Zydus' Pembrolizumab Trial: CDSCO Panel Seeks Protocol Changes
New Delhi: The Subject Expert Committee (SEC) under the Central Drugs Standard Control Organisation (CDSCO) has recommended four modifications to Zydus Life Sciences Limited's proposed Phase I/III clinical trial protocol for biosimilar pembrolizumab.
The recommendations include narrowing the non-inferiority margin and following participants for at least one year after completion of the planned treatment cycles. The committee also recommended conducting immunogenicity assessments at the end of the study and excluding day-care sites from the proposed trial sites. The company has been asked to incorporate these changes and submit the revised protocol for further deliberation.
The recommendations were made during the SEC (Oncology) meeting held on October 28, 2026, following the company’s presentation of its proposal for Pembrolizumab solution for intravenous infusion, 100 mg/4 mL (25 mg/mL).
The firm presented the proposal to conduct “A Phase I/III, Multi-center, Randomized, Double-Blind, Active-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Immunogenicity of Biosimilar Pembrolizumab (ZRC-3323) Compared with Reference Pembrolizumab (Keytruda®), Administered in Combination with Pemetrexed and Carboplatin as First-Line Treatment in Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer without EGFR Sensitizing Mutations or ALK Genomic Tumor Aberrations” vide Study/Protocol No.: PEMB.26.001 Version Number: 01 dated 24.08.2026”
The proposed study aims to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of the biosimilar compared with the reference product, with both administered in combination with pemetrexed and carboplatin. The combination is proposed as first-line treatment in patients with metastatic non-squamous non-small cell lung cancer without EGFR sensitising mutations or ALK genomic tumour aberrations.
Pembrolizumab is a PD-1 blocking antibody used to treat various types of cancer, including metastatic melanoma, non small-cell lung cancer, cervical cancer, head and neck cancer, and Hodgkin's lymphoma. Pembrolizumab is a highly selective IgG4-kappa humanized monoclonal antibody against PD-1 receptors.
Pembrolizumab binds with high affinity to the cell surface receptor programmed cell death protein 1 (PD-1) and antagonizes its interaction with its known ligands PD-L1 and PD-L2. Under normal circumstances, the binding of the ligands of PD-1 to the receptor inhibits the TCR-mediated T-cell proliferation and cytokine production. This inhibitory signal appears to play a role in self-tolerance and collateral damage minimization after immune responses against a pathogen and maternal tolerance to fetal tissue.
The binding of pembrolizumab to PD-1 prevents this inhibitory pathway, causing a physiological shift towards immune reactivity and enhancing tumor immunosurveillance and anti-tumor immune response.
After detailed deliberation, the committee recommended the following modifications to the proposed clinical trial protocol:
1. The non-inferiority margin used for sample size calculation should be narrowed and sample size calculation should be done accordingly.
2. The protocol should include follow-up of trial participants for at least one year after completion of the planned treatment cycles.
3. Immunogenicity assessments should be conducted at the end of the study to adequately evaluate the immunogenicity profile of the drug product.
4. Day-care sites should be excluded from the list of proposed clinical trial sites.
Accordingly, Zydus Life Sciences Limited has been asked to incorporate these recommendations and submit the revised clinical trial protocol for further deliberation before the committee.
