TOPLINE

Tambotatug pelitecan, a new antibody-drug conjugate, significantly improved overall survival and progression-free survival (PFS) compared with topotecan as second-line therapy for relapsed extensive-stage small-cell lung cancer (SCLC) in a phase 3 trial conducted in China. Despite a lower overall rate of grade ≥ 3 adverse events, tambotatug pelitecan was not categorically safer than topotecan given its distinct toxicity profile, including a higher risk for interstitial lung disease/pneumonitis. 

METHODOLOGY

• Second-line treatment options for relapsed SCLC remain limited; topotecan is the standard therapy but has modest benefit and is linked to significant hematologic toxicity. Tambotatug pelitecan is a novel B7-H3-targeting antibody-drug conjugate that has shown promising efficacy in this patient population in an early-phase trial but needs further evaluation in a larger setting.
• To evaluate the safety and efficacy of tambotatug pelitecan vs topotecan as second-line therapy, researchers conducted a phase 3 randomized superiority trial involving 451 patients (median age, 62.0 years) with SCLC that had progressed or relapsed following first-line platinum-based treatment.
• Patients were randomly assigned to receive tambotatug pelitecan (n = 225), given intravenously at 2.0 mg/kg on day 1 of each 3-week cycle (capped at 200 mg/cycle), or topotecan (n = 226), given intravenously at 1.2 mg/m² on days 1-5 of each 3-week cycle; 224 patients in the tambotatug pelitecan group and 217 in the topotecan group received at least one dose and were included in the safety population.
• The primary endpoint was overall survival; secondary endpoints included PFS and objective response. Patients were followed up for a median of 9.2 months in the tambotatug pelitecan group and 9.5 months in the topotecan group.
• Overall, 96.2% of patients had systemic disease, 34.4% had a history of brain metastases at baseline, 87.1% had received previous anti-programmed death ligand 1 or anti-programmed cell death protein 1 therapy, and 48.8% had platinum-resistant disease.

TAKEAWAY

• The median overall survival was significantly longer with tambotatug pelitecan than with topotecan (13.3 vs 9.4 months; stratified hazard ratio [HR], 0.46; P < .001). This benefit extended across nearly all subgroups, including patients with systemic disease (median overall survival, 12.8 months with tambotatug pelitecan vs 8.8 months with topotecan; unstratified HR, 0.49).
• The median PFS was significantly longer with tambotatug pelitecan than with topotecan (7.4 vs 2.8 months; stratified HR, 0.29; P < .001), and a comparable PFS benefit was seen among patients with systemic disease (median PFS, 7.4 vs 2.8 months; unstratified HR, 0.32).
• Objective response was seen in 59.1% of patients receiving tambotatug pelitecan and 9.7% of those receiving topotecan (P < .001). In an exploratory analysis of 143 patients with intracranial lesions at baseline, intracranial response was also higher with tambotatug pelitecan (32% vs 3%), with longer median intracranial PFS (6.1 vs 4.2 months).
• Grade ≥ 3 adverse events occurred in fewer patients receiving tambotatug pelitecan vs topotecan (55.4% vs 77.9%), whereas serious adverse events occurred in similar percentages of patients (38.8% vs 43.3%). Common treatment-related adverse events of grade ≥ 3 with tambotatug pelitecan included neutropenia (21.0%), leukopenia (19.2%), lymphopenia (13.4%), thrombocytopenia (12.5%), and anemia (10.7%). Tambotatug pelitecan also resulted in a higher incidence of interstitial lung disease/pneumonitis (4.9% vs 1.4%).

IN PRACTICE

"These findings support the use of tambotatug pelitecan as a new second-line treatment option for relapsed small-cell lung cancer," the study authors wrote.

SOURCE

The study, led by Yuanyuan Zhao, MD, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, in Guangzhou, China, was published online in The New England Journal of Medicine.

LIMITATIONS

The study's open-label design may have led to performance bias affecting how treatment was managed and adverse events were identified. Investigator-assessed (rather than blinded, centrally reviewed) secondary end points may reflect evaluator bias. Additionally, enrollment was limited to China, and the trial population was predominantly male with a relatively high percentage of nonsmokers, limiting generalizability to more diverse populations. 

DISCLOSURES

The study was supported by a grant from the Innovative Drug Research and Development National Science and Technology Major Project and by MediLink Therapeutics. Five authors declared being employees of MediLink Therapeutics. Some authors reported research grants or personal fees from various pharmaceutical companies, including AstraZeneca, Novartis and others. Full disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.