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

February 2, 2024 updated by: Mayo Clinic

Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of WSD0922-FU

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.

Funding Source - FDA OOPD

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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 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 - GBM/AA 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 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.

All patients also undergo computed tomography (CT) scans, magnetic resonance imaging (MRI), and collection of blood and CSF (NSCLC only) samples throughout the trial.

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.

Study Type

Interventional

Enrollment (Estimated)

51

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic in Arizona
        • Contact:
        • Principal Investigator:
          • Maciej M. Mrugala, M.D., Ph.D.
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Recruiting
        • Mayo Clinic in Florida
        • Principal Investigator:
          • Kurt A. Jaeckle, M.D.
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
        • Principal Investigator:
          • Sani H. Kizilbash, M.D., M.P.H.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort
  • Histolopathological and/or molecular confirmation of either glioblastoma, IDH wildtype (GBM), (as defined by either the 2016 or 2021 World Health Organization [WHO] classifications) anaplastic astrocytoma, IDH wildtype (AA) (as defined by the 2016 WHO classification) or non-small cell lung cancer (NSCLC)

  • EGFR Status:

    • GBM/AA must either EGFR amplification and/or any activating EGFR mutation (e.g. A289T, EGFRvIII , etc.)
    • NSCLC must have a confirmed activating EGFR mutation (e.g. Del19, L858R, EGFRvIII, G719A, L861Q, T790M, C797S, etc.)
  • Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts

  • Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort:

    • Diagnosis: Histological or molecular confirmation of either glioblastoma, IDH wildtype (GBM) (as defined by either the 2016 or 2021 WHO classifications) or anaplastic astrocytoma, IDH wildtype (AA) (as defined by the 2016 WHO classification)
    • EGFR status: GBM/AA must have EGFRvIII mutation

  • Brain Tumor Penetration (BTP) Cohort:

    • Diagnosis: Histopathological or molecular confirmation of either glioblastoma, IDH wildtype (GBM) (as defined by either the 2016 or 2021 WHO classifications) or anaplastic astrocytoma, IDH wildtype (AA) (as defined by the 2016 WHO classification)
    • EGFR status: GBM/AA must have been previously demonstrated to have either EGFR amplification and/or any activating EGFR mutation based on any prior resection

  • Non-Small Cell Lung Cancer (NSCLC) cohort:

    • Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) • EGFR status: NSCLC must have confirmed activating EGFR mutation
  • 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. gefitinib, erlotinib, afatinib, or osimertinib)

  • Radiographic progression:

    • Patients with GBM/AA must have radiographic progression based on RANO criteria
    • Patients with NSCLC must have new or radiographic progression in the central nervous system (brain metastases and/or leptomeningeal metastases). Positive confirmation of CSF cytology is both necessary and sufficient to define the presence of leptomeningeal metastases for patients in this study. Patients with positive CSF cytology and brain metastases will be categorized as "leptomeningeal metastases."
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) 0 or 1. For patients with NSCLC with leptomeningeal metastases, ECOG 2 is also acceptable
  • Registration - Inclusion Criteria Specific to Dose Expansion Cohorts

  • Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort:

    • Previous treatments: Patients must have been previously treated with radiation and temozolomide. First recurrence only (no additional systemic therapies have been administered for recurrent disease)
    • Radiographic progression: Patients with GBM/AA must have radiographic progression based on RANO criteria
    • Measurable disease
    • Performance status: ECOG 0 or 1 for patients with GBM/AA

  • Brain Tumor Penetration (BTP) Cohort:

    • Previous treatments: Patients must have been previously treated with radiation and temozolomide
    • Radiographic progression: Patients with GBM/AA must have radiographic progression based on RANO criteria
    • Therapeutic surgical resection of GBM/AA required as part of routine clinical care
    • Performance status: ECOG 0 or 1

  • Non-Small Cell Lung Cancer (NSCLC) cohort:

