Ris-rez plus adebrelimab led to an approximate 50% response rate and durable disease control in pretreated nonsquamous NSCLC without actionable mutations.
A novel combination targeting B7-H3 and PD-L1 demonstrated encouraging efficacy in previously treated patients with advanced nonsquamous non–small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs), according to data from the expansion cohort of the phase 1 ARTEMIS-101 trial (NCT05276609) that were presented during the
At a median follow-up of 11.7 months, 44.1% (n = 15) of patients remained on treatment with risvutatug rezetecan (GSK5764227/HS-20093; ris-rez) plus adebrelimab. The median progression-free survival (PFS) was 14.0 months (95% CI, 11.2-not evaluable [NE]) in 34 evaluable patients; the 12-month PFS rate was 67.7% (95% CI, 45.8%-82.3%). The median overall survival (OS) was not reached ([NR] 95% CI, NE-NE).
The confirmed objective response rate (ORR) was 47.1% (95% CI, 29.8%-64.9%), and the median duration of response (DOR) was 12.6 months (95% CI, 10.9-NE). The disease control rate (DCR) was 94.1% (95% CI, 80.3%-99.3%).
Efficacy was also similar across B7-H3 expression levels and prior immunotherapy exposure, with confirmed ORRs of 52.2% and 44.4% in immunotherapy-exposed and immunotherapy-naive patients, respectively.
“Ris-rez in combination with adebrelimab demonstrated encouraging antitumor activity in previously treated nonsquamous NSCLC without AGAs, representing clinically meaningful efficacy over historical benchmarks for both ris-rez monotherapy and docetaxel,” Runbo Zhong, PhD, lead study author and medical doctor at Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine in Shanghai, China, and Jilin Cancer Hospital in Changchun, China, said in a presentation of the data. “Efficacy was observed across B7-H3/PD-L1 expression levels and regardless of prior anti–PD-(L)1 exposure,” Zhong added.
B7-H3 is an immune checkpoint protein that is upregulated in lung cancer, among others. Because of its limited expression in healthy tissues and correlation with reduced survival, investigators believe B7-H3 may represent an ideal therapeutic target.
Ris-rez is a fully human anti–B7-H3 IgG1 monoclonal antibody linked to a topoisomerase 1 inhibitor payload via a protease-cleavable linker. Adebrelimab is a fully human anti–PD-L1 IgG4 monoclonal antibody approved in China for the frontline treatment of patients with extensive-stage SCLC.
To date, ris-rez has shown single-agent activity in SCLC and NSCLC, as well as other solid tumors. In the ARTEMIS-101 trial, an 8.0-mg/kg dose of ris-rez led to a confirmed ORR of 33.3% and median PFS of 7.0 months in previously treated patients with nonsquamous NSCLC without AGAs (n = 39).2
Trial investigators enrolled patients who were at least 18 years old and had received a diagnosis of nonsquamous NSCLC without AGAs with progression or intolerance after platinum-based therapy, with measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.1
Treatment consisted of an 8.0-mg/kg dose of ris-rez plus 20.0 mg/kg of intravenous adebrelimab every 3 weeks. These doses had been selected by the safety review committee following completion of the dose-escalation phase.
Efficacy end points included ORR, DCR, DOR, PFS, and OS.
Forty patients were included in the safety set, and 34 were included in the efficacy-evaluable set. The data cutoff was January 20, 2026.
The median follow-up was 11.1 months (range, 0.7-14.5). The median age was 64.0 years (range, 39-73), and most patients were male (n = 30; 75.0%); all had adenocarcinoma. The median body mass index was 23.0 kg/m2 (range, 17.1-31.1), and most patients were either never- (n = 17; 42.5%) or former smokers (n = 21; 52.5%). TNM stage at screening was III (n = 4; 10.0%) or IV (n = 36; 90.0%), and most patients had an ECOG performance status of 1 (n = 35; 87.5%).
In terms of therapy, the median number of prior lines was 1 (range, 1-2) and included chemotherapy (n = 40; 100.0%), immunotherapy (n = 30; 75.0%), antiangiogenic therapy (n = 18; 45.0%), and a topoisomerase 1–based antibody-drug conjugate (n = 2; 5.0%).
Brain metastases (n = 5; 12.5%) and liver metastases (n = 3; 7.5%) were present in the minority of patients. Data on PD-L1 expression level were not available in 40.0% (n = 16) of patients; 15 (37.5%) and 9 (22.5%) had a tumor proportion score (TPS) of less than 1% and 1% or greater, respectively.
The median treatment exposure was 8.5 months for both riz-rez (range, 1-21) and adebrelimab (range, 1-20).
“Antitumor activity was observed across PD-L1 subgroups but was shown to be numerically higher in PD-L1–positive patients,” Zhong said.
In the PD-L1 TPS less than 1 subgroup (n = 15), the confirmed ORR was 33.3% (95% CI, 11.8%-61.6%), with partial response (PR), stable disease (SD), and progressive disease (PD) rates of 33.3% (n = 5), 60.0% (n = 9), and 6.7% (n = 1), respectively. The median DOR was NR (95% CI, NE-NE), and the DCR was 93.3% (95% CI, 68.1%-99.8%). The median PFS was NR (95% CI, 4.2 months-NE), and the 12-month PFS rate was 53.6% (95% CI, 16.8%-80.4%).
In the PD-L1 TPS 1 or greater subgroup (n = 8), the confirmed ORR was 62.5% (95% CI, 24.5%-91.5%), with PR, SD, and PD rates of 62.5% (n = 5), 25.0% (n = 2), and 12.5% (n = 1), respectively. The median DOR was 12.6 months (95% CI, NE-NE), and the DCR was 87.5% (95% CI, 47.3%-99.7%). The median PFS was 14.0 months (95% CI, 1.5 months-NE), and the 12-month PFS rate was 87.5% (95% CI, 38.7%-98.1%).
Treatment-related adverse effects (TRAEs) occurred in all patients (n = 40) and were grade 3 or greater in 70.0% of cases. Serious AEs occurred in 37.5% of patients. TRAEs leading to dose reduction, dose delay, and treatment discontinuation occurred in 20.0%, 47.5%, and 15.0% of patients, respectively.
The most common grade 3 or greater TRAEs occurring in at least 25% of patients were decreased white blood cell count (30.0%), decreased neutrophil count (30.0%), decreased lymphocyte count (30.0%), and anemia (25.0%).
“Ris-rez plus adebrelimab showed a manageable safety profile, with no new safety signals identified,” Zhong said. “Hematologic toxicities [such as] neutropenia, leukopenia, lymphopenia, and anemia were the most common AEs and were readily manageable,” he added.
Any-grade TRAEs included increased alanine aminotransferase level (25.0%), vomiting (30.0%), hyponatremia (30.0%), increased aspartate aminotransferase level (32.5%), decreased lymphocyte count (37.5%), decreased appetite (47.5%), hypoalbuminemia (47.5%), asthenia (52.5%), decreased platelet count (52.5%), pyrexia (57.5%), nausea (62.5%), decreased neutrophil count (75.0%), decreased white blood cell count (80.0%), and anemia (87.5%).
All treatment-related interstitial lung disease events were grade 1 or 2 (n = 4; 10.0%), and no treatment-emergent AE led to death.
“Based on these preliminary safety and efficacy results, a phase 3 study [NCT07464327] of ris-rez plus adebrelimab in nonsquamous NSCLC without AGAs is currently underway,” Zhong concluded.3
Disclosures: Zhong had no financial relationships to disclose; he shared that the study was funded by Shanghai Hansoh BioMedical Co, Ltd.
