Zydus Lifscience Gets CDSCO Panel Nod To study Anti-cancer Drug Pertuzumab

New Delhi: Zydus Lifsciences has got approval from the Subject Expert Committee SEC functional under the Central Drug Standard Control Organisation (CDSCO) for a phase IV study to evaluate the safety of Pertuzumab (Sigrima, Zydus Lifesciences Limited) in patients with HER2-positive metastatic and early breast cancer.

This came after Zydus Lifsciences presented the proposal to conduct the Phase IV study titled “A Phase 4, Prospective, Multicenter, Single- Arm Study to Evaluate the Safety of Pertuzumab (Sigrima™, Zydus Lifesciences Limited) in Patients with HER2-Positive Metastatic and Early breast Cancer.” vide Protocol No: PERT.24.001 Version 01 dated 03.10.2024.

Pertuzumab is an antineoplastic agent used in the treatment of HER2-positive metastatic breast cancer in combination with other antineoplastic agents. Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). It consists of two heavy chains and two lights chains that have 448 and 214 residues respectively.

Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase receptor that plays an integral role in cell proliferation, differentiation, and survival. HER2 becomes active following dimerization with another HER2 receptor, another member of the HER protein family (e.g. HER3), or with a ligand - this dimer then phosphorylates and activates numerous intracellular signaling proteins, initiating signal transduction via pathways that include the Ras/mitogen-activated protein kinase pathway, the phosphatidylinositol 3' kinase (PI3K)/Akt pathway, and then Janus kinases/signal transducer and activator transcription pathway. HER2 is also a known oncogene - it is overexpressed or gene-amplified (i.e. HER2-positive) in approximately 20% of breast cancers and these cancers carry a generally poorer prognosis than HER2-negative breast cancers.

Pertuzumab targets the extracellular dimerization domain (subdomain II) of HER2, thereby inhibiting ligand-initiated intracellular signaling via the MAP kinase and PI3K pathways. Inhibition of these pathways results in inhibition of cell growth and the initiation of apoptosis, respectively. Pertuzumab also appears to mediate antibody-dependent cell-mediated cytotoxicity.

At the recent SEC meeting for Oncology held on 5th December 2024, the expert panel reviewed the proposal to conduct the Phase IV study titled “A Phase 4, Prospective, Multicenter, Single- Arm Study to Evaluate the Safety of Pertuzumab (Sigrima, Zydus Lifesciences Limited) in Patients with HER2-Positive Metastatic and Early Breast Cancer.”

After detailed deliberation, the committee recommended the approval to conduct the Phase IV study with following changes in the protocol

1. The number of cycles to be increased for the patients who are responding to the treatment of 6 cycles in adjuvant and metastatic cancer settings at least for one year.

2. The sample size should be increased considering the different settings of treatment for metastatic and early breast cancer, and the number of patients in each cancer setting should be proportionate.

3. PI should be medical oncologist.

In line with the above, the expert panel stated that the firm should submit revised protocol to CDSCO for further evaluation

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