Safety and efficacy of tusamitamab ravtansine (SAR408701) in long-term treated patients with nonsquamous non–small cell lung cancer (NSQ NSCLC) expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)

9039 Background: Tusamitamab ravtansine (tusa) is a novel antibody-drug conjugate that selectively targets CEACAM5, a cell surface glycoprotein highly expressed in several tumor types. In previously reported results from an open-label Phase 1/2 study (NCT02187848), tusa showed promising antitumor activity in patients (pts) with heavily pretreated NSQ NSCLC and high CEACAM5 expression (Gazzah A et al. J Clin Oncol. 2020;38[15 suppl]:9505). Herein we report results for pts treated for ≥ 12 mo with NSQ NSCLC and high or moderate CEACAM5 expression. Methods: In the Phase 1/2 study, 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 100 mg/m2 Q2W. As of Jan 2020, among CEACAM5 high expressors, 13 had confirmed partial response (PR) and 28 had stable disease (SD); among moderate expressors, 2 had PR and 15 had SD. We focus here on pts treated ≥ 12 mo as of Dec 2021. Results: A total of 24 pts were treated for ≥ 6 mo, 15 pts for ≥ 9 mo, 11 pts for ≥ 12 mo, 6 pts for ≥ 24 mo, and 2 pts for ≥ 42 mo. At the data cutoff, 5 pts remained on treatment, 1 for > 3.5 y. For pts treated ≥ 12 mo median (range) treatment duration was 26.6 (12.1–45.3) mo. Of 15 pts with PR in the prior analysis, as of Dec 2021 PR was still observed in 10 pts (67%) treated for ≥ 6 mo, 8 pts (53%) for ≥ 9 mo, and 7 pts (47%) for ≥ 12 mo. For the 11 pts treated ≥ 12 mo, 7 had PR and 4 had SD. Of the 11 pts treated ≥ 12 mo, 9 had high CEACAM5 expression and 2 had moderate CEACAM5 expression; most had prior treatment with an anti-PD1/PD-L1. Pts treated for ≥ 12 mo had better ECOG performance status and fewer prior treatments than the overall group. Of pts treated for ≥ 12 mo, PR occurred irrespective of CEACAM5 expression level. Only 1 pt treated for ≥ 12 mo discontinued due to a treatment emergent adverse event (TEAE) (breast cancer). Corneal events (keratitis/keratopathy) were the most frequent TEAEs, occurring in 8 pts (73%); 4 pts (36%) with Grade ≥ 3; 7 pts had subsequent treatment modification (delay or delay/reduced dose). No corneal TEAE was serious or led to treatment discontinuation. Conclusions: 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. No patient discontinued long-term treatment because of drug-related toxicity. Corneal toxicity in these pts was manageable with dose modification (delay/reduction). The observed long-term clinical benefit and safety profile of tusa support its further clinical development; a Phase 3 study is ongoing to evaluate tusa monotherapy in previously treated pts with high CEACAM5 expressing NSQ NSCLC. Clinical trial information: NCT02187848.