This phase I trial studies the side effects and best dose of WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung cancer that has spread to the central nervous system (central nervous system metastases). WSD0922-FU is a targeted treatment which blocks the EGFR protein - a strategy that has led to a lot of benefit in patients with many different cancers. WSD0922-FU may also be able to get into cancers in the brain and spinal cord and help patients with brain and spinal cord cancers.
Name: EGFR/EGFRvIII Inhibitor WSD0922-FU
Name: Therapeutic Conventional Surgery
Description: The RP2D is either the maximum tolerated dose (MTD) or the highest dose tested (in the case that none of the doses are deemed higher than the MTD), whichever is higher.
Measure: Recommended phase 2 dose Time: Up to 28 daysDescription: The overall response rate will be defined as the number of patients with a partial response (PR) or better that is confirmed in consecutive evaluations (at least 8 weeks apart) divided by the total number of evaluable patients. A 95% confidence interval will also be constructed using the properties of the binomial distribution.
Measure: Overall response rate Time: Up to 5 yearsDescription: Duration of response is defined as the number of days between a patient's first occurrence of a PR (or better) and progression. If a patient goes off study prior to progression (for another reason) then they will be censored at that time. A time to event analysis will be performed utilizing the Kaplan-Meier method which will yield a median DOR.
Measure: Duration of response (DOR) Time: From the first occurrence of a PR (or better) and progression, assessed up to 5 yearsDescription: A patient's progression free survival time is the number of days between study entry and disease progression. These data will be analyzed utilizing the Kaplan-Meier method which will yield a median PFS time.
Measure: Progression Free Survival (PFS) Time: From study entry to disease progression, assessed up to 5 yearsAllocation: Non-Randomized
Parallel Assignment
There are 5 SNPs
Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration - Any of the following cardiac criteria: - A marked baseline prolongation of QT/corrected QT (QTc) interval - (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fridericia's QT correction formula - A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) - The use of concomitant medications that prolong the QT/QTc interval - Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S) - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. --- T790M --- --- L858R --- --- C797S ---
Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A ---
Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R --- --- G719A ---
History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A ---
History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R --- --- G719A ---
Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R ---
Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R ---
Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration - Any of the following cardiac criteria: - A marked baseline prolongation of QT/corrected QT (QTc) interval - (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fridericia's QT correction formula - A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) - The use of concomitant medications that prolong the QT/QTc interval - Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S) - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. --- T790M --- --- L858R ---
Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration - Any of the following cardiac criteria: - A marked baseline prolongation of QT/corrected QT (QTc) interval - (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fridericia's QT correction formula - A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) - The use of concomitant medications that prolong the QT/QTc interval - Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S) - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. --- T790M --- --- L858R --- --- C797S --- --- L858R ---
History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R ---
History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R ---
Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q ---
Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R --- --- G719A --- --- L861Q ---
History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q ---
History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R --- --- G719A --- --- L861Q ---
Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration - Any of the following cardiac criteria: - A marked baseline prolongation of QT/corrected QT (QTc) interval - (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fridericia's QT correction formula - A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) - The use of concomitant medications that prolong the QT/QTc interval - Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S) - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. --- T790M ---