July 7, 2022

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The dual antibody Zenocutuzumab obtained FDA fast track qualification

The dual antibody Zenocutuzumab obtained FDA fast track qualification

The dual antibody Zenocutuzumab obtained FDA fast track qualification. It is used to treat patients with metastatic solid tumors (NRG1+cancers) carrying NRG1 gene fusion who have progressed after receiving standard therapies.

On January 7, 2021, Merus NV announced that the FDA has granted Zenocutuzumab (Zeno) fast-track qualification for the treatment of patients with metastatic solid tumors (NRG1+ cancers) carrying NRG1 gene fusion who have progressed after receiving standard treatments.

 

In July last year, the FDA also granted zenocutuzumab orphan drug designation for the treatment of pancreatic cancer.

NRG1 (Neuroregulin1, neuregulin 1) gene fusion is a rare set of genomic mutations that appear as a driving factor for tumorigenesis and growth in many types of solid tumors, including lung cancer, breast cancer, pancreatic cancer, ovarian cancer, and tumor Rectal cancer. However, the frequency of NRG1 gene fusion is low, occurring in about 3% of non-small cell lung cancer patients, 0.5-1.5% of pancreatic cancer patients, and less than 1% in other cancers.

Merus is committed to applying its Multiclonics technology platform to develop innovative fully human bispecific and trispecific antibody therapies, including bi-antibody platform Biclonics and tri-specific antibody platform Triclonics. Pre-clinical and clinical studies have shown that antibodies obtained using Multiclonics technology have the advantages of long half-life, low risk of immunogenicity, enhanced ADCC and Fc silencing. The EGFR/cMET double anti-MCLA-129 introduced by Betta Pharmaceuticals from Merus was built on the Biclonics platform.

 The dual antibody Zenocutuzumab obtained FDA fast track qualification  

Zenocutuzumab (MCLA-128; PB-4188) is an ADCC-enhanced IgG antibody developed using Merus’ Biclonics technology and MeMo technology to target HER-2 and HER-3. Its DOCK & BLOCK® mechanism of action is particularly suitable for targeting NRG1+ cancer.

The dual antibody Zenocutuzumab obtained FDA fast track qualification

Since the activation of the neuregulin signaling pathway requires the combination of HER2 and HER3 to form a heterodimer, zenocutuzumab can block neuregulin signaling by preventing the formation of heterodimers.

The dual antibody Zenocutuzumab obtained FDA fast track qualification

Merus initiated the Phase I/II clinical trial eNRGy in January 2015 to evaluate the safety and effectiveness of zenocutuzumab as a single agent for NRG1+ cancer patients. The study was divided into 3 cohorts, including non-small cell lung cancer, pancreatic cancer and other solid tumors.

Research data published in October 2019 showed that zenocutuzumab reduced the size of tumors in many patients. After receiving treatment for more than 7 months, a patient with pancreatic cancer reduced the tumor diameter by 54%, achieving partial remission; another patient with pancreatic cancer reduced the tumor diameter by 25%, achieving stable disease; and another patient with NSCLC was receiving treatment for 5 months The tumor diameter decreased by 41%.

In terms of safety, at the recommended dose (750mg, iv, q1w-q3w), the most common adverse events (AE) were grade 1-2, and <5% of patients were grade 3, and there were no grade 4 AEs. In July 2020, Merus announced a collaboration with Caris Life Sciences, Foundation Medicine, and Tempus Labs to find NRG1+ cancer patients who may participate in the trial.

The dual antibody Zenocutuzumab obtained FDA fast track qualification

In January 2018, Merus launched a phase II clinical trial (NCT03321981) to evaluate zenocutuzumab combined with trastuzumab, combined with trastuzumab + chemotherapy, or combined with hormone therapy (fulvestrant) for the treatment of metastases For breast cancer patients, cohort 1 is HER2 positive/amplified, cohort 2 is ER positive/HER2 low expression.

The primary endpoint is the clinical benefit rate (CBR) at 24 weeks. Data released in May 2020 showed that the 24-week CBR was 35.1%, ORR was 18.9%, 2.7% of patients achieved CR, 16.2% of patients achieved PR, SD was observed in 59.5% of patients, and 21.6% of patients occurred. Disease progression. The most common grade 3-4 treatment-related adverse events were diarrhea (4%) and neutropenia (46%, both related to vinorelbine).

 

(sourcechinanet, reference only)


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