An open-label, single-arm, dose escalation and expansion phase 1 study of tebotelimab (MGD013) plus niraparib in patients with locally advanced or metastatic gastric cancer who failed prior treatments.

• DOI: 10.1200/jco.2023.41.4_suppl.402
• Publication Date: 2023-01-24T21:05:07Z
• Authors: Miaozhen Qiu; Hongming Pan; Ka On Lam; Jufeng Wang; Yi Zheng; Huiyan Luo; Yu Zheng; Xiaoa Zhen; Wenzhao Hang; Jianmei Hou; Rui-hua Xu
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

402 Background: Immune checkpoint inhibitor monotherapy has limited efficacy in patients (pts) with previously treated advanced gastric cancer (GC). LAG-3 is upregulated GC pts and therefore treatment targeting may be effective. Tebotelimab a first-in-class, Fc-bearing bispecific tetravalent DART molecule that can bind both PD-1 LAG-3. Meanwhile, synergistic antitumor activities of tebotelimab niraparib, poly (ADP-ribose) polymerase inhibitor, were demonstrated preclinical studies. Methods: This open-label, single-arm, dose escalation expansion, phase 1 trial explored dose-limiting toxicities (DLTs), recommended 2 (RP2D), safety, preliminary activity plus niraparib locally or metastatic who failed ≥2 prior systemic treatments. The followed 3+3 design. Niraparib was administered orally once daily (QD) at fixed, individualized starting doses (ISD; 300 mg if baseline body weight ≥77 kg platelet count ≥150,000/µL; 200 otherwise). (120 [dose level 1], 2], 600 3]) intravenously every two weeks (Q2W) on days 15 each 28-day cycle. expansion cohort received RP2D. Results: At data cut-off as 26 Feb 2022, 27 (escalation 12, 15), whom, 7.4% PD-L1 positive (combined score ≥1) 63.0% (moderate/high expression). In the phase, no DLT observed RP2D determined Q2W ISD QD. Across phases (n=27), most common emergent adverse events (TEAEs) included nausea (63.0%), anemia (59.3%), decreased appetite (51.9%), (37.0%), hypoalbuminemia (33.3%), vomiting aspartate aminotransferase increased (29.6%), constipation (29.6%). Grade ≥3 TEAEs occurred 18 (66.7%) serious 12 (44.4%), treatment-related death. Immune-related (55.6%), hypothyroidism five (18.5%), arthralgia, hyperthyroidism, immune-related thyroiditis, rash (7.4%). target lesions (n=19), one confirmed partial response per RECIST v1.1 nine had stable disease, 5.3% overall rate 52.6% disease control rate. (n=21), medians for progression-free survival 2.7 6.5 months, respectively, after median follow-up 7.7 months. Conclusions: preliminarily an acceptable safety profile GC, however activity. No further clinical trials are planned. Clinical information: NCT04178460 .