TROPiCS-03 Basket Trial Results of Second-Line Sacituzumab Govitecan for Extensive-Stage SCLC

Extensive-stage small cell lung cancer (ES-SCLC) is often treated with a combination of immunotherapy and chemotherapy; however, limited treatment options are available following progression on this combination regimen, underscoring the need for novel therapies in the second-line setting. Sacituzumab govitecan (SG) is a Trop-2–directed antibody-drug conjugate that has demonstrated antitumor activity in previously treated ES-SCLC in a phase 1/2 study. Based on these encouraging results, the open-label, multicohort, phase 2 study (TROPiCS-03; NCT03964727) is evaluating SG in patients with metastatic or locally advanced solid tumors including ES-SCLC. Preliminary safety and efficacy results from the ES-SCLC cohort of the TROPiCS-03 basket trial presented at the 2023 ESMO annual meeting are summarized here.

The study included adult patients diagnosed with ES-SCLC who had progressed after ≤1 prior line of platinum-based chemotherapy and anti–PD-(L)1 therapy. Eligible patients received SG (10 mg/kg) on days 1 and 8 of a 21-day cycle. The primary end point was objective response rate (ORR) by investigator assessment per RECIST v1.1, and secondary end points were clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), progression-free survival, overall survival, and safety. Date of data cutoff was July 27, 2023.

The study population consisted of 30 patients who received ≥1 dose of SG. Median age was 67 years; the majority of patients had an Eastern Cooperative Oncology Group performance status of 1 (87%). The median follow-up was 5.1 months. The median duration on treatment was 3.9 months ,and 19 patients had discontinued study treatment at data cutoff, most commonly due to disease progression. An ORR of 37% was achieved, including 11 partial responses and 15 patients with stable disease; DCR was 87% and CBR was 40%. The median DOR was 6.3 months. Seventy-seven percent of patients with postbaseline tumor assessment had any tumor reduction and 43% of patients had a tumor reduction over 30%.

Treatment-related adverse events (TRAEs, any grade) were reported in 93% of patients; of these, grade ≥3 TRAEs occurred in 50% of patients. The most frequent grade 3 treatment-emergent adverse events were diarrhea, neutropenia, and fatigue. There were no reports of deaths or TRAEs leading to treatment discontinuations.

Based on these results, the authors concluded that SG demonstrated promising antitumor activity and manageable safety as second-line treatment for ES-SCLC.

Source:

Dowlati A. Sacituzumab govitecan (SG) as second-line (2L) treatment for extensive stage small cell lung cancer (ES-SCLC): preliminary results from the phase II TROPiCS-03 basket trial. Abstract presented at: ESMO Annual Meeting, October 20-24, 2023; Madrid, Spain. Abstract 1990MO.