Relapsed small cell lung cancer (SCLC) remains a major therapeutic challenge, with limited treatment options and poor outcomes after disease progression on platinum-based chemotherapy and immunotherapy. At the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC), results from two randomized phase III trials evaluated B7-H3–directed antibody-drug conjugates (ADCs) against topotecan. Both studies demonstrated significant improvements in overall survival, progression-free survival, and response rates, accompanied by manageable safety profiles, highlighting the emerging role of this drug class in relapsed SCLC.
TAISHAN-302
The phase III TAISHAN-302 trial found that tambotatug pelitecan (Tam-Peli, YL201), a novel anti–B7-H3 ADC, significantly improved overall survival, progression-free survival, and objective response rate compared with topotecan in patients with SCLC (Abstract PL02.03).
Topotecan has long been a standard second-line treatment for SCLC, but its survival benefit remains modest. TAISHAN-302 evaluated Tam-Peli as a second-line treatment for patients whose SCLC had relapsed after first-line therapy.
The randomized, open-label study enrolled 451 patients, with 225 assigned to receive Tam-Peli and 226 assigned to receive topotecan. Patients receiving Tam-Peli were treated with 2.0 mg/kg intravenously on day 1 of each 3-week cycle, with a maximum dose of 200 mg. Treatment continued until disease progression or unacceptable toxicity. The study's primary endpoint was overall survival, with progression-free survival and objective response rate as key secondary endpoints.
As of May 20, 2026, after a median follow-up of 9.4 months, median overall survival was 13.3 months with Tam-Peli compared with 9.4 months with topotecan. Tam-Peli reduced the risk of death by 54% (hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.35–0.62, P < .0001). The survival benefit was consistent across prespecified subgroups, including patients with brain metastases, liver metastases, and a chemotherapy-free interval of less than 90 days.
Tam-Peli also significantly improved progression-free survival. Median progression-free survival was 7.4 months with Tam-Peli vs 2.8 months with topotecan, representing a 71% reduction in the risk of disease progression or death (HR = 0.29, 95% CI = 0.23–0.37, P < .0001). The objective response rate was 59.1% with Tam-Peli compared with 9.7% with topotecan (P < .0001).
The safety profile of Tam-Peli was considered manageable and consistent with its known profile, with no new safety signals identified. Grade 3 or higher treatment-related adverse events occurred in 46.4% of patients receiving Tam-Peli compared with 74.7% receiving topotecan, and there were no treatment-related deaths in the Tam-Peli arm. Treatment-emergent interstitial lung disease or pneumonitis occurred in 4.9% of patients receiving Tam-Peli and 1.4% receiving topotecan; grade 3 events occurred in 0.9% of patients in each group, with no grade 4 or 5 events reported.
“TAISHAN-302 is among the first phase III studies of an ADC to demonstrate statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and objective response rate compared with topotecan in relapsed SCLC,” said presenting author Li Zhang, MD, of Sun Yat-sen University Cancer Center. “Together with a generally favorable and manageable safety profile, these results support Tam-Peli as a potential new standard-of-care option for second-line SCLC and may reshape the treatment landscape for this challenging disease.”
ARTEMIS-008
Results from the randomized phase III ARTEMIS-008 trial show that risvutatug rezetecan (Ris-Rez), a B7-H3–directed ADC, significantly improved overall survival compared with topotecan in patients with relapsed SCLC whose disease progressed on or after platinum-based chemotherapy (Abstract PL02.04).
ARTEMIS-008 (ClinicalTrials.gov NCT06498479) is an ongoing multicenter, open-label, randomized phase III study. A total of 461 patients in China were randomly assigned 1:1 to receive Ris-Rez 8.0 mg/kg every 3 weeks or topotecan at 1.2 mg/m² on days 1 through 5 every 3 weeks. More than 80% of patients had previously received PD-1/-L1 inhibitors. The primary endpoint was overall survival, with progression-free survival, objective response rate, disease control rate, and safety among the key secondary endpoints.
At the June 6th, 2026, data cutoff, after a median follow-up of 12.2 months, median overall survival was 18.5 months with Ris-Rez compared with 10.3 months with topotecan. Ris-Rez reduced the risk of death by 54% (HR = 0.46, 95% CI = 0.35–0.62, P < .0001), with consistent overall survival benefits across relevant subgroups.
Blinded independent central review also favored Ris-Rez across key secondary efficacy measures. Median progression-free survival was 7.2 months with Ris-Rez vs 3.0 months with topotecan (HR = 0.33, 95% CI = 0.25–0.42). The objective response rate was 58.3% vs 12.6%, respectively, and the disease control rate was 90.4% vs 60.2%. Investigator-assessed outcomes were consistent with the central review findings.
Grade 3 or higher treatment-related adverse events occurred less frequently with Ris-Rez than with topotecan, at 60.9% vs 78.2%. The most common grade 3 or higher treatment-related adverse events were hematologic toxicities, including decreased neutrophil count, decreased white blood cell count, anemia, decreased lymphocyte count, and decreased platelet count.
“Ris-Rez demonstrated a statistically significant and clinically meaningful overall survival benefit over topotecan in patients with SCLC that progressed after platinum-based therapy, with a favorable safety profile,” said presenting author Jie Wang, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, China. “These results suggest the potential of Ris-Rez to define a new standard of care in relapsed SCLC.”
DISCLOSURE: For full disclosures of the study authors, visit abstractsonline.com.
