Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2-positive breast cancer.

TPS666 Background: Integrated analysis of whole genome RNAi screening with computationally reverse engineered interactome models identified IL6/JAK/STAT as a master regulator pathway essential for growth of ErbB2/HER2 positive breast cancer. Ruxolitinib (R), FDA-approved treatment for myelofibrosis, inhibits JAK1 and JAK2. The combination of R plus Trastuzumab (T) is synergistic in tumor growth inhibition in mouse xenografts of HER2 amplified breast cancer cell lines. These data provide a strong rationale for studying the efficacy of combination R and T in a clinical trial. Methods: A multi-center, open-label, phase I/II (P1/2) trial of R plus T in HER2+ metastatic breast cancer (MBC) who have progressed on T-based therapy. P1 will be an adaptive design with 10 patients, using the time-to-event continual reassessment method. The recommended P2 dose (RP2D) will be used in a non-randomized, open-label P2 trial with 30 evaluable patients. Given the anticipated limited overlapping toxicities, 33 patients are ...