132613-144

A phase I study of DNIB0600A, an antibody-drug conjugate (ADC) targeting NaPi2b, in patients (pts) with non-small cell lung cancer (NSCLC) or platinum-resistant ovarian cancer (OC).

Category: 
Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics
Session Type and Session Title: 
Oral Abstract Session, Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics
Abstract Number: 
2504
Citation: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 2504)
Author(s): 
Howard A. Burris, Michael S. Gordon, David E. Gerber, David R. Spigel, David S. Mendelson, Joan H. Schiller, Yulei Wang, Younjeong Choi, Robert S. Kahn, Katie Wood, Daniel J. Maslyar, Jeffrey R. Infante; Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; Premiere Oncology of Arizona, Scottsdale, AZ; The University of Texas Southwestern Medical Center, Dallas, TX; Sarah Cannon Research Institute, Nashville, TN; Pinnacle Oncology Hematology, Scottsdale, AZ; Genentech Inc, South San Francisco, CA; Genentech, Inc., South San Francisco, CA; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: NaPi2b (SLC34A2) is a multi-transmembrane, sodium-dependent phosphate transporter expressed in ~70% non-squamous NSCLC and ~90% OC. DNIB0600A is an ADC consisting of a humanized IgG1 anti-NaPi2b monoclonal antibody conjugated to an anti-mitotic agent MMAE that shows anti-proliferative activity in xenograft models . Methods: This study evaluated safety and activity of DNIB0600A (0.2-2.8 mg/kg) given by intravenous infusion every 3 weeks (q3w) to pts with NSCLC or platinum-resistant OC. A traditional 3+3 design was used for dose escalation followed by expansion at the recommended Phase 2 dose (RP2D) of 2.4 mg/kg in patients with NSCLC and OC. Tumor NaPi2b expression was evaluated by immunohistochemistry (IHC) in archival tissue. Results: As of 10 Dec 2013, 73 pts have enrolled (43 NSCLC; 30 OC), median age 62 (range 39-85), PS 0-1, median number of prior regimens 3 (1-10) in NSCLC, and 5 (1-12) in OC. Pts received a median of 4 (range 1-28) cycles of DNIB0600A. One pt experienced a DLT (Grade 3 dyspnea) at 1.8 mg/kg; no additional DLTs occurred through the maximally administered dose of 2.8 mg/kg. The most common related AEs (all grades) were fatigue (55%), nausea (40%), peripheral neuropathy (36%), decreased appetite (34%), vomiting (26%), and alopecia (19%). Related Grade 3/4 adverse events included neutropenia (8%), anemia, peripheral neuropathy, and pneumonia (each 3%), dehydration, dyspnea, fatigue, hyperglycemia, hyperkalemia, hypertensions, transaminitis, and URI (each 1%)— only dyspnea led to study treatment discontinuation. At the RP2D of 2.4 mg/kg q3w, 7/17 (41%) of IHC 2/3+ pts with OC had confirmed PRs (DoR range 1.4+ to 9.4+ months). In NSCLC, 2/21 (10%) of IHC 2/3+ pts had confirmed PRs (DoR 4.3 and 4.8 months), and 5/21 (24%) had unconfirmed PRs for best response. No pt with an IHC Score of 0 showed clinical response by RECIST criteria. + : censored. Conclusions: DNIB0600A administered q3w has an encouraging safety profile and evidence of anti-tumor activity in both OC and NSCLC. These data support Phase 2 development in OC with further clinical evaluation of DNIB0600A in NSCLC. Clinical trial information: NCT01375842..