A NOVEL ANTIBODY FOR NSCLC

As reported by Heist et al in the Journal of Clinical Oncology, the antibody-drug conjugate sacituzumab govitecan showed activity in patients with previously treated metastatic non–small cell lung cancer (NSCLC). Sacituzumab targets Trop-2, present on many solid tumors; govitecan is the active metabolite of irinotecan.

Study Details

In the multicenter study, 54 patients received sacituzumab govitecan at 8 (n = 8) or 10 mg/kg (n = 46) on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate.

Response Rates

Among 47 evaluable patients, who had a median of 3 prior therapies (range = 2–7), objective response (all partial responses) occurred in 9 patients (19%). The median response duration was 6.0 months. An additional 11 patients had stable disease for ≥ 4 months, yielding a clinical benefit rate of 43%. Among 14 patients who had received prior immune checkpoint inhibitor therapy, 2 (14%) had a response and 3 had stable disease ≥ 4 months, yielding a clinical benefit rate of 36%. Among all 54 patients, median progression-free survival was 5.2 months, and median overall survival was 9.5 months.

Among 26 evaluable archived tumor specimens, 24 (92%) were strongly or moderately positive for Trop-2 on immunohistochemistry, suggesting Trop-2 is not a biomarker of response.

Adverse Events

Grade ≥ 3 adverse events included neutropenia (28%), leukopenia (9%), pneumonia (9%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response to the agent. Adverse events appeared to be similar at the two doses, except for an increase in grade 3 or 4 neutropenia at the higher dose (30% vs 13%). Adverse events led to drug discontinuation in two patients (grade 3 pneumonia and grade 3 recurrent pruritus).

The investigators concluded: “IMMU-132 [sacituzumab govitecan] was well tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This [antibody-drug conjugate] should be studied further in this disease and in other patients with Trop-2–expressing tumors.”

The study was supported by Immunomedics.