NCT04857372进行中（未招募）1 期
An Open-label, Multi-center, Phase I Study of Oral IAG933 in Adult Patients With Advanced Mesothelioma and Other Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 137
- 试验地点
- 22
- 主要终点
- Number of patients with adverse events and serious adverse events
研究概览
简要总结
The purpose of this study is to characterize the safety and tolerability of IAG933 in patients with mesothelioma, NF2/LATS1/LATS2 mutated tumors and tumors with functional YAP/TAZ fusions and to identify the maximum tolerated dose and/or recommended dose.
详细描述
This is a phase I, open-label, multi-center study of IAG933 as a single agent consisting of a dose escalation part, followed by a dose expansion part. The escalation part will characterize the safety and tolerability. After the determination of the recommended dose/maximum tolerated dose, dose expansion will assess the preliminary anti-tumor activity in defined patient populations and further assess the safety and tolerability at RD/MTD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Male or female patients must be ≥ 18 years of age.
- •Dose escalation part: patients with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma or other solid tumors. Patients with solid tumors other than mesothelioma must have local available data for loss-of-function NF2/LATS1/LATS2 genetic alterations (truncating mutation or gene deletion; LATS1/LATS2 mutations will only be included in the dose escalation part), or functional YAP/TAZ fusions. Patients with malignant EHE can be enrolled with only histological confirmation of the disease. Patients must have failed available standard therapies, be intolerant of or ineligible for standard therapy, or for whom no standard therapy exists.
- •Dose expansion part: the following patients will be enrolled into 3 different treatment groups:
- •Group 1: Advanced (unresectable or metastatic) MPM patients who have failed available standard therapies for advanced/metastatic disease, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
- •Group 2: Advanced (unresectable or metastatic) solid tumor patients with available local data for NF2 truncating mutation or deletions. Patient must have failed available standard therapies, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
- •Group 3: Advanced (unresectable or metastatic) solid tumor patients with available local data for functional YAP/TAZ fusions. EHE patients can be included with only histological confirmation of the disease. Patient must have failed available standard therapies, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
- •Group 4: Advanced (unresectable or metastatic) non-pleural mesothelioma patients who have failed available standard therapies for advanced/metastatic disease, are intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
- •Presence of at least one measurable lesion according to mRECIST v1.1 for mesothelioma patients, RECIST v1.1 for patients with other solid tumors, or RANO for patients with primary brain tumors.
- •Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening/baseline, and again during therapy on this study. An archival tumor sample may be used at screening. During the dose expansion part of the study, a decision may be made to stop the collection of on-treatment biopsies.
排除标准
- •Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
- •≤ 4 weeks for thoracic radiotherapy to lung fields or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment. An exception to this exists for patients who have received palliative radiotherapy to bone, who must have recovered from radiotherapy-related toxicities but for whom a 2-week washout period is not required.
- •≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.
- •≤3 weeks for treatment with cytotoxic agents or ≤ 6 weeks for cytotoxic agents with risk of major delayed toxicities, such as nitrosoureas and mitomycin C.
- •≤ 4 weeks for immuno-oncologic therapy, such as CTLA4, PD-1, or PD-L1 antagonists
- •Prior treatment with TEAD inhibitor at any time
- •For mesothelioma patients: use of non-invasive antineoplastic therapy (e.g., tumor treating fields, brand name Optune LuaTM) within 2 weeks of the tumor assessment at screening.
- •Malignant disease, other than that being treated in this study.
- •Insufficient renal function at Screening.
- •Clinically significant cardiac disease or risk factors at screening
- •Insufficient bone marrow function at screening.
- •Insufficient hepatic function at screening.
- •Patients who have the following laboratory values > Common Terminology Criteria for Adverse Events (CTCAE) grade 1:
- •Total calcium (corrected for low serum albumin)
- •Known active COVID-19 infection.
- •Pregnant or nursing (lactating) women,
- •Japan only: patients with a history of drug- and/or non-drug-induced interstitial lung disease (ILD) ≥ Grade
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Group 1
Experimental
Malignant pleural mesothelioma
干预措施: IAG933 (Drug)
Group 2
Experimental
NF2 truncating mutations or deletions
干预措施: IAG933 (Drug)
Group 3
Experimental
Solid tumors with functional YAP/TAZ fusions
干预措施: IAG933 (Drug)
Group 4
Experimental
Non-pleural mesothelioma
干预措施: IAG933 (Drug)
结局指标
主要结局
Number of patients with adverse events and serious adverse events
时间窗: 3 years
Safety and tolerability of IAG933
Number of patients with dose interruptions and dose changes
时间窗: 3 years
Tolerability of IAG933
Incidence of dose limiting toxicities during the first treatment cycle (dose escalation only)
时间窗: 1 year
Safety, tolerability and the maximum tolerated dose or recommended dose of IAG933
次要结局
- Progression free survival (PFS)(3 years)
- Overall response rate (ORR)(3 years)
- Maximum serum concentration (Cmax)(3 years)
- Half life (T1/2) (dose escalation only)(1 year)
- Disease control rate (DCR)(3 years)
- Time to reach Cmax (Tmax)(3 years)
- Area under the curve (AUC)(3 years)
- Duration of response (DOR)(3 years)
- Minimum serum concentration (Cmin) (dose escalation only)(1 year)
- Overall survival (OS) (dose expansion only)(3 years)
- Accumulation ratio (Racc) (dose escalation only)(1 year)
研究者
研究点 (22)
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相关资讯
Novartis' IAG933 Shows Promise in Advanced Solid Tumors with Specific Genetic Alterations• A Phase I study evaluates IAG933, a TEAD inhibitor, in patients with advanced mesothelioma or other solid tumors harboring NF2/LATS1/LATS2 alterations or YAP/TAZ fusions.
• The trial includes dose escalation and expansion phases to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of IAG933.
• Enrollment focuses on patients who have exhausted standard therapies, are ineligible for them, or lack standard treatment options, indicating a high unmet need.
• The study mandates tumor biopsies to monitor treatment response and explore potential biomarkers, enhancing understanding of IAG933's mechanism.last yearIAG933, a Novel YAP/TAZ-TEAD Inhibitor, Shows Promise in Preclinical Cancer Models• IAG933 directly disrupts the YAP/TAZ-TEAD protein-protein interaction, leading to YAP eviction from chromatin and reduced Hippo-mediated transcription.
• In preclinical models, IAG933 demonstrates deep tumor regression in Hippo-driven mesothelioma xenografts and shows efficacy in combination with other inhibitors in lung, pancreatic, and colorectal cancer.
• The inhibitor exhibits potent antiproliferative activity in Hippo-dependent cell lines, particularly mesothelioma, and demonstrates a more rapid and profound reduction in cell viability compared to allosteric TEAD inhibitors.
• Clinical evaluation of IAG933 is currently underway, marking a significant step in exploring its potential as a therapeutic agent for various solid tumors.2 years agoFirst Patient Dosed in Trial of TEAD Inhibitor for Advanced Solid Tumors• A Phase 1/2 clinical trial (NCT04857372) has dosed its first patient to evaluate a TEAD inhibitor in advanced solid tumors, including mesothelioma.
• The trial includes patients with mesothelioma, NF2-mutated tumors, and YAP/TAZ fusion-positive cancers who have exhausted standard therapies.
• The study will assess the safety, tolerability, and preliminary efficacy of the TEAD inhibitor through dose escalation and expansion phases.
• Enrollment is open to patients 18 years and older with measurable lesions and willingness to undergo tumor biopsies.4 years ago