Riz-Rez Produces Anti-Tumor Activity in Extensive-Stage SCLC

Risvutatug rezetecan (Ris-Rez), an investigational B7-H3–targeted antibody-drug conjugate (ADC), demonstrated antitumor activity and a manageable safety profile in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) in the phase 1b dose-optimization portion of the EMBOLD PanTumour-101 trial (NCT06551142), according to a news release from the developer, GSK.¹

What efficacy and safety were observed?

At the 8-mg/kg dose, Ris-Rez achieved a confirmed objective response rate (ORR) of 61% (n = 11/18; 95% CI, 35.7%-82.7%) among evaluable patients compared with 32% (n = 7/22; 95% CI, 13.9%-54.9%) at the 6-mg/kg dose. The safety profile was manageable across both dose levels at a median follow-up of 100.5 days. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 42% of patients receiving the 8-mg/kg dose and 15% of those receiving the 6-mg/kg dose, with hematologic events being the most common. The overall rate of interstitial lung disease (ILD) was low, occurring in 2% of patients (n = 1/50); that single case was grade 2.

“[ES-SCLC] cancer remains one of the most aggressive cancers we treat, with 5-year survival rates typically in the single digits,” said study investigator Hye Ryun Kim, MD, PhD, of the Division of Medical Oncology at Yonsei Cancer Center, in the news release.¹ “Patients whose disease relapses often have limited options, and current therapies can be difficult to tolerate. The response rates and manageable safety profile observed with Ris-Rez are encouraging and support its ongoing development in this setting.”

The findings represent the first global data for the agent in ES-SCLC and were to be presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.

How was EMBOLD PanTumour-101 designed?

EMBOLD PanTumour-101 is a global, open-label phase 1a/b study evaluating the safety, tolerability, and clinical activity of Ris-Rez monotherapy in adult patients with advanced or metastatic solid tumors.² In the phase 1b dose-optimization portion, patients with relapsed, second-line or later ES-SCLC were randomly assigned to receive Ris-Rez at 6 mg/kg or 8 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, loss to follow-up, or death.

The analysis included 50 patients who had received a median of 2 prior therapies, and the study population included patients with prior topoisomerase-1 inhibitor or tarlatamab-dlle (Imdelltra) exposure as well as patients with brain or liver metastases. Enrollment in the dose-optimization portion was still ongoing at the data cutoff, and the developers noted that longer follow-up will be needed to further characterize the durability of response.

What is the broader development context for Ris-Rez?

The 8-mg/kg dose selected on the basis of these data, along with data from the phase 3 ARTEMIS-008 study (NCT06498479) in SCLC, is being evaluated in GSK’s global phase 3 EMBOLD SCLC-301 study (NCT07099898).

“Today’s first global data for Ris-Rez build on the statistically significant overall survival benefit recently reported in Hansoh’s pivotal Chinese trial,” said Hesham Abdullah, senior vice president and global head of oncology, research and development, at GSK, in the news release.¹ “As the data for Ris-Rez continue to grow, we remain focused on accelerating development in [ES-SCLC], where patients often relapse quickly and urgently need more treatment options.”

Ris-Rez is an investigational ADC targeting the B7-H3 protein, which is highly expressed in more than 10 solid tumor types. The agent has received orphan drug designations in the US, Japan, and the EU for SCLC, as well as breakthrough therapy designation in the US and Priority Medicines designation from the European Medicines Agency for relapsed or refractory ES-SCLC.

What is the unmet need in ES-SCLC?

SCLC accounts for approximately 10% to 15% of all lung cancer diagnoses worldwide and is characterized by rapid progression, early metastatic spread, frequent relapse, and poor prognosis. Approximately 70% of patients with SCLC are diagnosed with extensive-stage disease, in which the cancer has spread throughout one or both lungs and/or to other parts of the body, and the median overall survival for patients with ES-SCLC treated with current standard-of-care therapies is approximately 12 to 13 months.

References

1. GSK presents first global data for Ris-Rez in extensive-stage small cell lung cancer. News release. GSK plc. October 18, 2026. Accessed October 19, 2026. https://tinyurl.com/3pusy7j6
2. A study of GSK5764227 in participants with advanced solid tumors (EMBOLD) (PanTumor-101). ClinicalTrials.gov. Updated May 22, 2026. Accessed October 19, 2026. https://tinyurl.com/46rwv7dh