Sacituzumab Govitecan Earns Breakthrough Therapy Designation in ES-SCLC

Sacituzumab govitecan showed promising response and survival data in the extensive-stage small cell lung cancer cohort of the phase 2 TROPiCS-03 trial.

Sacituzumab govitecan-hziy (Trodelvy) has been granted the breakthrough therapy designation by the FDA for the treatment of adult patients who have extensive-stage small cell lung cancer (ES-SCLC) and have experienced disease progression on or following platinum-based chemotherapy, according to a press release from the developer, Gilead.¹

The trial agent is the first, and only, currently approved Trop-2–directed antibody-drug conjugate to demonstrate meaningful survival data in multiple types of metastatic breast cancer.

Supporting data for the decision emerged from the ES-SCLC cohort of the phase 2 TROPiCS-03 study (NCT03964727) that investigated the efficacy of sacituzumab govitecan in patients with metastatic solid tumors. The primary end point was objective response rate (ORR) assessed per RECIST v1.1 criteria.

“Treatment options for patients with relapsed SCLC are limited,” lead study author Afshin Dowlati, MD, professor in the department of Medicine, Division of Hematology and Oncology at Case Western Reserve University School of Medicine, and fellow authors wrote in a presentation given at the 2024 IASLC World Conference on Lung Cancer (WCLC).² “[Sacituzumab govitecan] showed promising efficacy as a second-line treatment for patients with ES-SCLC…These encouraging data warrant further investigation of sacituzumab govitecan in ES-SCLC in a randomized phase 3 study.”

At the data cutoff, median follow-up was 12.3 months (range 8.1-20.1). The ORR was 41.9% (95% CI, 27.0%-57.9%) for all 43 patients included in the analysis. Confirmed partial responses (PR) were observed in 18 (41.9%) patients; stable disease in 18 (41.9%) patients; progressive disease in 4 (9.3%) patients; and the remaining 3 (7.0%) patients were not assessed. The disease control rate was 83.7% (95% CI, 69.3%-93.2%), and the clinical benefit rate was 48.8% (95% CI, 33.3%-64.5%).

The median duration of response (DOR) was 4.7 months (95% CI, 3.5-6.7). At 6 months, the DOR rate was 48.2% (95% CI, 23.9%-68.9%). Median time to response was 1.4 months (range, 1.2-4.2).

Median progression-free survival (PFS) was 4.40 months (95% CI, 3.81-6.11), and median overall survival (OS) was 13.60 months (95% CI, 6.57-14.78).

Positive antitumor activity was shown in both patients who had platinum-resistant (n = 20) and platinum-sensitive (n = 23) disease, with ORRs of 35.0% (95% CI, 15.4%-59.2%) and 47.8% (95% CI, 26.8%-69.4%), respectively.

Median duration of treatment was 4.4 months (range, 0.03-18.04), and median number of cycles received was 7 (range, 1-25). A total of 36 (83.7%) patients discontinued study treatment; disease progression leading to treatment discontinuation was cited as the most common reason, occurring in 31 (72.1%) patients.

A total of 43 patients in the ES-SCLC cohort were included in the analysis and received 10 mg/kg of intravenous sacituzumab govitecan on days 1 and 8 of each 21-day cycle until progressive disease or unacceptable toxicity.

Key eligibility criteria included histologically confirmed ES-SCLC, disease progression after 1 prior line of platinum-based chemotherapy and anti–PD-L1 therapy, an ECOG performance status of 0 or 1, and measurable disease per RECIST v1.1 guidelines. Patients with stable and treated brain metastases were allowed.

The median age of patients was 67 years (range, 48-83). Per chemotherapy-free interval (CTFI), 20 (46.5%) patients were platinum-resistant (CTFI of less than 90 days), and 23 (53.5%) patients were platinum-sensitive (CTFI of 90 days or more). Furthermore, 40 (93.0%) patients had stage IV disease at initial diagnosis; 13 (30.2%) and 5 (11.6%) had metastatic disease present in the liver and brain, respectively.

Regarding safety, grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 32 (74.4%) patients, and serious TEAEs occurred in 22 (51.2%) patients. The most common TEAEs of grade 3 or higher were neutropenia (44%), diarrhea (9%), and anemia (5%). Additionally,16 (37.2%) patients experienced TEAEs that led to dose reduction, no patients had TEAEs that led to treatment discontinuation, and 3 patients experienced TEAEs leading to death, 1 (2.3%) of which was related to the study drug.

References

1. U.S. FDA grants breakthrough therapy designation to Trodelvy® (sacituzumab govitecan-hziy) for second-line treatment of extensive-stage small cell lung cancer. News release. Gilead. December 17, 2024. Accessed December 18, 2024. https://tinyurl.com/55fv6m8v
2. Dowlati A, Chiang AC, Cervantes A, et al. Sacituzumab govitecan as second-line treatment in patients with extensive-stage small cell lung cancer. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract #OA04.04.