India's drug regulatory authority has granted conditional approval to Pfizer for conducting Phase 3 clinical trials of Disitamab Vedotin, a novel antibody-drug conjugate (ADC) targeting HER2-positive solid tumors.
The Subject Expert Committee (SEC) for Oncology, functioning under the Central Drug Standard Control Organization (CDSCO), reviewed Pfizer's Phase 3 clinical study protocol (C5731001 amendment 03) during its meeting on March 11, 2025. After detailed deliberation, the committee recommended permission for the trial with specific conditions.
Conditional Approval Requirements
The regulatory approval comes with two key stipulations:
- Pfizer must include more geographically distributed government sites across India in the study
- The principal investigators must be medical oncologists only
These conditions aim to ensure broader representation in the trial population and appropriate specialist oversight for this advanced oncology therapy.
Mechanism of Action and Therapeutic Potential
Disitamab Vedotin, also known as RC48, represents an innovative approach to targeted cancer therapy. As an antibody-drug conjugate, it combines:
- A monoclonal antibody specifically targeting human epidermal growth factor receptor 2 (HER2)
- The cytotoxic agent monomethyl auristatin E (MMAE)
The mechanism involves the antibody binding to HER2 receptors on cancer cells, followed by internalization of the complex. Once inside the cell, the cytotoxic MMAE is released, inhibiting tubulin polymerization and ultimately leading to cell death. This approach may also produce a bystander killing effect on neighboring cancer cells.
The drug has shown particular promise for treating HER2-positive gastric cancer and urothelial cancer, addressing significant unmet needs in these difficult-to-treat malignancies.
Strategic Importance for Pfizer
This approval marks an important step in Pfizer's oncology portfolio expansion in India. ADCs represent one of the fastest-growing segments in cancer therapeutics, combining the targeting precision of monoclonal antibodies with the cell-killing power of cytotoxic agents.
The Phase 3 trial will help establish Disitamab Vedotin's efficacy and safety profile in Indian patients, potentially leading to a new treatment option for patients with HER2-positive solid tumors who currently have limited therapeutic options.
Regulatory Context
The CDSCO's conditional approval reflects the regulatory body's commitment to advancing innovative cancer therapies while ensuring appropriate trial design and patient safety. The requirement for geographically distributed sites will help ensure that the trial results represent India's diverse population.
As the trial progresses, oncologists and patients will be watching closely to see if Disitamab Vedotin can deliver on its promise of targeted efficacy with manageable toxicity in treating HER2-positive cancers.
