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P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P3.11-014 - Safety, pharmacokinetics, and activity of the anti-NaPi2b antibody-drug conjugate DNIB0600A: A Phase I study in patients with non-small cell lung cancer and platinum-resistant ovarian cancer (ID 1477)
09:30 - 16:30 | Author(s): J. Schiller
NaPi2b (SLC34A2) is a multi-transmembrane, sodium-dependent phosphate transporter highly expressed in non-small cell lung cancer (NSCLC) and ovarian cancer (OC). DNIB0600A is an antibody-drug conjugate consisting of a humanized anti-NaPi2b IgG1 monoclonal antibody and the anti-mitotic agent MMAE.
This study evaluated safety, pharmacokinetics (PK), and pharmacodynamics of DNIB0600A (0.2-2.8 mg/kg) given every 3 weeks (q3w) to patients (pts) with non-squamous NSCLC or platinum-resistant, non-mucinous OC. A traditional 3+3 design was used for dose escalation followed by expansions in NSCLC and OC at the recommended Phase 2 dose (RP2D). Tumor NaPi2b expression was evaluated in archival tissue by immunohistochemistry (IHC). Anti-tumor activity was evaluated per RECIST 1.1.
As of 1 May 2013, 65 pts have enrolled (35 NSCLC; 30 OC), median age 62 (range 39-85), PS 0-1, median number of prior regimens 2 (1-8) in NSCLC pts, and 5 (1-12) in OC pts. Pts received a median of 4 (range 1-25) doses of DNIB0600A. One pt experienced a DLT (Grade 3 dyspnea) at 1.8 mg/kg; however, no additional DLTs occurred through the maximally administered dose of 2.8 mg/kg. Two patients had Grade 1 and 2 infusion-related reactions. The most common related AEs (all grades) were fatigue (55%), nausea (35%), peripheral neuropathy (32%), decreased appetite (29%), vomiting (25%), alopecia (20%), and diarrhea, dysgeusia, headache, and pain (each 15%). The majority of these AEs were Grade 1 and Grade 2. Two patients had serious AEs (SAE) which led to discontinuation (dyspnea; dehydration and hyperglycemia). Four other related SAEs (nausea, upper respiratory tract infection, abdominal pain, and headache) were noted in 2 pts. Preliminary PK results support a q3w dosing regimen with no accumulation observed. Expansion at 2.4 mg/kg was selected based on cumulative safety data and a benefit/risk assessment performed at time of expansion. Exposures of analytes monitored were dose-proportional over all dose levels, and no PK difference was observed between NSCLC or OC pts. Approximately 60% of NSCLC and 90% of OC pts expressed high levels (IHC 2+/3+) of NaPi2b. Anti-tumor activity with DNIB0600A was associated with tumor NaPi2b expression for both NSCLC and OC. Of the 40 pts with NaPi2b IHC Score of 2+ or 3+, treated at dose levels 1.8-2.8 mg/kg, 10 pts had a confirmed partial response (PR); 2 of 18 NSCLC and 8 of 22 OC pts, respectively. Additionally, 3 NSCLC and 3 OC pts have unconfirmed PRs. No pt was enrolled with NaPi2b IHC Score of 1+; no pt responded among the 13 pts with NaPi2b IHC Score of 0, treated at dose levels 1.8-2.8 mg/kg
DNIB0600A administered q3w has an encouraging safety, tolerability, and PK profile and evidence of anti-tumor activity in NSCLC and OC pts whose tumors express NaPi2b detectable by IHC. This data supports further clinical evaluation of DNIB0600A in NSCLC and OC together with a companion diagnostic.
PL03 - Presidential Symposium Including Top Rated Abstracts (ID 85)
- Event: WCLC 2013
- Type: Plenary Session
- Presentations: 1
PL03.07 - Treatment with Therapies Matched to Oncogenic Drivers Improves Survival in Patients with Lung Cancers: Results from The Lung Cancer Mutation Consortium (LCMC) (ID 2444)
08:15 - 09:45 | Author(s): J. Schiller
Detecting and targeting the oncogenic drivers EGFR and ALK have transformed the care of patients with lung adenocarcinomas. The LCMC was established to use multiplexed assays to test tumors for alterations in 10 genes and provide the results to clinicians to select treatments and clinical trials matched to the driver detected.
Fourteen LCMC sites enrolled patients with metastatic lung adenocarcinomas and tested their tumors in CLIA laboratories for activating mutations in 10 oncogenic driver genes.
Tumors were tested from 1,007 patients for at least one gene and 733 for all 10 genes. An oncogenic driver was found in 466 (64%) of fully-genotyped cases. Among these 733 tumors, drivers found were: KRAS 182 (25%), sensitizing EGFR 122 (17%), ALK rearrangements 57 (8%), “other” EGFR 29 (4%), two genes 24 (3%), HER2 19 (3%), BRAF 16 (2%), PIK3CA 6 (1%), MET amplification 5 (1%), NRAS 5 (1%), MEK1 1 (<1%), AKT1 0. For cases with any genotyping, we used results to select a targeted therapy or trial in 275 (28%). Among 938 patients with follow-up, the median survivals were 3.5 years for the 264 with an oncogenic driver treated with genotype-directed therapy, 2.4 years for the 318 with an oncogenic driver with no genotype-directed therapy, and 2.1 years for the 360 with no driver identified (p<0.0001).
Individuals with lung cancers with oncogenic drivers receiving a corresponding targeted agent lived longer than similar patients who did not. An actionable driver was detected in 64% of tumors from patients with lung adenocarcinomas; more than one was present in 3%. Multiplexed testing aided physicians in choosing therapies and targeted trials in 28% of patients. This paradigm for care and research will expand as genotyping becomes more efficient with Next-Gen platforms, additional drivers are identified (i.e.ROS1 and RET), and more targeted drugs become available in the pharmacy and through clinical trials. Supported by HSS NIH NCI 1RC2CA148394-01. Trial Registered with Clinicaltrials.gov: NCT01014286.
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