GSKs Lung Cancer ADC Earns FDA Breakthrough Designation

The FDA has granted breakthrough status to an antibody-drug conjugate (ADC) that GSK licensed from China’s Hansoh Pharma in a $1.7 billion agreement last year.

The pharma firm said that GSK5764227 (GSK’227, formerly known as HS-20093) has been granted the coveted designation for the use of the ADC to treat relapsed or refractory extensive-stage small-cell lung carcinoma (SCLC). This designation is the result of encouraging early clinical results in this tumor type.

Immunoregulatory protein B7-H3, sometimes referred to as CD276; it is overexpressed in tumor tissue, particularly in lung, breast, ovarian, stomach, and brain cancers as well as skin squamous cell carcinomas. Because of its low expression in healthy tissues, it presents an intriguing target for treatment that could prevent unintended side effects.

According to Hesham Abdullah, global head of oncology, R&D at GSK, extensive-stage small-cell lung cancer is aggressive, has a poor prognosis, and represents a huge need for innovative therapies.

Phase 1 results, published at the ASCO meeting last year, showed indications of disease control in 34 out of 40 (85%) strongly pretreated patients with sarcoma, non-small cell lung cancer (NSCLC), and SCLC, with 14 partial responses. In the SCLC subgroup, where seven out of nine patients exhibited tumor decrease, the findings were very impressive.

In this case, patients have usually witnessed a development of their cancer during or after chemotherapy, and they have extremely limited alternatives for treatment.

About 15% of all lung cancers in the US are SCLCs, and 70% of these patients have extensive-stage illness, which indicates that the cancer has progressed to other regions of the body in addition to one or both lungs. The five-year survival rate is a pitiful 3% when it reaches that stage.

As part of our wider ADC initiative, which focuses on discovering novel therapy alternatives with transformative and first-to-market potential, Abdullah said, Breakthrough status supports our ambition to accelerate GSK’227 for these patients.

For the rights to GSK’227 outside of China, Hong Kong, Macao, and Taiwan, GSK paid $185 million up front in December of last year. A further $1.525 billion was paid at success-based milestones.

It is attempting to catch up to ifinatamab deruxtecan (I-DXd), another B7-H3 ADC candidate from Daiichi Sankyo and MSD, which began a phase 3 study in extensive-stage SCLC earlier this month. Vobramitamab duocarmazine, or vobra duo, is an ADC developed by MacroGenics that is now undergoing phase 1 and phase 2 trials for colorectal cancer and other solid tumors.

After securing rights to HS-20089, a B7-H4 targeted ADC with promise as a triple-negative breast cancer therapy, for $85 million upfront and potentially to $1.5 billion in milestones, the business obtained GSK’277, its second licensed ADC from Hansoh. The cell-killing payload of both ADCs is a patented topoisomerase inhibitor created by Hansoh.