    • Previous treatments: No limitations
    • Radiographic progression: Patients must have new or radiographic progression in the central nervous system (brain metastases and/or leptomeningeal metastases). Positive confirmation of CSF cytology is both necessary and sufficient to define the presence of leptomeningeal metastases for patients in this study. Patients with positive CSF cytology and brain metastases will be categorized as "leptomeningeal metastases."
    • Measurable Disease
    • Performance Status: ECOG 0 or 1
  • Registration - Inclusion Criteria Common to Dose Escalation and Dose Expansion Cohorts:
  • Age >= 18 years old
  • Ability to understand and the willingness to sign a written informed consent document
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • Leukocytes >= 3.0 x 10^9/L (obtained =< 14 days prior to registration)
  • Absolute neutrophil count >= 1.5 x 10^9/L (obtained =< 14 days prior to registration)
  • Platelets >= 100 x 10^9/L (obtained =< 14 days prior to registration)

  • International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)

    • Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/prothrombin time (PT) and partial thromboplastin time (PTT)/activated (a)PTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion

  • aPTT =< 1.5 x ULN (obtained =< 14 days prior to registration)

    • Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion
  • Total bilirubin =< 1.5 x ULN and =< 3 mg/dL for patients with Gilbert's disease (obtained =< 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN or =< 5 x ULN if due to liver involvement by tumor (obtained =< 14 days prior to registration)
  • Creatinine =< 1.5 x ULN or estimated glomerular filtration rate (estimated glomerular filtration rate [eGFR]) >= 60 mL/minute (obtained =< 14 days prior to registration)
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Provision of signed and dated written informed consent prior to any study specific procedures, sampling, and analyses
  • Willingness to provide mandatory blood specimens for correlative research
  • Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study i.e., active treatment and clinical follow-up)
  • Male and female patients of child bearing potential must be willing to use contraception, (i.e., condoms, birth control) while on study and until 3 months after the last dose of study drug is taken
  • Must be willing to take light-protective measures during the study and for 2 weeks after their last dose of WSD0922-FU
  • Must have a minimum life expectancy of >= 3 months
  • Must be stable on no more than 2 mg of dexamethasone (or equivalent steroids) per day. Steroid dose adjustments should be minimized during cycle 1 of therapy
  • Must not take enzyme-inducing anticonvulsants treatment for at least 2 weeks prior to enrollment. Patients on enzyme-inducing anticonvulsants will be changed to non-enzyme inducing anticonvulsants
  • Strong inducers and strong inhibitors of CYP3A should be discontinued at least 14 days prior to registration
  • Willingness to provide mandatory tissue specimens for correlative research (BTP cohort only)

Exclusion Criteria:

  • Registration - Exclusion Criteria for Dose Escalation and Dose Expansion

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception

  • Any of the following prior therapies:

    • Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen =< 14 days prior to registration
    • In patients with NSCLC, treatment with an EGFR TKI (e.g., erlotinib, gefitinib, afatinib or osimertinib) within 8 days or approximately 5 x half-life, whichever is the longer, prior to registration (if sufficient wash-out time has not occurred due to schedule or PK properties, an alternative appropriate wash-out time based on known duration and time to reversibility of drug related adverse events could be agreed upon by the Investigator and Wayshine)
    • Radiation therapy to the brain =< 12 weeks prior to registration
    • Patients with GBM/AA must not have received (i) nitrosoureas within 42 days of registration, (ii) any chemotherapy or experimental therapy within 28 days or 5 half-lives, whichever is longer, prior to registration
    • Patients with GBM/AA must not have received prior anti-EGFR or EGFRvIII therapies (erlotinib, gefitinib, afatinib, osimertinib, ABT-414, ABBV-221, AMG-595, AMG-596 etc.)
    • Patients with GBM/AA who have been treated with bevacizumab within the last four months are not eligible
    • Received prior systemic biologic therapy (CAR-T, anti-PD-1 / anti-PD-L1, anti-CTLA-4, etc.) within 28 days prior to registration.
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required
  • Subjects who are human immunodeficiency virus (HIV), hepatitis virus B (HBV), and/or hepatitis virus C (HCV) positive

  • Uncontrolled inter-current illness including, but not limited to:

