GSK (NYSE:GSK) is pursuing a focused oncology expansion built around hematologic malignancies, gynecologic cancers, lung cancer, gastrointestinal cancers and prostate cancer, with a combination of internal research and business development, according to Hesham Abdullah, the company’s senior vice president and global head of oncology research and development.
Speaking at a Morgan Stanley fireside chat, Abdullah said the company’s return to oncology after stepping away from the field in 2014 has relied on concentrating resources in disease areas where unmet need remains and where GSK can build expertise across research, medical affairs and commercialization.
Business development supports new franchises
Abdullah said GSK evaluates potential licensing transactions and acquisitions against several criteria: whether they address a distinct unmet need, offer differentiated drug design or mechanism, have supportive preliminary clinical data, and fit strategic disease areas where GSK has established capabilities.
He described GSK’s acquisition of Nuvalent as more than a single-asset transaction. The deal includes neladalkib, a fourth-generation ALK inhibitor, and zidesamtinib, marketed as Jideytro, for ROS1-positive patients, as well as a discovery pipeline.
Jideytro was approved in July, Abdullah said. GSK plans to file for its use in first-line, TKI-naive ROS1-positive non-small cell lung cancer patients during the fourth quarter. Data presented at a scientific meeting included 94 patients and showed a 94% objective response rate, a progression-free survival landmark of about 90% at 12 months, and an 86% duration-of-response landmark at 12 months, according to Abdullah.
Among patients with brain metastases in that study, Abdullah said the intracranial response rate was 100%. He noted that brain metastases can develop in roughly 30% to 50% of patients with ROS1- or ALK-positive disease.
For neladalkib, GSK is conducting the ALKAZAR Phase III trial in first-line ALK-positive lung cancer against alectinib. Abdullah said alectinib remains a relevant control arm, citing physician usage estimates of about 45% for alectinib and 35% for lorlatinib in the frontline setting. He said trial recruitment had reached 47%, up from roughly 35% cited several weeks earlier.
Abdullah said liver enzyme elevations observed with neladalkib have generally been asymptomatic, transient and reversible, often within about two weeks.
B7-H3 program advances in lung and prostate cancer
GSK is advancing its B7-H3 antibody-drug conjugate, referred to as Ris-Rez, across small cell lung cancer and prostate cancer. Abdullah highlighted Phase III data from partner Hansoh Pharma in second-line small cell lung cancer comparing Ris-Rez with topotecan.
- Overall survival hazard ratio of 0.46
- Progression-free survival hazard ratio of 0.33
- Median overall survival of about 18.5 months for Ris-Rez
- Nearly fivefold improvement in objective response rate, according to Abdullah
The study was conducted in China, but Abdullah said GSK has seen consistency between Hansoh’s findings and data from GSK’s own global development program. He also pointed to the topotecan control arm’s median overall survival of approximately 10.3 months, which he said was comparable with a 10.6-month result for the topotecan arm in another global Phase III study.
GSK has enrolled and treated its 1,000th patient in the global Ris-Rez development program, Abdullah said. The company is initiating five Phase III studies, including an ongoing second-line small cell lung cancer study, a planned first-line small cell lung cancer study, and three studies in prostate cancer.
In metastatic castration-resistant prostate cancer, Hansoh data showed a 37% confirmed objective response rate, Abdullah said, adding that the response rate appeared consistent regardless of prior chemotherapy exposure.
Other pipeline priorities
GSK is also developing its B7-H4 antibody-drug conjugate, Mo-Rez, in gynecologic cancers. Abdullah cited preliminary data showing a 67% confirmed objective response rate at a 5.8 mg/kg dose in platinum-resistant ovarian cancer and a 67% objective response rate at a 4.8 mg/kg dose in second-line endometrial cancer.
He said GSK is examining multivariate biomarkers beyond antigen expression to potentially improve patient selection and treatment benefit. In a preliminary B7-H4 dataset presented at the Society of Gynecologic Oncology meeting, the incidence of interstitial lung disease was 3%, with most events low grade, he said.
Abdullah identified Ris-Rez, Mo-Rez, velzatinib in gastrointestinal stromal tumors, the Nuvalent assets and Blenrep in multiple myeloma as important contributors to GSK’s longer-term oncology ambitions. He said the company expects to have five approved oncology medicines currently, a sixth by year-end, and potentially three additional products by 2029.
Looking ahead, Abdullah said GSK remains interested in differentiated opportunities in areas including RAS-targeted therapies, antibody-drug conjugates and driver mutation-defined cancers, while maintaining discipline over areas it chooses not to pursue.
About GSK (NYSE:GSK)
GSK plc is a global biopharmaceutical company headquartered in Brentford, England. The company researches, develops and manufactures medicines and vaccines for the prevention and treatment of disease, serving patients and healthcare providers in markets around the world.
GSK focuses on specialty medicines and vaccines in areas including infectious diseases, HIV, respiratory disease, immunology and oncology. Its products include prescription medicines, long-acting treatments and vaccines designed to protect against diseases such as shingles, meningitis, influenza and respiratory syncytial virus (RSV).
The company was formed in 2000 through the merger of Glaxo Wellcome and SmithKline Beecham.
