EGFR-mutant NSCLC
Conditions
Interventions
-Cohort A: Zipalertinib will be administered orally at a dose of 100 mg twice daily.
-Cohort B: Zipalertinib (100mg) will be administered orally BID. Pemetrexed will be administered intravenously at
Sponsors
Hida Toyoaki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is >= 18 years of age at the time of informed consent. 2. Histologically or cytologically confirmed locally advanced or metastatic nonsqauamous NSCLC, characterized at or after the time of locally advanced or metastatic disease diagnosis by either EGFR Exon 19del or Exon 21 L858R mutation. 3. Documented MET overexpression or amplification after osimertinib failure (Cohort C Part2 only). 4. Tumor tissue available for submission collected after progression on osimertinib treatment, with minimum quantity sufficient to evaluate mutation status of biomarkers and, where possible, other biomarkers. Patients with insufficient tissue or unavailable may be eligible following discussion with the Sponsor. 5. At least one measurable lesion as determined per RECIST 1.1 (Part 2 only). 6. Patients with any of the following; a.No brain metastasis. b.Brain metastasis(es) who have previously received definitive local treatment and have stable central nervous system disease (defined as being neurologically stable and without requiring escalating corticosteroid and/or anti-convulsant medications for at least 14 days prior to enrollment) are eligible. Any definitive local treatment to brain metastases must have been completed at least 14 days prior to enrollment and the patient can be receiving no greater than 10 mg prednisone or equivalent daily at enrollment for the treatment of intracranial disease. c.Asymptomatic brain metastases <= 2 cm in size can be eligible for inclusion if, in the opinion of the investigator, immediate definitive treatment is not indicated.
Exclusion criteria
Exclusion criteria: 1. Documented C797S mutation-positive status after osimertinib failure (Cohorts A and B only). 2. Have any unresolved toxicity of Grade >= 2 from previous anticancer treatment except for Grade 2 alopecia or skin pigmentation. Patients with other chronic but stable Grade 2 toxicities may be allowed to enroll after agreement between the investigator and Sponsor. 3. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed (Cohort B only). 4. Corrected visual acuity < 0.5 (using the International Visual Acuity Measurement Standard) for both eyes (Cohort D only).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 - Incidence of dose-limiting toxicities (DLTs) according to the Common Terminology Criteria of Adverse Events Version 5.0 (CTCAE v.5.0) during Cycle 1 Part 2 - Investigator-assessed objective response rate (ORR) per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | — |
Contacts
Public ContactKana Matsubara
Taiho Pharmaceutical Co., Ltd.
Outcome results
None listed