Efficacy and safety of the antibody-drug conjugate (ADC) SAR408701 in patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC) expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).

9505 Background: We report updated safety and efficacy of DM4-conjugated anti-CEACAM5 ADC from the expansion part of the first-in-human study (NCT02187848; Gazzah A et al. J Clin Oncol. 2019;37:15, 9072) in 92 NSQ NSCLC pts. Methods: CEACAM5 expression was assessed by immunohistochemistry on archived tumor samples. Two cohorts of pts have been analyzed: moderate and high expressors, with CEACAM5 expression at ≥2+ intensity between ≥1% to < 50% and ≥50% of the tumor cell population, respectively. SAR408701 was administered at 100 mg/m 2 IV every 2 weeks. Tumor assessments were done every 4 cycles (8 weeks). Primary endpoint was overall response rate (ORR). Results: As of January 2020, 92 pts were treated: 28 moderate and 64 high expressors, with median age 62.5 years (31–91; 42.4% of pts ≥65), 51.1% male, 71.7% ECOG PS ≥1; median of 3 prior treatments (1–10 lines) for advanced disease, including anti-tubulin agents (60.9%) and anti-PD1/PD-L1 (75%). In the moderate expressor cohort, 2 confirmed partial responses (PR) were observed (ORR 7.1%). In the high expressor cohort, 13 pts had confirmed PRs (ORR 20.3% [95% confidence interval 12.27%–31.71%]); 27 (42.2%) had stable disease; ORR of 17.8% was observed in 45 pts who had prior anti-PD1/PD-L1. Pts had a median of 7 (1–49) cycles; median relative dose intensity was 0.98. Six pts discontinued due to treatment-emergent adverse events (TEAEs). Most frequent TEAEs (all grades) were asthenia (38.0%), keratopathy/keratitis (38.0%), peripheral neuropathy (26.1%), dyspnea (23.9%), and diarrhea (22.8%). 31 pts had dose modification due to a TEAE, including dose reduction for keratopathy/keratitis in 10 pts. Hematological toxicity included leukopenia (14.4%), neutropenia (4.4%), and thrombocytopenia (13.3%). Grade ≥3 TEAEs occurred in 47.8% of pts and were assessed as drug-related in 15.2%. Conclusions: SAR408701 shows promising antitumor activity in heavily pretreated advanced NSQ NSCLC pts with high CEACAM5 expression. SAR408701 was well tolerated, with minimal hematological toxicity compared to conventional chemotherapy; keratopathy was reversible and manageable with dose modification. These data support the activity of SAR408701 in NSQ NSCLC CEACAM5 high expressors. A phase 3 trial evaluating the activity of CEACAM5-DM4 ADC monotherapy in comparison with docetaxel in NSQ NSCLC CEACAM5 high expressors after failure of standard first line chemotherapy and anti-PD1/PD-L1 is underway. Clinical trial information: NCT02187848 .