Results of the Phase 2 afatinib clinical trial supported by the Chordoma Foundation were recently presented at the annual meeting of the American Society of Clinical Oncology (ASCO), the world’s largest oncology conference.
The investigators report that out of 30 patients for which afatinib was a first-line systemic therapy, 40% avoided tumor progression at 12 months, and 4 (13%) achieved a partial response by RECIST criteria (meaning the tumor shrank by at least 30%). Remarkably, the median progression-free survival for patients with a partial response was nearly 28 months. In a second cohort, for which afatinib was given after patients had already progressed on other therapies, 38.5% were progression free at 9 months. In both the first and later line cohorts, the predefined criteria of success of 30% progression free survival at 12 or 9 months, respectively, was exceeded.
These results demonstrate that a subset of chordoma patients benefit from afatinib for a sustained period. They also create an urgent need to identify biomarkers that can predict which patients are most likely to benefit from EGFR inhibitors like afatinib, and which patients are unlikely to benefit and therefore can avoid the potential side effects and opportunity cost of trying EGFR inhibitors. Follow-on research to identify such biomarkers is currently being pursued by the study investigators, by Chordoma Foundation Labs (CF Labs), and by others.
We’re deeply grateful to the investigators at Leiden University Medical Center, Istituto Nazionale dei Tumori, and University College London, and to the patients and donors who made this important trial possible, helping to uncover a new treatment option.
Other chordoma-related highlights from ASCO included:
Phase 2 trial testing ERAS-601 +/- cetuximab (SHP2 inhibitor +/- EGFR inhibitor): A detailed summary is available here, but briefly, the trial — which builds on results of our partnership with the Schreiber Lab at the Broad Institute of MIT and Harvard and work from CF Labs — yielded promising results, with the majority of chordoma patients experiencing some tumor shrinkage.
Phase 1 trial of tuvusertib + avelumab (ATR Inhibitor + immune checkpoint inhibitor): The only partial response observed in this trial was in a chordoma patient, reinforcing our ongoing interest in ATR as a target in chordoma.
Phase 1 trial of KB-0742 (CDK9 inhibitor): This study showed interesting signs of activity in transcriptionally addicted cancers like chordoma, with 5 chordoma patients included based on preclinical activity.
Signal-finding study of nivolumab + relatlimab (immune checkpoint inhibitors): Results showed a partial response in 1 of 9 chordoma patients and stable disease in 4 patients at 1 year, consistent with previous results with immune checkpoint inhibitors.
Patients and caregivers with questions about clinical trial participation are encouraged to reach out to our Patient Navigators. A full list of clinical trials testing drugs endorsed by our Medical Advisory Board is available here. In particular, we’re continuing to encourage patients with advanced chordoma to speak with their doctors about whether the cetuximab clinical trial we’re supporting at MD Anderson Cancer Center may be appropriate for them. Financial assistance for trial-related travel costs is available.