Intas Pharma Told to Narrow Margins, Extend Duration in Pembrolizumab Trial Protocol
New Delhi: The Subject Expert Committee (SEC) under the Central Drugs Standard Control Organisation (CDSCO) has directed Intas Pharmaceuticals Ltd. to revise its clinical trial protocol for a proposed Phase I/III study of its pembrolizumab biosimilar candidate INTP58.
The firm had presented its proposal for grant of permission to conduct “A Phase-1/3, Randomized, Assessor-Blind, Active Controlled, Parallel, Two Arm, Multicenter Study, to Compare Efficacy, Safety, Pharmacokinetics, and Immunogenicity of INTP58 versus Keytruda, Both Administered With Platinum-Doublet Chemotherapy, in the First-Line Treatment of Patients With Locally Advanced or Metastatic Squamous or Non-Squamous Non-Small Cell Lung Cancer” (Protocol No. 0142-25, Version 1.0, dated April 22, 2025).
After detailed deliberation, the SEC did not grant immediate approval but recommended five major modifications to the study protocol before further evaluation. The SEC recommended several modifications namely, the inclusion of adequately powered PFS and OS as primary endpoints, narrowing of the inferiority margin, reduction in paclitaxel dosage, extension of study duration with OS assessment at 52 weeks, and subgroup analysis as per PD-L1 expression levels.
Pembrolizumab, marketed globally by MSD as Keytruda, is a PD-1 inhibitor widely used in the treatment of various cancers, including NSCLC. INTP58 represents Intas’ proposed biosimilar of pembrolizumab, being developed for use in combination with platinum-doublet chemotherapy in patients with advanced squamous and non-squamous NSCLC.
The SEC highlighted that Progression-Free Survival (PFS) and Overall Survival (OS) are critical efficacy measures in NSCLC trials and should be adequately powered and included as primary endpoints. To ensure meaningful comparison, the committee advised narrowing of the inferiority margin, which would establish non-inferiority of INTP58 to Keytruda more convincingly.
Further, the dose of paclitaxel proposed in the trial was advised to be reduced, in line with standard clinical practice, to minimize potential adverse effects. The committee also emphasized the need to extend the duration of the study, with Overall Survival being assessed at around 52 weeks, to ensure long-term efficacy and safety data are captured.
Importantly, the SEC recommended conducting subgroup analyses based on PD-L1 expression, considering that PD-L1 levels play a significant role in predicting responses to PD-1 inhibitors in NSCLC patients.
In conclusion, the SEC directed Intas Pharmaceuticals to submit a revised protocol incorporating all the above modifications for further evaluation. The committee stressed that these adjustments are essential for generating robust, reliable clinical evidence that would not only support potential regulatory approval of INTP58 but also guide its place in clinical practice for the management of NSCLC.
