard chemotherapy pemetrexed and a platinum agent (either
carboplatin or cisplatin) to be studied in Part B of the study.
- Part B: Randomized, controlled, open-label, multinational Phase 3 study to assess
the efficacy and safety of zipalertinib in combination with standard chemotherapy
with pemetrexed and a platinum agent (either carboplatin or cisplatin) compared to
standard chemotherapy alone. Patients randomized to the chemotherapy-only treatment
arm in Part B may receive treatment with zipalertinib as monotherapy after
BICR-assessed progressive disease (PD) is documented (optional "crossover arm").
An independent data monitoring committee (IDMC) will be established to monitor interim
safety Data.
A treatment cycle is defined as 21 days for both parts of the study.
Part A: Safety Lead-In The primary objective of Part A is to determine the recommended
dose of zipalertinib administered in combination with pemetrexed and a platinum agent
(either carboplatin or cisplatin) to be studied in the Phase 3 portion of this study.
Approximately 6-12 patients will receive zipalertinib administered at an initial dose of
zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or
cisplatin on a 21-day cycle. Patients may continue to receive study treatment until
documentation of progressive disease (PD) or until other withdrawal criteria are met,
whichever comes first. Patients will be enrolled using a rolling-6 design,35 and the
determination of the dose of zipalertinib to be used in Part B of the study will be
informed by the incidence of dose-limiting toxicities (DLTs) observed during Cycle 1.
Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following
completion of Part A.
Approximately 260 patients will be randomized on a 1:1 basis to receive pemetrexed and a
platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day
cycle.
Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to
receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until
documentation of PD or until other withdrawal criteria are met, whichever comes first.
272Patients around the world