A Phase IB/II, Open-Label, Multi-Center Study of EMB-01 Administered Intravenously in Combination with Osimertinib in Patients with Advanced/Metastatic EGFR-Mutant NSCLC
Details
This phase Ib/II trial studies the side effects and best dose of EMB-01 when given together with osimertinib in patients with EGFR-mutant non-small cell lung cancer that has spread to other places in the body (advanced or metastatic) and has progressed on standard treatment. EMB-01 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth in this type of cancer. EMB-01 in combination with osimertinib may work better in treating patients with EGFR-mutant advanced non-small cell lung cancer.
Eligibility
You can join if...
Inclusion Criteria:
-Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures
-Age ≥ 18 years
-ECOG ≤ 1
-Patients with histologically or cytologically confirmed advanced/metastatic EGFR-mutant NSCLC
-Patients must have measurable or evaluable disease per RECIST v1.1.
-Patients must be willing to submit a blood sample for gene alteration analysis by next generation sequencing (NGS).
-Archival tumor tissue (formalin-fixed paraffin-embedded) or a new biopsy is required prior to initiation of the study treatment for biomarker analysis.
-Phase Ib a. Patients who have progressed on/after standard therapy and no other therapies are available Phase II
-Total prior systemic therapy lines in the metastatic setting: ≤2 for Group 1, ≤3 for Group 2-3, ≤2 for Group 4.
Patients have progressed on/after a 3rd-generation EGFR TKI for Group 1-3; Patients have progressed on/after standard of care or other available treatment for Group 4. Note: For Group 4, a patient who has refused all currently available therapy is allowed to enroll, but this must be documented in the source record.
Group 1: Patient had a documented EGFR Exon 19del or L858R activating mutation and progressed while on osimertinib as first-line therapy in the advanced/metastatic setting.
Group 2: Patient has an EGFR T790M-persistent mutation, having progressed on/after 2nd- or later-line osimertinib or other 3rd-generation EGFR TKI.
Group 3: Patient had an EGFR T790M mutation, progressed on 2nd- or later-line osimertinib or another 3rd-generation EGFR TKI, and no longer harbors an EGFR T790M mutation.
Group 4: Patient has a documented EGFR Exon20ins activating mutation.
Exclusion Criteria:
-Life expectancy < 3 months
-Any remaining AE > grade 1 as per CTCAE v5.0 from prior anticancer therapy
-Patients with primary central nervous system (CNS) malignancy or symptomatic CNS metastases. Patients with CNS metastases are eligible if they do not need to receive local radiation treatment at the discretion of the Investigator or if radiation therapy for CNS metastases is completed ≥4 weeks prior to study treatment.
-Patients with a history of clinically significant cardiovascular disease including:
-Diagnosis of deep vein thrombosis or pulmonary embolism
-Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, may be eligible.
-Mean resting ECG QT-interval corrected according to Fridericia's formula (QTcF) > 470 milliseconds (ms) obtained from three ECGs, or clinically significant cardiac arrhythmia or electrophysiologic disease
-Baseline left ventricular ejection fraction (LVEF) ejection fraction below the lower limit of normal (LLN), as assessed by screening echocardiogram or multigated acquisition (MUGA) scan
-Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives
-History of primary immunodeficiency, stem cell or organ transplant, or previous clinical diagnosis of tuberculosis