A Phase 1/2 Study Targeting Acquired Resistance Mechanisms in Patients with EGFR Mutant Non-Small Cell Lung Cancer - BLU-945-1101

Blueprint Medicines Corporation0 个研究点目标入组 6 人开始时间: 待定最近更新: 2024年4月15日

适应症

试验速览

阶段: 2 期
状态: 已完成
发起方: Blueprint Medicines Corporation
入组人数: 6

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional

入排标准

年龄范围: 18 至 99（—）

入选标准

•1. >=18 years of age at the time of signing the informed consent.
•2. Pathologically confirmed, definitively diagnosed, metastatic NSCLC harboring
•an activating EGFR mutation.
•3. Previously received at least 1 prior EGFR-targeted TKI with activity against
•the T790M mutation, such as osimertinib.
•a. Phase 1 Part 1B and Phase 2 Group 4: Patients must have experienced
•progressive disease while on osimertinib, were able to tolerate prior
•osimertinib 80 mg QD dose, and continuing on osimertinib is deemed to be in the
•patient*s best interests in the opinion of the Investigator. Patients who have
•discontinued osimertinib may be eligible if no more than 6 weeks elapse between
•the discontinuation of prior osimertinib and resumption of osimertinib on study.
•4. Tumor mutation profile determined locally via a Sponsor-approved testing
•methodology (NGS is preferred and will be required for Phase 2), using tumor
•tissue (ideally from a progressing lesion) and/or ctDNA in plasma. For Phase 1,
•it is preferable that samples used for analysis be obtained during or after
•disease progression on the last EGFR-targeted TKI received. For Phase 2,
•pre-treatment tumor sample must be obtained during or after disease progression
•on the last EGFR-targeted TKI received.
•a. Dose Escalation (Phase 1 Part 1A and Part 1B): At each dose level, slots may
•be reserved for patients with the mutations of interest.
•b. BLU-945 Monotherapy Expansion (Phase 2 Group 1, Group 2, and Group 3):
•Patients must have NSCLC harboring EGFR T790M and C797S mutation (Group 1);
•EGFR T790M but not C797S (Group 2); or EGFR C797S but not T790M (Group 3).
•c. BLU-945 with Osimertinib Expansion (Phase 2 Group 4): Slots may be reserved
•for patients with mutations of interest, but at least 12 slots will be
•allocated to patients with NSCLC harboring EGFR T790M and C797S mutation.
•5. Pretreatment tumor sample (either an archival sample or a sample obtained by
•pretreatment biopsy) submitted for central analysis. For Phase 1, it is
•preferable that pretreatment tumor samples be obtained from a progressing
•lesion, during or after disease progression on the last EGFR-targeted TKI
•received. For Phase 2, pre-treatment tumor sample must be obtained during or
•after disease progression on the last EGFR-targeted TKI received. Patients
•without appropriate archival tissue available, where biopsy is not considered
•safe and/or medically feasible, may be discussed with the study medical monitor
•and may be approved for enrollment on a case-by-case basis.
•6. Patients enrolled in Phase 1 Part 1A at doses expected to result in
•efficacious exposure levels (anticipated to be >=100 mg QD, but may be modified
•by the Sponsor based on emerging PK and clinical data) must consent to undergo
•on-treatment biopsy for central submission of tumor sample. Following approval
•from the Sponsor, on-treatment biopsy may be omitted for patients for whom the
•investigator does not feel that biopsy would be safe and/or feasible.
•Collection of these tumor samples may be discontinued for particular
•dose-escalation cohorts or expansion groups, if the Sponsor determines that
•adequate data have been obtained.
•7. Phase 2 Expansion Groups: Patient has at least 1 measurable target lesion
•evaluable by RECIST 1.1 as assessed by the investigator.
•8. Able to swallow an oral medicati

排除标准

•1. Tumor harbors any additional known driver alterations (including but not
•limited to EGFR exon 20 insertion, or pathologic abnormalities of KRAS, BRAF
•V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET).
•2. NSCLC with mixed cell histology or a tumor with histologic transformation
•(NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).
•3. Received the following anticancer therapy:
•a. EGFR-targeted TKI within 7 days prior to the first dose of study drug. Note:
•patients in Phase 1 Part 1B and Phase 2 Group 4 do not require a wash-out
•period for osimertinib.
•b. Any immunotherapy or other antibody therapy (including EGFR-targeted
•antibodies or bi-specific antibodies) within 28 days prior to the first dose of
•study drug (immune-related toxicities must have resolved to < Grade 2 prior to
•starting BLU 945).
•c. Any other systemic anticancer therapy within 14 days or 5 half-lives prior
•to the first dose of study drug, whichever is the shortest, but with a minimum
•of 7 days in all circumstances. BLU 945 may be started within these washout
•periods if considered by the Investigator to be safe and within the best
•interest of the patient, with prior Sponsor approval.
•d. Radiotherapy to a large field or including a vital organ (including whole
•brain radiotherapy or stereotactic radiosurgery to brain) within 14 days before
•the first dose of study drug. Participant received radiotherapy to a focal site
•of disease that did not include a vital organ (such as a limb) within 7 days
•before the first dose of study drug.
•4. CNS metastases or spinal cord compression that is associated with
•progressive neurological symptoms or requires increasing doses of
•corticosteroids to control the CNS disease. If a patient requires
•corticosteroids for management of CNS disease, the dose must have been stable
•for the 2 weeks preceding treatment. Asymptomatic CNS and leptomeningeal
•disease is allowed and, when measurable, should be captured as target lesions.
•5. Any of the following abnormalities on the most recent laboratory test prior
•to the first dose of study drug (ie, Cycle 1 Day 1 [C1D1] or screening):
•a. Absolute neutrophil count (ANC) <1.0×109/L.
•b. Platelet count <75×109/L.
•c. Hemoglobin <=8.0 g/dL (red blood cell transfusion and erythropoietin may be
•used to reach at least 8.0 g/dL, but must have been administered at least 2
•weeks prior to the first dose of study drug).
•d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× the
•upper limit of normal (ULN) if no hepatic metastases are present; >5× ULN if
•hepatic metastases are present.
•e. Total bilirubin >1.5× ULN; >3× ULN in presence of Gilbert*s disease.
•f. Estimated (Cockroft-Gault formula, Appendix 1) or measured creatinine
•clearance <40 mL/min.
•g. International normalized ratio (INR) >2.3 or prothrombin time (PT) >6
•seconds above control or a patient-specific INR or PT abnormality that the
•treating investigator considers clinically relevant and/or increases the risk
•for hemorrhage in that individual patient.
•6. Known intracranial hemorrhage and/or bleeding diatheses.
•7. Clinically active ongoing interstitial lung disease (ILD) of any etiology,
•including drug-induced ILD, and radiation pneumonitis within 28 days prior to
•initiation of study treatment. Patients with prior ILD associated with

研究者

发起方

Blueprint Medicines Corporation

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