MyPathway

MyPathway opened in April 2014 as an open-label, multi-basket phase 2 run by Genentech at community and academic sites in the United States. Patients whose tumours carried a HER2 alteration, an EGFR mutation, a BRAF mutation, a Hedgehog pathway alteration, an ALK rearrangement or, later, high tumour mutational burden or microsatellite instability received the matching approved drug outside its licensed indication, with objective response as the endpoint in each drug-by-tumour cohort. It enrolled 673 patients before completing.

The first report, by John Hainsworth and colleagues in the Journal of Clinical Oncology in 2018, covered 230 treated patients and found responses in 23 percent overall, with the strongest signals for trastuzumab plus pertuzumab in HER2-amplified colorectal cancer and for vemurafenib in BRAF V600-mutant non-melanoma cancers. The updated colorectal cohort, in the Lancet Oncology in 2019, reported a response rate of 32 percent in 57 patients with HER2-amplified, treatment-refractory disease, most durable in RAS wild-type tumours; that result put trastuzumab plus pertuzumab into United States guidelines for HER2-amplified colorectal cancer. The atezolizumab cohort, in Cancer Discovery in 2022, showed that response to single-agent PD-L1 blockade in unselected tumours rose with tumour mutational burden and was concentrated in the most highly mutated tumours.

MyPathway is the industry counterpart to NCI-MATCH and TAPUR, and the model for Roche's later TAPISTRY platform. It showed a company could generate label-adjacent evidence cheaply from a basket, and it produced two of the more reliable tumour-agnostic signals (HER2 amplification for dual HER2 blockade and BRAF V600 for BRAF inhibition) alongside many cohorts with little activity.