A Multicenter, Open-label, Phase 1/1b / Phase 2 Dose Finding, Safety, and Pharmacokinetic Study of MBRC-101, an Anti-EphA5 Monomethyl Auristatin E (MMAE) Antibody Drug Conjugate, in Advanced Refractory Solid Tumors

MBrace Therapeutics17 个研究点分布在 1 个国家目标入组 130 人2023年11月7日

适应症Cancer

干预措施Antibody-Drug Conjugate

概览

阶段: 1 期
干预措施: Antibody-Drug Conjugate
疾病 / 适应症: Cancer
发起方: MBrace Therapeutics
入组人数: 130
试验地点: 17
主要终点: Occurrence of treatment-emergent adverse events (TEAEs)
状态: 招募中
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is a first-in-human (FIH), open label Phase 1/1b / Phase 2 study in patients with advanced metastatic solid tumors refractory to standard treatment. Phase 1 will identify potential optimal biologically relevant doses (OBRD) and the maximum tolerated dose (MTD) of MBRC-101 at one 1 or more dosing regimens. Phase 1b will evaluate the safety and preliminary clinical activity of MBRC-101 at potential OBRDs. Phase 1 and Phase 1b will both characterize single and multiple-dose PK profiles and evaluate incidence and persistence of anti-MBRC-101 Ab. Phase 2 will evaluate the efficacy of MBRC-101 at the RP2D from Phase1b.

详细描述

Phase 1, dose escalation, will enroll approximately 30 patients with advanced or metastatic solid tumors refractory to standard therapy. EphA5 expression will not be required for enrollment into Phase 1 but will be assessed retrospectively. Phase1b, the dose expansion phase will evaluate the safety and preliminary clinical activity of MBRC-101 at potential OBRDs and dosing regimens in patients with advanced or metastatic solid tumors refractory to standard therapy. Phase 1b will enroll 3 expansion cohorts of ≈ 20 patients per cohort (n ≈ 60 total). The Phase 2 portion will begin when the RP2D has been determined from Phase 1b and all Phase 1b patients have completed at least two cycles of treatment or have discontinued from the study prior to completing two cycles of treatment. Phase 2 will evaluate anti-tumor activity and safety of the RP2D determined during Phase 1b. Phase 2 will focus on a specific tumor type identified during Phase 1/1b and will enroll approximately 30 patients. Safety will be monitored by the Safety Review Committee (SRC) at each dose escalation in Phase 1 and at regular intervals throughout Phase 1b and Phase 2. Overall Response Rate (ORR), Progression Free Survival (PFS), Response Rate (RR), Overall Survival (OS), Disease Control Rate (DCR), and Complete and Partial response (CR and PR) will be used to evaluate efficacy per RECIST v1.1 criteria based on the results of positron emission tomography and computed tomography (PET-CT), computerized tomography (CT), and magnetic resonance imaging (MRI) scans.

注册库

clinicaltrials.gov

开始日期

2023年11月7日

结束日期

2026年11月1日

最后更新

2个月前

研究类型

Interventional

研究设计

Sequential

性别

All

研究者

发起方

MBrace Therapeutics

责任方

Sponsor

入排标准

入选标准

•Provide written consent on an Informed Consent Form (ICF), approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to any study-specific evaluation. Patients should have the ability to read and understand the ICF, ask for any clarifications from the study staff, and be able to comply with all planned study procedures.
•18 years of age or older at the time of informed consent.
•Female patients must be at least 2 years postmenopausal (defined as 2 years without menses), surgically sterile (at least 6 months prior to dosing; must be documented) or practicing effective contraception (must agree to use 2 forms of contraception, 1 of which must be a barrier method) and willing to continue to use effective contraception for the duration of study participation and for 6 months after the final dose of study drug. Female patients must be nonlactating and have a negative serum pregnancy test result at screening and baseline.
•Male patients must agree to use effective contraception (must agree to use 2 forms of contraception, 1 of which must be a barrier method) for the duration of study participation and for 6 months after the final dose of study drug.
•Have a histologic or cytologic diagnosis of malignant solid tumor for which there are no standard of care treatment options known to confer a clinical benefit or for which the patient is ineligible or declines.
•A. For Phase 1 dose escalation: histologic or cytologic diagnosis of malignant solid tumor of any type. The Sponsor may remove specific tumor indications based on emerging, real-time study data.
•B. For Phase 1b dose expansion:
•i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).
•ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2 negative breast cancer.
•iii. Cohort C: Histologic or cytologic diagnosis of the following advanced metastatic solid tumors refractory to standard treatment: pancreatic adenocarcinoma, gastric adenocarcinoma, hepatocellular carcinoma, ovarian adenocarcinoma, and squamous cell carcinoma including, but not limited to, primary malignancies of the head and neck, esophagus, cervix, and skin. The Sponsor may add or remove specific tumor indications based on emerging, real-time study results.

排除标准

•Preexisting sensory neuropathy Grade ≥
•Preexisting motor neuropathy Grade ≥
•Uncontrolled central nervous system metastases.
•Use of any investigational drug within 14 days prior to the first dose of study drug.
•Any anticancer therapy within 14 days prior to the first dose of study drug, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy, or any other agents to treat cancer (anti-hormonal therapy given for advanced prostate cancer or as adjuvant therapy for early stage, hormone receptor (HR) positive breast cancer is not considered cancer therapy for the purpose of this Protocol).
•Strong CYP3A or inducers within 14 days prior to the first dose of study drug.
•Thromboembolic events and/or bleeding disorders 14 days (e.g., venous thromboembolism \[VTE\] or pulmonary embolism \[or PE\]) prior to the first dose of study drug.
•8\. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class 3-4 within 6 months prior to the first dose of MBRC-
•9\. A baseline QT (time from the beginning of the Q wave to the end of the T wave) interval as corrected by Fridericia's formula (QTcF) \> 470 msec.
•10\. Human immunodeficiency virus (HIV) infection with 1 or more of the following: A. Acquired immunodeficiency syndrome (AIDs)-defining opportunistic infection within 6 months of the start of screening; B. A change in antiretroviral therapy within 3 months of the start of screening and viral load \> 500 copies/mL; C. Receiving antiretroviral therapy that may interfere with study drug; D. CD4 count \< 350 at screening.