Targeted therapy for advanced solid tumors based on molecular profiles: Early results from MyPathway, an open-label, phase IIa umbrella basket study

LBA11511 Background: The MyPathway study (NCT02091141) evaluates agents targeting the HER2, BRAF, Hedgehog (Hh), or EGFR pathways in non-indicated tumors with relevant genetic abnormalities. Early results from MyPathway merit pre-planned tumor-cohort expansion. Methods: Eligible pts had advanced solid tumors with no curative therapy and molecular alterations in HER2, BRAF, Hh, or EGFR. Pts received standard doses of trastuzumab + pertuzumab (for the HER2 pathway), vemurafenib (BRAF), vismodegib (Hh), or erlotinib (EGFR) based on alteration. The primary endpoint is investigator-evaluated response rate within a tumor-pathway cohort (RECIST 1.1). Cohort size and expansion is determined by Simon’s two-stage design criteria. Results: By December 14, 2015, MyPathway included 129 pts with available baseline assessments and alterations in HER2 (n = 82; 53 amplifications, 23 mutations, 5 both, 1 RBMS-NRG1 fusion), BRAF (n = 33; 18 V600E, 15 other), Hh (n = 8; 7 PTCH1, 1 SMO), or EGFR (n = 6). Pts had a median of 3 (range, 0–10) prior lines of therapy. Best responses (n = 118) are shown below; 11 pts had insufficient follow-up for reevaluation and were not analyzed. 22 pts had PR/CR (1 CR); current response durations were up to 11 months. Conclusions: Targeted therapy produced responses in pts with 9 different tumor types outside of current drug indications. As enrollment increases for all tumor-pathway cohorts, analyses of tumor responses based on specific alterations (eg, HER2 amplifications vs. mutations) are planned. The HER2 amplified colorectal, bladder, and biliary, and the BRAF lung cohorts will be expanded based on observed activity. Clinical trial information: NCT02091141. [Table: see text]