Sanofi’s ADC is targeting CEACAM5 in patients with NSCLC

Phase I/II study of tusamitamab ravtansine (Sanofi) in patients with non-sq having locally advanced or metastatic NSCLC for which no standard alternative therapy is available.

Tusamitamab ravtansine (SAR408701) is an ADC composed of a humanized monoclonal antibody that binds carcinoembryonic antigen-related cell adhesion molecule-5 (CEACAM5) and a cytotoxic maytansinoid that selectively targets CEACAM5-expressing tumor cells.

A total of 24 patients were treated for ≥ 6 months, 15 patients for ≥ 9 months, 11 patients for ≥ 12 months, 6 patients for ≥ 24 months, and 2 patients for ≥ 42 months. At the data cutoff, 5 patients remained on treatment, 1 for > 3.5 y. For patients treated ≥ 12 months, the median treatment duration was 26.6 months.

Of 15 patients with PR in the prior analysis, as of Dec 2021, PR was still observed in 10 patients (67%) treated for ≥ 6 months, 8 patients (53%) for ≥ 9 months, and 7 patients (47%) for ≥ 12 months. For the 11 patients treated ≥ 12 months, 7 had PR, and 4 had SD. Of the 11 patients treated ≥ 12 months, 9 had high CEACAM5 expression, and 2 had moderate CEACAM5 expression; most had prior treatment with an anti-PD1/PD-L1.

Patients treated for ≥ 12 months had better ECOG performance status and fewer prior treatments than the overall group. Of patients treated for ≥ 12 months, PR occurred irrespective of CEACAM5 expression level. Only 1 patient treated for ≥ 12 months discontinued due to a treatment-emergent adverse event (TEAE). Corneal events (keratitis/keratopathy) were the most frequent TEAEs.

KOL insights

“The observed long-term clinical benefit and safety profile of Tusa support its further clinical development; a Phase III study is ongoing to evaluate Tusa monotherapy in previously treated pts with high CEACAM5 expressing NSQ NSCLC”–Expert Opinion.

Conclusion

CEACAM5 is expressed in about 20% of patients with NSCLC adenocarcinoma but is not found in normal lung tissue. This makes CEACAM5 a potentially attractive therapeutic target; therefore, it is currently being explored as a potential biomarker. Understanding CEACAM5 may potentially give us more insights to target this malignancy with a poor prognosis.

Until now, Tusamitamab ravtansine clinical trial results have been most promising in NSQ-NSCLC; in fact, it is the most advanced novel agent in clinical testing targeting CEACAM5, specifically NSLC patients. The ADC has already entered phase III development for NSCLC; moreover, it is also being evaluated in Phase II trials for Metastatic Breast and Pancreatic Cancer.

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