WSD0922-FU for the Treatment of Glioblastoma, Anaplastic Astrocytoma, or Non-small Cell Lung Cancer With Central Nervous System Metastases

Description

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of EGFR/EGFRvIII inhibitor WSD0922-FU (WSD0922-FU) in subjects with recurrent glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) and central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate the incidence of treatment-emergent adverse events (TEAEs) related to WSD0922-FU.

II. To assess anti-tumor activity: intracranial and extracranial overall response rate (ORR), and change in tumor size compared with baseline according to Response Assessment in Neuro-Oncology (RANO) criteria for GBM/AA and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for NSCLC.

III. To assess anti-tumor activity: intracranial and extracranial disease control rate (DCR) and change in tumor size compared with baseline according to RANO criteria for GBM/AA and RECIST 1.1 for NSCLC.

IV. To assess anti-tumor activity: intracranial and extracranial duration of response (DOR) and change in tumor size compared with baseline according to RANO criteria for GBM/AA and RECIST 1.1 for NSCLC.

V. To assess anti-tumor activity: intracranial and extracranial progression-free survival (PFS) and change in tumor size compared with baseline according to RANO criteria for GBM/AA and RECIST 1.1 for NSCLC.

EXPLORATORY/CORRELATIVE RESEARCH OBJECTIVES:

I. To investigate the presence and/or identity of the drug metabolites of WSD0922-FU, and the concentrations of these in the plasma, cerebrospinal fluid (CSF), and tumor.

II. To assess plasma concentration of WSD0922-FU and metabolite SN16110801P1 and pharmacokinetics (PK) parameters after single and multiple doses of WSD0922-FU.

III. To assess the brain tumor pharmacokinetics of WSD0922-FU and SN16110801P1 after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration [BTP] cohort only).

IV. To assess cerebrospinal fluid (CSF) concentration of WSD0922-FU and SN16110801P1 after multiple doses of WSD0922-FU (Dose Expansion - NSCLC leptomeningeal metastases [NSCLC LM] cohort only).

V. To explore the impact of tumor markers (e.g. MGMT promoter methylation, EGFR mutation [including EGFR vIII], PTEN deletion, TP53 mutation, etc.) on clinical parameters associated with WSD0922-FU treatment.

VI. To evaluate and measure pharmacodynamic biomarkers of inhibition of EGFR and downstream signals in tumor samples after a single dose of WSD0922-FU (Dose Expansion Cohort - BTP cohort only).

VII. To evaluate the effect of food on the pharmacokinetics of single dose of WSD0922-FU in plasma (Dose Expansion - NSCLC LM cohort only).

OUTLINE: This is a dose-escalation study.

DOSE ESCALATION: Patients receive WSD0922-FU orally (PO) once daily (QD) or twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

DOSE EXPANSION: Patients are assigned to 1 of 3 cohorts.

COHORT I: Patients with GBM/AA receive WSD0922-FU PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients with BTP receive a single dose of WSD0922-FU prior to surgery. Patients then undergo surgical resection of brain tumor. After surgery, patients receive WSD0922-FU PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

COHORT III: Patients with NSCLC LM receive WSD0922-FU PO on days 1 and 4 of cycle 0. Patients then receive WSD0922-FU PO BID on days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4-6 weeks, then every 2 months until progressive disease, at progressive disease, and then every 3 months after progressive disease for up to 5 years.

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