NCT02912949进行中（未招募）2 期
A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors (eNRGy)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 250
- 试验地点
- 62
- 主要终点
- Objective overall response rate (ORR) as per local investigator's assessment
研究概览
简要总结
This is a Phase I/II, open-label, multi-center, multi-national, dose escalation, single agent study to assess the safety, tolerability, PK, PD, immunogenicity and anti-tumor activity of zenocutuzumab (MCLA-128) in patients with solid tumors harboring an NRG1 fusion (eNRGy)
详细描述
Study Design :
This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consisting of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed.
Part 2 new patient populations examine:
- Group F: Patients with NSCLC with documented NRG1 fusion
- Group G: Patients with pancreatic adenocarcinoma with documented NRG1 fusion
For these new patient populations, Part 2 will further characterize the safety and tolerability of the selected dose level of zenocutuzumab (MCLA-128), as well as assessment of CBR, defined as the proportion of patients with a CR, PR or durable SD (SD for at least 24 weeks in duration). For the new patient populations, overall response rate (ORR) and duration of response (DOR) will be described.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 15) in Group H;
- •Performance status of ECOG 0 - 2;
- •Estimated life expectancy of at least 12 weeks;
- •Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1;
- •Treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of MCLA-128:
- •more than 14 days or more than 5 half-lives prior to study entry, whichever is shorter.
- •more than 14 days for radiotherapy.
- •Recovery from major surgery or other complication to ≤ Grade 2 or baseline ;
- •Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support for at least 7 days prior to screening;
- •Platelets ≥75 x 109/L without transfusion support for at least 7 days prior to screening;
- •Hemoglobin ≥8 g/dL or ≥5 mmol/L;
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN; in cases of metastatic liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed; in cases of antecedents of Gilbert's syndrome when total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN will be allowed;
- •Estimated glomerular filtration rate (GFR) of more than 30 mL/min
- •Able to provide a tumor biopsy sample (fresh strongly preferred or else archival);
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for 6 month after completion of study therapy;
- •Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy or no satisfactory alternative treatment options are available;
- •Locally-advanced unresectable or metastatic solid tumor malignancy with documented NRG1 gene fusion, identified through molecular assays such as next generation sequencing-based assays [DNA or RNA], as routinely performed at CLIA or other similarly-certified laboratories.
排除标准
- •Pregnant or lactating;
- •Presence of an active uncontrolled infection or an unexplained fever;
- •Known hypersensitivity to any of the components of MCLA-128;
- •Known HIV, active Hepatitis B without receiving antiviral treatment, or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible
- •Known symptomatic or unstable brain metastases;
- •Patients with leptomeningeal metastases;
- •Presence of LVEF below 50% on the screening echocardiogram; or history or presence of any significant cardiovascular disease, including unstable angina or myocardial infarction within 12 months prior to screening, congestive heart failure (NYHA Class III or IV), or ventricular arrhythmia requiring medication;
- •Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2 years prior to study entry;
- •Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.
研究组 & 干预措施
Part 2 NSCLC cancer harboring NRG1 fusion
Experimental
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
干预措施: zenocutuzumab (MCLA-128) (Drug)
Part 2 Pancreatic adenocarcinoma harboring NRG1 fusion
Experimental
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
干预措施: zenocutuzumab (MCLA-128) (Drug)
Part 2 Solid tumour (basket) harboring NRG1 fusion
Experimental
Participants will receive intravenous infusion of 750 mg of zenocutuzumab (MCLA-128) (the recommended Phase 2 dose (RP2D)) every 2 weeks.
干预措施: zenocutuzumab (MCLA-128) (Drug)
结局指标
主要结局
Objective overall response rate (ORR) as per local investigator's assessment
时间窗: 36 months
Evaluation of clinical benefit assessed by RECIST v1.1 determining objective overall response rate (ORR)
Duration of response per RECIST v1.1 as per local Investigator's assessment.
