Tumor-Agnostic Therapies: Trials on Biomarkers and Precision Cancer Care

Vivek Subbiah, MD, chief of early-phase drug development at Sarah Cannon Research Institute (SCRI), highlighted the growing importance of tumor-agnostic cancer therapies at the European Society for Medical Oncology (ESMO) conference. This approach to treatment moves beyond traditional anatomical classifications (eg, breast, lung, or prostate cancer) to focus on genetic biomarkers that drive the disease, arguing that if a biomarker-targeted therapy works in 1 tumor type, it's likely to work in others.

Subbiah notes that this concept, which began with the FDA’s first tumor-agnostic approval in 2017 for pembrolizumab (Keytruda) in cancers with microsatellite-instability–high or mismatch-repair–deficient solid tumors, is now poised for rapid expansion.

At ESMO, he presented 2 key clinical trials illustrating different facets of this strategy:

• DiscovHER PAN-206 Trial (Zanidatamab): This phase 2 trial explores new applications for an already approved drug, zanidatamab, a dual HER2-targeted bispecific antibody. It is being tested in 3 cohorts of patients with previously treated HER2-positive/IHC3-positive solid tumors, including those with breast cancer who have progressed after receiving the standard HER2-targeted therapy, trastuzumab deruxtecan (Enhertu). The goal is to find better-tolerated options for patients.
• GUARDIAN-101 Trial (CLSP-1025): This is a first-in-human trial involving a novel therapy, CLSP-1025, which uses diabody technology to create a T-cell engager. This therapy is designed to target the common, previously considered "undruggable," p53 R175H mutation across various solid tumors. By selectively binding the mutated p53 and a T-cell protein (CD3), it aims for potent and specific tumor killing.

Ultimately, Subbiah champions the tumor-agnostic approach to eliminate "molecular inequity." He believes developing drugs based on biomarkers across multiple tumor types is crucial to ensuring that patients with rare cancers also have equitable access to lifesaving precision medicine. Better biomarkers and artificial intelligence are accelerating this shift, making trials faster and more cost-effective.