A PHASE 1 OPEN-LABEL STUDY OF HER3-DXd (PATRITUMAB DERUXTECAN; U3-1402) IN COMBINATION WITH OSIMERTINIB IN SUBJECTS WITH LOCALLY ADVANCED OR METASTATIC EGFR-MUTATED NON-SMALL CELL LUNG CANCER (NSCLC)

Inoguchi Akihiro0 个研究点目标入组 280 人开始时间: 2020年12月15日最近更新: 2024年4月23日

适应症

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 280

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: >= 18age old 至 ot applicable（—）
性别: All

入选标准

•Inclusion Criteria Specific to Dose Escalation and Second-Line Dose Expansion:
•-Documentation of EGFR exon 19 deletion or L858R mutation detected from tumor tissue
•-Must have received osimertinib for locally advanced or metastatic disease at a dose of 80 mg QD for at least 6 weeks and must not miss more than two doses during the 2 weeks prior to the first day of study treatment (Cycle 1, Day 1)
•-Must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting
•-Has documentation of radiological disease progression following first-line treatment with osimertinib in the locally advanced or metastatic setting
•Inclusion Criteria Specific to First-Line Dose Expansion:
•-The tumor tissue harbors one of the 2 common EGFR mutations occurring in NSCLC known to be associated with EGFR-TKI sensitivity (exon 19 deletion or L858R) as assessed by Clinical Laboratory Improvement Amendments (CLIA)-certified (US sites), accredited (outside of the US), local laboratory or central laboratory. Only tissue-basedtesting will be accepted.
•-Subjects must have previously untreated locally advanced or metastatic NSCLC and must be eligible to receive first-line treatment with osimertinib, according to the judgment of the investigator. Prior adjuvant or neo-adjuvant therapy (chemotherapy, radiotherapy, investigational agents; except with osimertinib) is permitted.
•Common Inclusion Criteria For All Subjects:
•-Male or female subjects aged >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
•-Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation
•-At least 1 measurable lesion as assessed by investigator assessment according to RECIST v1.1
•-Tissue requirements
•a. Dose Escalation (all cohorts): provide an optional pre-treatment tumor tissue of sufficient quantity, as defined in the laboratory manual. The optional pre-treatment tumor tissue can be provided as either:
•-Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy.
•-Archival tissue collected from a biopsy performed prior to signing of the tissue consent, and since progression while on treatment with the most recent cancer therapy regimen.
•b. First-line Dose Expansion (Cohorts 3, 4a, and 4b): provide an optional pre-treatment and optional on-treatment tumor tissues of sufficient quantity, as defined in the laboratory manual. The optional pre-treatment tumor tissue can be provided as either:
•-Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy.
•-Archival tissue collected from a biopsy performed at the time of the initial diagnosis or later
•c. Second-line Dose Expansion (Arm 1, Arm 1b, and Arm 2): provide a required pre-treatment and required on-treatment tumor tissues of sufficient quantity, as defined in the laboratory manual. The required pre-treatment tumor tissue can be provided as either:
•-Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy.
•-Archival tissue collected from a biopsy performed prior to signing of the tissue consent, and since progression while on treatment with the most recent cancer therapy regimen
•-Has adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1 defined as:
•Platelet count: >=100 000/mm3 or >=100 x 109/L (platelet tr

排除标准

•-Any previously documented histologic or cytologic evidence of small cell OR combined small cell/non small cell disease
•-Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening
•-Clinically severe pulmonary compromise (based on Investigator`s assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
•a. any underlying pulmonary disorder (eg, pulmonary emboli within three months of the study enrollment or randamization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, or pleural effusion)
•b. any autoimmune, connective tissue or inflammatory disorder with pulmonary
•involvement (eg, rheumatoid arthritis, Sjogren's syndrome, or sarcoidosis)
•OR prior complete pneumonectomy
•-Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1, Day 1. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
•-Evidence of any leptomeningeal disease
•-Has spinal cord compression or clinically active central nervous system metastases, defined as symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study. Note: A CT or MRI scan of the brain at baseline is required for all subjects.
•Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study.
•-Inadequate washout period prior to Cycle 1, Day 1 (Dose Escalation and First-Line Dose Expansion) or prior to randomization (Second-Line Dose Expansion) defined as:
•a. Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days
•b. Any systemic anticancer (excluding osimertinib in all Dose Escalation cohorts and in Second-Line Dose Expansion [Arms 1, 2, and 1b]), including investigational agents, <14 days or 5 half-lives, whichever is longer
•c. Immune checkpoint inhibitor therapy <5 half-lives
•d. Major surgery (excluding placement of vascular access) <4 weeks
•e. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation < 28 days or palliative radiation therapy <14 days
•f. Chloroquine or hydroxychloroquine <=14 days
•g. Medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 < 21 days.
•-Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, Grade <=1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.
•-Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow osimertinib, or previous significant bowel resection that would preclude adequate absorption of osimertinib
•-Has any primary malignancy other than locally advanced or

研究者

发起方

Inoguchi Akihiro

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