2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
First-in-human phase 1 study of the antibody-drug conjugate (ADC) SAR408701 in advanced solid tumors: Dose-expansion cohort of patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #395)
J Clin Oncol 37, 2019 (suppl; abstr 9072)
Author(s): Anas Gazzah, Sophie Cousin, Valentina Boni, Charles Ricordel, Tae Min Kim, Jin-Soo Kim, Carole Helissey, Itziar Gardeazabal, Mustapha Chadjaa, Aurore Allard, Semra Yoruk, Fabrice Barlesi; Department of Drug Development (DITEP), Gustave Roussy, Villejuif Cedex, France; Institut Bergonié, Bordeaux, France; START Madrid-Centro, Madrid, Spain; Service de Pneumologie, CHU Rennes, Rennes, France; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea; Clinical Research Unit, Department of medical oncology, HIA Bégin, Saint-Mandé, Paris, France; Vall D’Hebron Institute of Oncology, Barcelona, Spain; Sanofi R&D, Oncology, Vitry-Sur-Seine, France; Sanofi, Chilly-Mazarin, France; Sanofi, Istanbul, Turkey; Aix Marseille University, INSERM, CNRS, CRCM, APHM, CEPCM CLIP2, Marseille, France
Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell-surface glycoprotein highly expressed in several tumor types. This Phase 1, open-label, dose-escalation, dose-expansion study (NCT02187848) investigated SAR408701, a DM4 conjugated ADC targeting CEACAM5, in pts with advanced solid tumors. During dose escalation, maximum tolerated dose (MTD) of SAR408701 was 100 mg/m2 IV once every 2 weeks in 14-day cycles. Interim analysis of an ongoing expansion cohort in pts with NSQ NSCLC with CEACAM5 expression in ≥ 50% of the tumor cell population is reported. Methods: SAR408701 was administered at MTD. Primary endpoint: overall response rate (ORR; expansion phase). Secondary endpoints include safety and pharmacokinetics (PK). Tumor assessments were performed every 4 cycles (8 weeks). Results: As of Aug 2, 2018, 22 pts with NSQ NSCLC (21 adenocarcinoma; 1 not yet reported) received SAR408701 at MTD. Median age: 60 years; male: 72.7%; ECOG PS (n = 21): 0 = 38.1%, 1 = 61.9%. Median number of prior anticancer therapies for advanced disease was 3; 66.7% (14/21) received ≥ 3 lines; 59.1% had prior anti-tubulin-based treatments. Pts received a median of 6.5 cycles. 15 pts discontinued due to progressive disease and 1 due to an adverse event (AE; peripheral neuropathy); 6 pts remain on study. ORR was estimated at 22.7% (5/22 pts; 90% CI 11.5–39.9); 40.9% had stable disease. Most frequently occurring all-grade treatment-emergent AEs (TEAEs) were corneal events (40.9%; including keratitis 22.7% [1 Grade 3] and keratopathy 18.2%), dyspnea (31.8%; 5 Grade ≥ 3), asthenic conditions (31.8%) and diarrhea (27.3%). 6 pts had ≥ 1 dose modification due to a TEAE. PK analysis was performed in 14 pts at Cycle 1; mean Cmax, AUC, clearance and t1/2z were 53.1 µg/mL, 297 µg.day/mL, 0.685 L/day and 6.19 days, respectively. Conclusions: In pts with advanced NSQ NSCLC and CEACAM5 expression in ≥ 50% of tumor cells, SAR408701 had a favorable safety profile. Interim analysis of 22 pts achieved the predefined boundary for efficacy (≥ 4 of 30 pts). These data support further development in NSQ NSCLC. Funding: Sanofi Clinical trial information: NCT02187848