ESMO Introduces New Framework for Evaluating Tumor-Agnostic Potential of Cancer Treatments

To address the need for standardized tumor-agnostic drug development, the ESMO Precision Medicine Working Group (PMWG) has teamed up with global experts. They created the ESMO Tumor-Agnostic Classifier and Screener (ETAC-S). This tool provides clear minimum requirements for assessing and claiming the tumor-agnostic potential of molecularly guided treatment options (MGTOs). Consequently, it simplifies the screening process for these treatments.

ESMO ETAC-S Standardizes Tumor-Agnostic Drug Validation, Expanding Treatment Options and Streamlining Approval

The recent development in cancer drug research addresses a critical gap by shifting focus from organ-specific treatments to therapies targeting broader biomarker profiles. Traditionally, treatments focused on specific cancer types. However, there is now a significant shift towards therapies that target a wider range of diseases based on molecular biomarkers. Defining and validating a drug’s tumor-agnostic potential has become essential, as it broadens treatment options and enhances patient outcomes. The ESMO ETAC-S framework provides standardized guidelines for assessing and classifying these therapies, helping researchers, pharmaceutical companies, and regulators streamline the development and approval process. This standardization supports the advancement of personalized medicine and expands treatment options for a wider patient population.

Dr. Benedikt Westphalen, Chair of the ESMO PMWG, discussed the ongoing shift from organ-specific to biomarker-driven therapies that target a broad spectrum of diseases. “Over the last couple of years, we have seen a shift in the development of molecularly guided treatment options, away from organ-based development and towards biomarker-driven therapies that have activity across a broad spectrum of diseases,” said Dr. Westphalen. He pointed out that, until recently, the criteria for defining tumor-agnostic drugs were unclear. “ETAC-S aims to bridge this gap by providing a standardized set of minimum requirements and a classification system, designed to be integrated into the various steps of the drug development process,” he continued. The ETAC-S framework helps investigators, pharmaceutical companies, and regulators evaluate the tumor-agnostic potential of MGTOs, guiding subsequent development steps.

ETAC-S Framework Evaluates 3 Key Criteria for Tumor-Agnostic Potential in Early Phase Cancer Trials

The ETAC-S framework is used at the end of early phase trials to evaluate new therapies for tumor-agnostic potential. Dr. Diogo Martins-Branco, co-first author of the manuscript, explained that the therapy must show an objective response in at least 20% of patients in two-thirds of the studied tumor types. Additionally, the therapy must demonstrate efficacy in at least four different tumor types, with five evaluable patients per type, particularly in refractory disease. This screening helps determine whether the MGTO can generate confirmatory evidence across various tumor types or should be studied further within a specific cancer type. This process plays a key role in guiding drug development by validating therapies for broader use or refining their application. Tumor-agnostic potential refers to the ability of a therapy to be effective across multiple cancer types, targeting specific genetic mutations or molecular alterations rather than a single organ or tissue.

Methodology Behind ETAC-S Framework Validated Through FDA-Approved Tumor-Agnostic Therapies

Westphalen, Martins-Branco, and their team detailed the methodology for setting tumor-agnostic criteria in a recent Annals of Oncology publication. They reviewed data from seven tumor-agnostic indications approved by the FDA and EMA as of December 2023. By analyzing key factors such as ORR, tumor types studied, and patient numbers per type, they established minimum requirements for tumor-agnostic potential. They then validated these criteria using data from two 2024 FDA approvals: trastuzumab deruxtecan for HER2-positive solid tumors and repotrectinib for tumors with NTRK gene fusion. Additionally, the team introduced a conceptual taxonomy to categorize therapies as tumor-agnostic, tumor-modulated, or tumor-restricted based on their interaction with tumor biology. This taxonomy offers a more refined approach to understanding how therapies target molecular aberrations across different cancer types.

Martins-Branco highlighted the potential impact of categorizing therapies by molecular and tumor-specific effects. The group plans to refine ETAC-S by distinguishing tumor-agnostic from tumor-modulated therapies. Westphalen noted that ETAC-S will shift cancer classification toward molecular alterations, accelerating drug development and improving access to effective therapies.

Author

Bernice Lottering