Risvutatug Rezetecan Receives FDA Orphan Drug Designation for SCLC
Risvutatug rezetecan, an antibody-drug conjugate (ADC) targeting B7-H3, has received orphan drug designation from the US Food and Drug Administration (FDA) for the treatment of small cell lung cancer (SCLC). The agent consists of a human anti-B7-H3 monoclonal antibody linked to a topoisomerase inhibitor, and is being developed for the treatment of solid tumors. The designation was announced in a press release dated December 10, 2025.1
Risvutatug rezetecan received prior breakthrough therapy designation from the FDA in August 2024 for patients with extensive-stage SCLC (ES-SCLC). Both the breakthrough and orphan drug designations were supported by findings from the phase I ARTEMIS-001 trial, which evaluated the safety and efficacy of risvutatug rezetecan in patients with SCLC.
During a dose escalation phase, participants received HS-20093 at doses ranging from 1 to 16 mg/kg every 3 weeks. In the dose expansion phase, patients were assigned to receive 8 mg/kg or 10 mg/kg. All enrolled patients with ES-SCLC received at least one dose of risvutatug rezetecan, and they were required to have received prior platinum-based standard therapy. B7-H3 expression was assessed retrospectively.2>
Among patients treated with risvutatug rezetecan, the overall response rate (ORR) was 57.1% (95% CI, 34%-78.2%) and the disease control rate (DCR) was 95.2% (95% CI, 76.2%-99.9%). Median duration of response (DoR) and progression-free survival (PFS) were not applicable (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).1
Deep responses, which are defined as tumor shrinkage of 50%, were observed in 44.2% of patients. Responses occurred regardless of B7-H3 expression. The median overall survival (OS) was not reached.1
FDA Approves Subcutaneous Amivantamab and Hyaluronidase-lpuj for EGFR+ NSCLC
The FDA has approved the subcutaneous injection of amivantamab plus hyaluronidase-lpuj for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR-exon 19 mutations or exon 21 L858R substitution mutations.3 The approval was granted on December 17, 2025.4
The approval was supported by data from the phase III PALOMA-3 study, a randomized, open-label, multicenter, multiregional trial. A total of 418 patients were randomly assigned to receive either subcutaneous amivantamab and hyaluronidase-lpuj plus lazertinib or intravenous amivantamab plus lazertinib.3
Primary pharmacokinetic endpoints included trough concentrations at steady state (Ctrough), with key secondary endpoints of ORR, PFS, and overall survival (OS). At the recommended every 2-week dosing schedule, the geometric mean ratios (GMR) (90% CI) for exposure and steady-state trough concentrations demonstrated pharmacokinetic comparability between subcutaneous and intravenous formulations.3
Similarly, at the recommended every 3-week dosing schedule, simulated GMR (90%) for average concentration and steady-state Ctrough exceeded the pre-specific threshold of 0.8.3 Descriptive analyses showed no notable differences in ORR and PFS. There was no evidence of a detrimental effect on OS observed in patients who received subcutaneous amivantamab compared with those who received intravenous amivantamab formulation.3
Resources:
- 1. FDA Grants Orphan Drug Designation to Risvutatug Rezetecan in SCLC
- 2. Wang, Jie, et al. “Artemis-001: Data from a Phase 1a/B Study of HS-20093 in Patients with Relapsed Small Cell Lung Cancer (SCLC).” Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024). https://doi.org/10.1200/jco.2024.42.16_suppl.8093.
- 3. FDA approves amivantamab and hyaluronidase-lpuj for subcutaneous injection
- 4. FDA OKs Subcutaneous Amivantamab in EGFR+ NSCLC
