A Phase I Study Of Pf-06647263, A Novel Efna4-Adc, In Patients With Metastatic Triple Negative Breast Cancer.

2511Background: PF-06647263 is an anti-Ephrin-A4 (EFNA4) antibody drug conjugate (ADC) composed of a humanized mAb, a hydrazone cleavable linker, and calicheamicin, a potent DNA damaging agent. Higher levels of EFNA4 expression have been shown in tumor versus normal tissue, including in two thirds of triple negative breast cancers (TNBC). In vivo preclinical studies demonstrate PF-06647263 induced tumor regression in TNBC models. Methods: In Part 1 of a dose escalation, cohorts of 2-12 patient (pts) with solid tumors that were unselected for EFNA4 expression received escalating doses of PF-06647263 once every 3 weeks (Q3W, Cohort A) or weekly (QW, Cohort B). Escalations were based on mTPI design. An expansion cohort enrolled TNBC patients (n=12) unselected for EFNA4 expression. Efficacy, safety, EFNA4 RNA expression, pharmacokinetic (PK) and anti-drug antibody development were assessed. Results: Part 1 (dose escalation):A total of 48 pts (25 in A and 23 in B) wereenrolled. The most common treatment relate...