Targeting B7-H3 with antibody-drug conjugates (ADCs) could offer a major advance for patients with relapsed small cell lung cancer (SCLC), according to interim analyses from two phase 3 trials presented at the World Conference on Lung Cancer (WCLC) 2026 in Seoul, Korea.

In separate randomized trials, tambotatug pelitecan (Tam-Peli; YL201) and risvutatug rezetecan (Ris-Rez) each significantly improved overall survival, progression-free survival, and tumor response compared with topotecan, a long-standing second-line option for SCLC.

Remarkably, both trials reported a 54% reduction in the risk for death with each agent, noted Anne Chiang, MD, PhD, associate director of the Yale Cancer Center in New Haven, Connecticut, who served as discussant for the presentations.

Putting the two studies into context, Chiang said the results provide compelling evidence that B7-H3 ADCs are poised to become an important part of the relapsed SCLC treatment landscape.

“In my opinion, there is a new standard emerging,” she told attendees.

Why B7-H3?

B7-H3 is an immune checkpoint and tumor-associated antigen that’s expressed on SCLC cells and thought to contribute to tumor proliferation and inhibition of cytotoxic T cells and natural killer cells. High B7-H3 expression has been associated with worse survival in SCLC. While the antigen is found in tumors and their vasculature, it has relatively low expression in healthy tissue — making it an attractive drug target.

The phase 3 TAISHAN-302 trial put one such agent, Tam-Peli, to the test. Researchers randomly assigned 451 patients with SCLC that had progressed after one prior line of platinum-based therapy to either Tam-Peli (2.0 mg/kg intravenous [IV] every 3 weeks, maximum dose 200 mg) or topotecan (1.2 mg/m² IV on days 1-5 every 3 weeks). Most patients had previously received immunotherapy, and roughly one third had brain metastases. Overall survival was the primary endpoint.

At a median follow-up of about 9 months, median overall survival with Tam-Peli was 13.3 months vs 9.4 months with topotecan, representing a 54% reduction in the risk for death (hazard ratio [HR], 0.46; P < .0001). Median progression-free survival was 7.4 months vs 2.8 months — a 71% reduction in the risk for progression or death (HR, 0.29; P < .0001).

The confirmed objective response rate was 59.1% vs 9.7% with Tam-Peli vs topotecan. Among patients with brain metastases, intracranial progression-free survival was 6.1 vs 4.2 months, and intracranial response rates were 32.4% vs 2.9%.

Patients receiving the ADC also had fewer grade 3 or higher treatment-related adverse events, at a rate of about 46% vs 75% with topotecan. The most common were hematologic toxicities, with lower incidences observed in the Tam-Peli group. Just under 5% of patients in the ADC arm developed interstitial lung disease (ILD)/pneumonitis compared with 1.4% in the topotecan arm; grade 3 events occurred in 0.9% of each group, with no grade 4 or 5 cases.

Like Chiang, presenter Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, suggested that a new treatment era is emerging.

“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,” Zhang said in a conference news release.

Another ADC, Consistent Results

Similarly encouraging findings were reported from ARTEMIS-008, the phase 3 trial investigating Ris-Rez. There, 461 patients with relapsed SCLC were randomly assigned to either Ris-Rez (8.0 mg/kg IV every 3 weeks) or topotecan (same schedule used in the TAISHAN trial). More than 80% of patients had previously received PD-L1 inhibitors. Stable brain metastases were permitted, and overall survival was the primary endpoint.

At a median follow-up of about 12 months, median overall survival reached 18.5 months vs 10.3 months with Ris-Rez vs topotecan (HR, 0.46; P < .0001). The survival benefit was consistent across relevant subgroups, reported Jie Wang, MD, of the National Cancer Center and Chinese Academy of Medical Sciences Peking Union Medical College in Beijing, China.

Blinded independent central review also favored Ris-Rez across key secondary endpoints: Median progression-free survival was 7.2 months vs 3 months with Ris-Rez vs topotecan. 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.

As in TAISHAN, grade 3 or higher treatment-related adverse events were less common among patients receiving the ADC, at 61% vs 78% with topotecan. ILD was more common in the ADC arm, affecting roughly 12% vs 2% of patients — including grade 3 events in 4% vs 1%. No grade 4 or 5 ILD cases were reported.

Wang said the results support Ris-Rez as another potential new standard of care for relapsed SCLC and provide further rationale for the ongoing global phase 3 EMBOLD SCLC-301 trial.

A Crowded Landscape?

Chiang said it’s noteworthy that both trials demonstrated significant survival advantages over topotecan, with benefits seen across predefined subgroups, including patients with brain metastases and platinum-resistant disease. Chiang also highlighted the lower rates of severe adverse events with the ADCs, although ILD remains an important toxicity to monitor, she noted.

However, Chiang cautioned against cross-trial comparisons: TAISHAN-302 included more patients with poor prognostic features, including platinum-resistant disease and brain and liver metastases. She also noted that the trials were conducted exclusively in China and included about 30% never smokers, potentially limiting generalizability to Western populations.

More broadly, Chiang said the B7-H3 ADC field could become more crowded very soon, with ifinatamab deruxtecan under FDA priority review for extensive-stage SCLC. The FDA action date is October 10, 2026.

The treatment landscape in SCLC is “changing in real time,” Chiang said. “Stay tuned.”

TAISHAN-302 was sponsored by MediLink Therapeutics (Suzhou, China) Co., Ltd. Zhang disclosed various relationships with AstraZeneca, MSD, Novartis, and Bristol Myers Squibb. ARTEMIS-008 was sponsored and funded by Shanghai Hansoh BioMedical Co., Ltd. Wang had no disclosures. Chiang disclosed relationships with AbbVie, Amgen, AstraZeneca, Daiichi Sankyo, and other pharmaceutical companies.