Phase I trial of gemcitabine plus trastuzumab and pertuzumab in previously treated metastatic HER2+ breast cancer.

595Background: In HER2+ breast cancers, HER2 forms heterodimers with HER3 to activate its signaling cascade. Dual HER2 blockade with trastuzumab (T) + pertuzumab (P) prevents heterodimerization and is superior to trastuzumab alone. Prior trials suggest a role for continued T beyond progression, so a study was proposed to assess the role of T+P in the salvage setting. A phase 1/2 trial is ongoing to assess the safety and efficacy of gemcitabine (G) + TP in metastatic HER2+ pretreated patients. (NCT02139358) Here we report the data for the completed phase 1 cohort. Methods: The phase 1 trial used a 3+3 design with 3 dose levels (DL), starting at DL0. DL0 used G 1200mg/m2 IV D1, 8 + T 6 mg/kg IV D1, P 420mg IV D1 q21 days (after loading doses on C1D1). DL-1 is identical to DL0 but used G at 1000mg/m2 and DL -2 used G at 850mg/m2. Primary endpoint(s) were recommended phase 2 dose (RP2D) and safety/toxicity. DLT definition was any 1stcycle unexpected ≥ G3 non-hematologic or ≥ G4 hematologic toxicity leading to...