CDSCO Committee Seeks Efficacy-Focused Redesign of Intas' Pembrolizumab Clinical Trial
New Delhi: The Subject Expert Committee (SEC) under the Central Drugs Standard Control Organisation (CDSCO) has advised Intas Pharmaceuticals to revise and resubmit its proposed Phase I/III clinical trial protocol for Pembrolizumab Concentrate for Solution for Infusion 100 mg /4 mL Vial (25 mg/mL).
This came after the firm presented a proposal to conduct a Phase I/III clinical trial titled "A Randomized, Double-Blind, Active-Controlled, Parallel, Three-Arm, Multicenter Study Comparing Pharmacokinetics, Efficacy, Safety and Immunogenicity of INTP58 and Keytruda, both Administered in Combination with Platinum – Pemetrexed Chemotherapy for the First-Line Treatment in Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer vide Protocol No.: 0265-24, Version No.: 1.0, Dated 20-Jun2025 meant for USFDA and EMA submission only."
At the SEC (Oncology) meeting held on 16 October 2025, the expert panel reviewed the proposal and advised that the protocol required significant strengthening. The committee recommended that efficacy should be included as one of the primary endpoints of the study. It further directed that a non-inferiority margin of 10–12% be applied to ensure the statistical robustness of the trial. In line with these modifications, the panel also instructed the firm to recalculate the sample size to adequately power the study.
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 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 changes in the protocol:
1. Efficacy parameters should be one of the primary endpoints of the study.
2. Non-inferiority margin should be of 10-12 % for the robustness of the study.
3. Sample size should be recalculated accordingly.
Accordingly, the expert panel suggested that the firm should submit revised protocol to CDSCO for further evaluation by the committee.
