Background: PF-06647263 is an anti-EFNA4 antibody drug conjugate (ADC) comprised of a humanized mAb (huE22), a hydrazine linker, and calicheamicin. Ephrin-A4 (EFNA4) is overexpressed in tumor versus normal tissue in a number of human tumors. PF-06647263 induced tumor regression in triple negative breast cancer (TNBC) and ovarian cancer (OVCA) xenograft models. Methods: Patients (pts) with solid tumors unseleceted for EFNA-4 expression are receiving escalating doses of PF-06647263 once every 3 weeks (Q3W) or weekly (QW) in 2-6 patient cohorts. The following doses have been evaluated: 0.015, 0.030, 0.050, 0.075, 0.100, and 0.134 mg/kg Q3W and 0.01 and 0.02 mg/kg QW. Once the maximum tolerated dose (MTD) is determined, expansion cohorts for patients with EFNA4-expressing TNBC and platinum-resistant OVCA are planned. Standard definitions are being used to classify hematological and non-hematological dose limiting toxicities (DLT). Serum pharmacokinetic (PK) and anti-drug antibody (ADA) development are also being assessed. Results: Data are available on 24 pts treated- 15 Q3W and 9 QW. Among the 24 pts (20F/4M), the mean age was 59 years (35-82). Total number of administered cycles is 55 (Q3W) and 26 (QW), and DLTs, were observed in 0 and 1 pts in the Q3W and QW regimens, respectively, during the first cycle. The most common adverse events (AE) were nausea (50%), fatigue (50%), decreased appetite (38%), diarrhea (33%), vomiting (33%), thrombocytopenia (TCP) (33%), abdominal pain (29%), and blood bilirubin increase (29%). One patient experienced Grade 4 neutropenia and the AEs with Grade 3 severity observed in more than 2 patients were mucosal inflammation (n = 3; 12%) and bilirubin increase (n = 2; 8%). Preliminary evidence of activity includes confirmed partial response (PR) in 2 pts (OVCA and TNBC). Two additional unconfirmed PRs (TNBC and peritoneal cancer) have also been recorded. Conclusions: PF-06647263 is a novel anti-EFNA4-ADC which to-date is well-tolerated in pts with advanced malignancies. Dose-escalation is continuing and updated safety, efficacy, and preliminary PK data will be reported at the meeting. Clinical trial information: NCT02078752