    • Symptomatic CNS complications that require urgent neurosurgical or medical (e.g. mannitol) intervention
    • Seizures requiring a change in anti-epileptic medications (addition of new anti-epileptic or increase in dose) =< 2 weeks of registration
    • Known intracranial hemorrhage which is unrelated to tumor
    • Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol
    • Illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers and carcinoma-in-situ of the cervix. 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. 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
  • Patients who are unable to tolerate dairy (GBM/AA cohort only). This is to ensure that patients on this cohort can participate in the food effect study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose escalation (WSD0922-FU)
Patients receive WSD0922-FU PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans, MRI, and collection of blood samples throughout the trial.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU
Procedure: Biospecimen Collection
Undergo collection of CSF samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Experimental: Dose expansion Cohort I (WSD0922-FU)
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. Patients also undergo CT scans, MRI, and collection of blood samples throughout the trial.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU
Procedure: Biospecimen Collection
Undergo collection of CSF samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Experimental: Dose expansion Cohort II (WSD0922-FU, surgery)
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. Patients also undergo CT scans, MRI, and collection of blood samples throughout the trial.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Procedure: Therapeutic Conventional Surgery
Undergo surgical resection
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU
Procedure: Biospecimen Collection
Undergo collection of CSF samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Experimental: Dose expansion Cohort III (WSD0922-FU)
Patients with NSCLC 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. Patients also undergo CT scans, MRI, and collection of blood and CSF samples throughout the trial.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
Given PO
Other Names:
  • BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU
  • EGFR Mutant Inhibitor WSD0922-FU
  • WSD 0922-FU
  • WSD-0922-FU
  • WSD0922-FU
Procedure: Biospecimen Collection
Undergo collection of CSF samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended phase 2 dose
Time Frame: Up to 28 days
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.
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 4-6 weeks after study completion
Up to 4-6 weeks after study completion
Duration of response (DOR)
Time Frame: From the first occurrence of a PR (or better) and progression, assessed up to 5 years
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.
From the first occurrence of a PR (or better) and progression, assessed up to 5 years
Progression Free Survival (PFS)
Time Frame: From study entry to disease progression, assessed up to 5 years
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.
From study entry to disease progression, assessed up to 5 years
Overall response rate
Time Frame: Up to 5 years
The overall response rate will be defined as the number of patients with a partial response (PR) or complete response (CR) 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.
Up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proteomic analysis
Time Frame: Up to 5 years
Partial least squares regression will be used to perform unbiased correlations of network-level signaling data acquired from patient samples with patient phenotypic data or to drug distribution data.
Up to 5 years
Pharmacokinetic (PK) analysis (Dose escalation cohort) - AUCs
Time Frame: Day 1 Cycle 1 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Day 1 Cycle 1 (each cycle is 28 days)
Pharmacokinetic (PK) analysis (Dose escalation cohort) - AUCs
Time Frame: D15 Cycle 1 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
D15 Cycle 1 (each cycle is 28 days)
Pharmacokinetic (PK) analysis (Dose escalation cohort) - AUCs
Time Frame: D1 Cycle 2 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
D1 Cycle 2 (each cycle is 28 days)
Pharmacokinetic (PK) analysis (Dose escalation cohort) - AUCs
Time Frame: Pre-dose at end of study (EOS) - each cycle is 28 days
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Pre-dose at end of study (EOS) - each cycle is 28 days
Pharmacokinetic (PK) analysis (Dose escalation cohort) - Clearance (CL)
Time Frame: Day 1 Cycle 1 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Day 1 Cycle 1 (each cycle is 28 days)
Pharmacokinetic (PK) analysis (Dose escalation cohort) - Clearance (CL)
Time Frame: D15 Cycle 1 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
