FDA Grants Orphan Drug Designation to Risvutatug Rezetecan in SCLC

Results from the ARTEMIS-001 trial previously showed that the B7-H3-targeted ADC elicits deep responses in patients with ES-SCLC.

The FDA has granted orphan drug designation to risvutatug rezetecan (GSK’227), a B7-H3–targeted antibody drug conjugate (ADC), as a treatment for patients with small cell lung cancer (SCLC), according to a press release from the developer, GSK.1

Previously, in August 2024, the FDA granted breakthrough designation to risvutatug rezetecan for patients with extensive-stage SCLC (ES-SCLC).2

Both indications were supported by results from the phase 1 ARTEMIS-001 trial (NCT05276609), which evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of risvutatug rezetecan in Chinese patients with advanced solid tumors. Data from the trial were shared at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.3

As of the November 30, 2023 data cutoff date, among patients with relapsed ES-SCLC who received 8.0 mg/kg of risvutatug rezetecan (n = 31), the overall response rate (ORR) was 58.1% (95% CI, 39.1%-75.5%), and the disease control rate (DCR) was 80.6% (95% CI, 62.5%-92.5%). The median duration of response (DOR) and progression-free survival (PFS) was 4.3 months (95% CI, 3.3-not applicable [NA]) and 5.6 months (95% CI, 3.4-NA), respectively.The median follow-up was 4.8 months (95% CI, 3.6-5.6).

Among patients who received 10 mg/kg of risvutatug rezetecan (n = 21), the ORR was 57.1% (95% CI, 34.0%-78.2%), and the DCR was 95.2% (95% CI, 76.2%-99.9%). The median DOR and PFS was NA (95% CI, 3.1-NA) and NA (95% CI, 4.4-NA), respectively. The median follow-up was 4.9 months (95% CI, 4.1-5.6).

Notably, deep responses defined as tumor shrinkage of 50% or more were observed in 44.2% of patients, and responses occurred regardless of B7-H3 expression. The median overall survival (OS) was not reached. Pharmacokinetic profiles of total antibody and ADC were similar, with considerably low exposure to payload; pharmacokinetics also demonstrated dose-proportional increase in exposure with a 3-to-7-day half-life.

In the press release, the investigators noted that SCLC constitutes 13% of all lung cancers, and 70% of patients with SCLC have extensive-stage disease. For ES-SCLC, the 5-year survival rate is 3%; most patients relapse after initial treatment, and the median OS with standard-of-care treatment is about 8 months.4,5

ARTEMIS-001 consisted of a dose-escalation and a dose-expansion phase; patients were treated with risvutatug rezetecan from 1.0 to 16.0 mg/kg every 3 weeks in the dose-escalation phase, and 8.0 and 10.0 mg/kg every 3 weeks in the dose-expansion phase.

Eligible patients were 18 years or older at screening with histologically or cytologically confirmed, locally advanced or metastatic solid tumors for which standard treatment does not exist or is ineffective.6 Additional criteria included at least 1 extra-cranial measurable lesion, fresh or archival tumor tissue, at least 12 weeks of life expectancy, and an ECOG performance status of 0 or 1.

A total of 56 patients with ES-SCLC were enrolled and received at least 1 dose of risvutatug rezetecan; the median number of prior lines of therapy was 2 (range, 1-6), all patients had received prior platinum plus etoposide, and 73.2% received immunotherapy.

Regarding safety, the most common treatment-related adverse events (TRAEs) of grade 3 or higher were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia, all of which occurred in at least 10% of patients. Reportedly, the safety profile was consistent with previous reports.

Risvutatug rezetecan was also granted breakthrough therapy designation by the FDA in relapsed/refractory osteosarcoma following 2 or more prior lines of therapy in January 2025.7

References

1. GSK’227, a B7-H3-targeted antibody-drug conjugate, granted orphan drug designation in small-cell lung cancer by the US FDA. News release. GSK. December 10, 2025. Accessed December 10, 2025. https://tinyurl.com/2c2ve3ue
2. GSK receives US FDA Breakthrough Therapy Designation for its B7-H3-targeted antibody-drug conjugate in relapsed or refractory extensive-stage small-cell lung cancer. News release. GSK. August 20, 2024. Accessed December 10, 2025. https://tinyurl.com/4e2yecs7
3. Wang J, Duan J, Sun Y, et al. ARTEMIS-001: data from a phase 1a/b study of HS-20093 in patients with relapsed small cell lung cancer (SCLC). J Clin Oncol. 2024;42(suppl 16):8093. doi:10.1200/JCO.2024.42.16_suppl.8093
4. SEER Explorer Surveillance Research Program. National Cancer Institute. Accessed December 10, 2025. https://tinyurl.com/ykz89kpf
5. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393(4):349-361. doi:10.1056/NEJMoa2502099
6. ARTEMIS-001: phase 1 study of the HS-20093 in patients with advanced solid tumors. ClinicalTrials.gov. Updated February 15, 2023. Accessed December 10, 2025. https://tinyurl.com/4829ej6s
7. GSK’s B7-H3-targeted antibody-drug conjugate, GSK’227, receives US FDA breakthrough therapy designation in late-line relapsed or refractory osteosarcoma. News release. GSK. January 7, 2025. Accessed January 8, 2025. https://tinyurl.com/5n6zx9vb