Dr Jie Wang, ARTEMIS-008Treatment with the B7-H3-directed antibody-drug conjugate risvutatug rezetecan (Ris-Rez) results in significant improvements in overall survival (OS) compared with topotecan in patients with relapsed small-cell lung cancer (SCLC) who had progressed after receiving platinum-based chemotherapy, as shown by the results of the phase III ARTEMIS-008 trial.
“At this pre-planned interim analysis, Ris-Rez demonstrated statistically significant and clinically meaningful OS benefit over topotecan in relapsed SCLC who progressed after platinum-based therapy, with consistent benefit across all predefined subgroups,” said study co-author and presenter Dr Jie Wang, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
In ARTEMIS-008, Wang and her team randomized a total of 461 adults with SCLC who had relapsed following first-line platinum-based chemotherapy with or without immune checkpoint. Eligible patients had measurable lesions per RECIST 1.1 and an Eastern Cooperative Oncology Group performance score of 0/1. Those with stable brain metastases were also included in the study.
Of the eligible patients, 230 (median age 61.5 years) received Ris-Rez 8.0 mg/kg every 3 weeks and 231 (median age 63.0 years) topotecan 1.2 mg/m2 on days 1 through 5 every 3 weeks. Brain metastases were present in 19.1 percent and 19.9 percent of participants, respectively. Baseline characteristics were balanced between the two treatment groups.
Survival benefit
OS was the primary endpoint, while progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were secondary outcomes.
At data cutoff (6 June 2026), 77 (33.5 percent) OS events were observed in the Ris-Rez group and 121 (52.4 percent) in the topotecan group. The median OS over a median follow-up of 12.2 months was significantly higher with Ris-Rez than with topotecan (18.5 vs 10.3 months; hazard ratio [HR], 0.46, 95 percent confidence interval [CI], 0.35‒0.62; p<0.0001).
Furthermore, the 12-month OS rate was significantly higher in the Ris-Rez group than in the topotecan group (64.5 percent vs 43.3 percent), and this benefit persisted across predefined subgroups.
“With statistically significant and clinically meaningful OS benefit, the ARTEMIS-008 trial positions Ris‑Rez as a potential new standard of care for relapsed SCLC,” Wang said.
Secondary outcomes
Likewise, the median PFS by blinded independent central review (BICR) was significantly higher with Ris-Rez than with topotecan (7.2 vs 3.0 months; HR, 0.33, 95 percent CI, 0.25‒0.42). At 12 months, the PFS rate by BICR was 26.1 percent and 5.3 percent, respectively.
Other secondary outcomes also showed similar results. The ORR was 58.3 percent with Ris-Rez vs 12.6 percent with topotecan, and the DCR was 90.4 percent vs 60.2 percent, respectively. Four patients treated with Ris-Rez and none with topotecan had a complete response.
In terms of safety, Ris-Rez had a favourable safety profile with no new safety signals. Grade ≥3 treatment-related adverse events (TRAEs) occurred less frequently in the Ris-Rez group than the topotecan group (60.9 percent vs 78.2 percent). Haematologic toxicities, including decreased neutrophil, white blood cell, lymphocyte, and platelet counts and anaemia, were the most common TRAEs.
However, the rate of interstitial lung disease events was higher with Ris-Rez than with topotecan (11.7 percent vs 1.9 percent).
“These data provide critical evidence supporting the ongoing global phase III EMBOLD-SCLC-301 study in relapsed SCLC and, together with the previously reported ARTEMIS-101 results in previously treated nonsquamous, non-SCLC, reinforce the broad potential of Ris-Rez across lung cancer settings,” said Wang. [Cancer Res 2026;86(8_Suppl):abstract nr CT038]