You are here
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).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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..
Abstracts by Howard A. Burris:
Pertuzumab + trastuzumab for HER2-amplified/overexpressed metastatic colorectal cancer (mCRC): Interim data from MyPathway.Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 676
Pertuzumab + trastuzumab for HER2-positive metastatic biliary cancer: Preliminary data from MyPathway.Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 402
Atezolizumab (atezo) in patients with metastatic urothelial carcinoma (mUC): A 2-year clinical update from a phase Ia study.Meeting: 2017 Genitourinary Cancers Symposium | Abstract No: 290