490P Safety and efficacy of tusamitamab ravtansine in patients with colorectal or gastric cancer expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)

Abstract

In the first-in-human study of tusamitamab ravtansine (NCT02187848), an anti-CEACAM5 antibody-drug conjugate, 100 mg/m2 every 2 weeks (Q2W) showed antitumor activity in heavily pretreated patients with nonsquamous non-small cell lung cancer with high CEACAM5 expression. In the dose-escalation phase, 2 of 18 patients with colorectal cancer (CRC) and 1 of 7 with gastric cancer (GC) had confirmed partial responses (PR). Here, we report results from the CRC and GC dose-expansion cohorts. Patients were ≥ 18 years with refractory CRC (all comers) or GC. In the GC cohort, inclusion was restricted to those with high CEACAM5 expression (≥ 2+ intensity in ≥ 50% of tumor cells, as assessed by immunohistochemical analysis of tumor tissue). All patients received tusamitamab ravtansine 100 mg/m2 Q2W. The primary efficacy endpoint was overall objective response. Time to progression (TTP) and treatment-emergent adverse events (AEs) were also assessed. As of November 19, 2020, 46 patients with CRC and 16 with GC were treated. In the CRC cohort, the median age was 62 years (range, 36–77; 32.6% ≥ 65 years) and 84.1% of patients had high CEACAM5 expression. In the GC cohort, the median age was 59 years (range, 35–77; 37.6% ≥ 65 years). Patients in the CRC and GC cohorts had a median of 4 and 3 prior regimens. In the CRC cohort, the best overall response (BOR) was stable disease (SD) in 12 patients (26.1%) and a median TTP of 1.8 months (95% confidence interval [CI], 1.64–1.91). One patient had an unconfirmed PR. In the GC cohort, the BOR was SD in 6 patients (37.5%) and a median TTP of 1.7 months (95% CI, 1.18-2.60). Treatment-related AEs occurred in 34 (73.9%) and 9 (56.3%) patients in the CRC and GC cohorts. Corneal AEs (keratitis and keratopathy) occurred in 13 (28.3%) and 2 (12.5%) patients in the CRC and GC cohorts, leading to treatment modification in 5 (10.9%) patients and 1 (6.3%) patient. Grade ≥ 3 corneal AEs occurred in 2 patients with CRC and none with GC. Corneal toxicity was manageable with dose delay or modification. Tusamitamab ravtansine was well tolerated in patients with CRC or GC.