时间窗: 36 Months
To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally
次要结局
- Overall response rate as per Blinded Independent Central Review (BICR)(36 months)
- Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128) assessed locally and BICR(36 months)
- Duration of Response as per BICR(36 months)
- Time to response per RECIST v1.1. as per local investigator assessment(36 months)
- Time to response per RECIST v1.1. as per BICR(36 months)
- Characterize the safety and tolerability of zenocutuzumab (MCLA-128)(6-12 months)
- Maximum plasma concentration [Cmax](36 months)
- Volume of distribution [V](36 months)
- Volume of distribution at steady state [Vss](36 months)
- Area under the concentration versus time curve from time zero to time t [AUC0-t](36 months)
- half-life [t1/2](36 months)
- area under the concentration versus time curve [AUC0-∞](36 months)
- time to reach maximum concentration [tmax](36 months)
- Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)(36 months)
- serum titers of anti-drug antibodies(36 months)
- Evaluation of progression free survival (PFS)(36 months)
- Evaluation of overall survival (OS)(12 months)
研究者
研究点 (62)
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相关资讯
FDA Extends Review of Zenocutuzumab for NRG1+ NSCLC and Pancreatic Cancer- The FDA extended the PDUFA date for zenocutuzumab, a Biologics License Application (BLA) seeking approval for NRG1-positive NSCLC and pancreatic cancer, to February 4, 2025.
- The extension allows the FDA additional time to review chemistry, manufacturing, and controls information related to zenocutuzumab, a HER2 x HER3 bispecific antibody.
- Zenocutuzumab's BLA is supported by phase 1/2 eNRGy trial data, demonstrating promising objective response rates in both NRG1+ NSCLC and pancreatic cancer.
- The FDA previously granted priority review to the BLA in May 2024, highlighting the unmet need for effective therapies in these patient populations.last yearFDA Extends Review of Zenocutuzumab for NRG1 Fusion-Positive Cancers- The FDA has extended the review period for zenocutuzumab, a potential treatment for NRG1 fusion-positive cancers, to February 4, 2025.
- The extension allows the FDA to review additional Chemistry, Manufacturing, and Controls information submitted by Merus N.V., the drug's developer.
- Zenocutuzumab has shown promising objective response rates in clinical trials for non-small cell lung cancer and pancreatic ductal adenocarcinoma.
- The BLA is supported by data from the phase 1/2 eNRGy trial, which demonstrated the agent's safety and antitumor activity.last yearFDA Approves Bizengri for NRG1 Fusion-Positive Lung and Pancreatic Cancers- The FDA has granted accelerated approval to Bizengri (zenocutuzumab-zbco) for advanced pancreatic adenocarcinoma and non-small cell lung cancer with NRG1 gene fusions.
- Bizengri is the first systemic therapy approved by the FDA specifically targeting NRG1 gene fusions in these cancers after prior systemic therapy.
- Clinical trial data showed overall response rates of 40% in pancreatic cancer and 33% in NSCLC, with manageable side effects, supporting the approval.
- This approval highlights the importance of biomarker testing to identify NRG1 fusions, enabling personalized treatment for these difficult-to-treat cancers.last yearFDA Approves Bizengri (zenocutuzumab-zbco) for NRG1+ Pancreatic and Non-Small Cell Lung Cancers• The FDA has granted accelerated approval to Bizengri (zenocutuzumab-zbco) for advanced unresectable or metastatic NRG1+ pancreatic adenocarcinoma and non-small cell lung cancer (NSCLC).
• Bizengri is the first and only FDA-approved therapy specifically targeting NRG1 gene fusions in these cancers, offering a new treatment option for patients with disease progression after prior systemic therapy.
• Approval was based on overall response rate (ORR) and duration of response (DOR) data from the eNRGy trial, with continued approval contingent on confirmatory trial results.
• Bizengri carries a Boxed Warning for Embryo-Fetal Toxicity and warnings for infusion-related reactions, interstitial lung disease/pneumonitis, hypersensitivity/anaphylactic reactions and left ventricular dysfunction.last year