Activity and Safety of Geptanolimab (GB226) for patients with unresectable, recurrent or metastatic alveolar soft part sarcoma: a phase 2 single-arm study
Mené sur 37 patients atteints d’un sarcome alvéolaire des tissus mous, récidivant ou métastatique et non résécable, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité du geptanolimab, un anticorps anti-PD-1
Purpose: Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized PD-1 antibody, for patients with unresectable, recurrent or metastatic ASPS. Patients and methods: We did this multicentre, single-arm, phase 2 study (Gxplore-005,NCT03623581) in patients aged 18-75 years who had unresectable, recurrent or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population. Results: Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. 14 (37.8%, 95% confidence interval [CI] 22.5-55.2) of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI 5.0-not reached) and disease control was achieved in 32 (86.5%, 95% CI 71.2-95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anaemia, hypophysitis and proteinuria (one each [2.7%]). No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAE (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response (P=0.031). Conclusions: Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent or metastatic ASPS.