March 2021 saw the return of the ESMO Targeted Anticancer Therapies (TAT) Congress, in a virtual format, after a 2-year hiatus caused by the last-minute cancellation of the 2020 Congress as the COVID-19 pandemic spread rapidly around the globe. However, the virtual format might actually have further increased engagement in this meeting focused on early oncology drug development, given that the number of ‘attendees’ almost tripled, from 380 to 1,127.

Educational sessions covered the breadth of targeted anticancer treatments, from acoustic cluster therapy and antibody–drug conjugates designed to improve the delivery of cytotoxic agents, to a range of molecularly targeted agents, epigenetic drugs and immunotherapies, including engineered T cells, multi-specific T cell engagers, cytokines, oncolytics and microbiota-based interventions. This long list underscores the huge variety and complexity of anticancer strategies that are currently under clinical development. On this background, the 2021 TAT Honorary Award recipient, Ruth Plummer, emphasized the importance of academic–industry partnerships to exploit complementary strengths and overcome weaknesses, thereby improving the adaptability, flexibility and, ultimately, the success of drug development. In his keynote lecture on models for efficient drug development, David Hyman also stressed the importance of approaching this process as a ‘team sport’.

The importance of translational research in prioritizing and refining anticancer strategies was highlighted by a series of talks on preclinical studies to identify combination therapies. In this session, René Bernards presented unpublished data from his group indicating that, akin to their findings with BRAF inhibitors in colorectal cancer, EGFR signalling diminishes the efficacy of the tyrosine kinase inhibitor lenvatinib in hepatocellular carcinoma models. Reportedly, combining this agent with the EGFR inhibitor gefitinib resulted in promising activity in a proof-of-concept clinical study.

In oral abstract sessions, attendees were provided with emerging data on intratumoural immunotherapy with liposomes containing IL-12-encoding mRNA (MEDI1191) in patients previously treated with immune-checkpoint inhibitors, revealing a favourable safety profile and shrinkage of both injected and non-injected lesions, even prior to addition of sequential durvalumab. The novel highly selective PI3Kα inhibitor CYH33 also showed promising single-agent activity, including one complete response, in patients with various PIK3CA-mutated solid tumours — unlike most other PI3K inhibitors. In the phase II ZENITH20 trial, poziotinib resulted in disease control in almost 90% of patients with EGFR or ERBB2 exon 20-mutant non-small-cell lung cancer, who have a particularly poor prognosis. Importantly, the poor tolerability of this agent could be improved with twice-daily versus once-daily dosing, without compromising efficacy.

Once again, the TAT Congress proved to be an engaging meeting covering many exciting new directions in cancer therapy. We look forwards to returning to Paris next year to discuss the trends in phase I oncology in person.