A phase I/II study showed tusamitamab ravtansine antitumor activity in pretreated patients (pts) with advanced nonsquamous NSCLC and high CEACAM5 expression. Here, we explore biomarker associations with tumor CEACAM5 expression by immunohistochemistry (IHC), and whether biomarkers predict objective response rate (ORR)....Pts received tusamitamab ravtansine 100 mg/m2 IV every 2 weeks….Confirmed partial responses were seen in 13/64 HEs (ORR 20.3%) and 2/28 MEs (ORR 7.1%)….In CEACAM5 HEs, high cCEA was associated with numerically greater ORR vs low cCEA (41.7% vs 8.1%).

92 pts with heavily pretreated NSQ NSCLC and high (n = 64) or moderate (n = 28) CEACAM5 expression (≥ 2+ intensity in ≥ 50% of tumor cells or in ≥ 1% to < 50% of tumor cells, respectively) were treated with tusa...Of pts treated for ≥ 12 mo, PR occurred irrespective of CEACAM5 expression level….Almost half (47%) of pts who achieved a PR were treated for ≥ 1 y, suggesting that response to tusa in heavily pretreated pts was durable and frequently sustained.

ORR was estimated at 22.7% (5/22 pts; 90% CI 11.5–39.9); 40.9% had stable disease….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).

CEACAM5 expression was assessed by immunohistochemistry on archived tumor samples.... In the high expressor cohort, 13 pts had confirmed PRs...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

...in 12 of these NSQ-NSCLC models, more tumor responses to tusamitamab ravtansine occurred in CEACAM5 HE (5/8; 62.5%) versus moderate or negative expression (1/4; 25%), including 3 with KRAS mutations among the 6 responders.