D15 Cycle 1 (each cycle is 28 days)
Pharmacokinetic (PK) analysis (Dose escalation cohort) - Clearance (CL)
Time Frame: D1 Cycle 2 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
D1 Cycle 2 (each cycle is 28 days)
Pharmacokinetic (PK) analysis (Dose escalation cohort) - Clearance (CL)
Time Frame: Pre-dose at end of study (EOS) - each cycle is 28 days
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose at end of study (EOS) - each cycle is 28 days
PK analysis (Cohort I) - AUC
Time Frame: D1 of cycles 1 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
D1 of cycles 1 (each cycle is 28 days)
PK analysis (Cohort I) - AUC
Time Frame: D1 of cycle 2 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
D1 of cycle 2 (each cycle is 28 days)
PK analysis (Cohort I) - Clearance (CL)
Time Frame: Pre-dose D1 of cycles 3 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose D1 of cycles 3 (each cycle is 28 days)
PK analysis (Cohort I) - Clearance (CL)
Time Frame: Pre-dose D1 of cycles 4 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose D1 of cycles 4 (each cycle is 28 days)
PK analysis (Cohort II) - AUC
Time Frame: Day 1 of cycle 0
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Day 1 of cycle 0
PK analysis (Cohort II) - AUC
Time Frame: Pre-dose D1 of cycles 3 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Pre-dose D1 of cycles 3 (each cycle is 28 days)
PK analysis (Cohort II) - AUC
Time Frame: Pre-dose D1 of cycles 4 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Pre-dose D1 of cycles 4 (each cycle is 28 days)
PK analysis (Cohort II) - Clearance (CL)
Time Frame: Day 1 of cycles 1 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Day 1 of cycles 1 (each cycle is 28 days)
PK analysis (Cohort II) - Clearance (CL)
Time Frame: Day 1 of cycles 2 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Day 1 of cycles 2 (each cycle is 28 days)
PK analysis (Cohort II) - Clearance (CL)
Time Frame: Pre-dose day 1 of cycles 3 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose day 1 of cycles 3 (each cycle is 28 days)
PK analysis (Cohort II) - Clearance (CL)
Time Frame: Pre-dose day 1 of cycles 4 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose day 1 of cycles 4 (each cycle is 28 days)
PK analysis (Cohort III) - AUC
Time Frame: Days 1 and 4 of cycles 0
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Days 1 and 4 of cycles 0
PK analysis (Cohort III) - AUC
Time Frame: Day 1 of cycle 2 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Day 1 of cycle 2 (each cycle is 28 days)
PK analysis (Cohort III) - AUC
Time Frame: Pre-dose day 1 of cycles 3 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Pre-dose day 1 of cycles 3 (each cycle is 28 days)
PK analysis (Cohort III) - AUC
Time Frame: Pre-dose day 1 of cycles 4 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under curves (AUCs) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics, AUC will then be tested for association changes in responses.
Pre-dose day 1 of cycles 4 (each cycle is 28 days)
PK analysis (Cohort III) - Clearance (CL)
Time Frame: Days 1 and 4 of cycles 0
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Days 1 and 4 of cycles 0
PK analysis (Cohort III) - Clearance (CL)
Time Frame: D1 of cycle 2 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
D1 of cycle 2 (each cycle is 28 days)
PK analysis (Cohort III) - Clearance (CL)
Time Frame: Pre-dose day 1 of cycles 3 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose day 1 of cycles 3 (each cycle is 28 days)
PK analysis (Cohort III) - Clearance (CL)
Time Frame: Pre-dose day 1 of cycles 4 (each cycle is 28 days)
A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual clearance (CL) of WSD0922. The pharmacokinetic will be evaluated by the model, along with other participant factors that may explain the inter-participant variability in pharmacokinetics,as well as the observed Cmax, will then be tested for association changes in responses.
Pre-dose day 1 of cycles 4 (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Sani H. Kizilbash, M.D., M.P.H., Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2019

Primary Completion (Estimated)

December 20, 2024

Study Completion (Estimated)

December 20, 2024

Study Registration Dates

First Submitted

November 25, 2019

First Submitted That Met QC Criteria

December 11, 2019

First Posted (Actual)

December 13, 2019

Study Record Updates

Last Update Posted (Estimated)

February 5, 2024

Last Update Submitted That Met QC Criteria

February 2, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC1914 (Other Identifier: Mayo Clinic in Rochester)
  • P30CA015083 (U.S. NIH Grant/Contract)
  • NCI-2019-07825 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • R01FD007288 (U.S. FDA Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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