Anti-CD25 antibody(Jiangsu Hengrui )

Outcomes in classic Hodgkin lymphoma (cHL) have steadily improved; however, additional therapies are needed for patients who relapse or do not respond to novel agents. Here, we report the efficacy and safety of camidanlumab tesirine (Cami), an anti-CD25 antibody-drug conjugate, in patients with relapsed/refractory cHL after brentuximab vedotin/programmed cell death protein 1 inhibitor therapies from the phase 2 ADCT-301-201 study. Eligible patients were adults with cHL who had received ≥3 previous lines of systemic therapy (or ≥2 if ineligible for hematopoietic stem cell transplant). Patients received 45 μg/kg Cami (IV, once every 3 weeks) in cycles 1 to 2, followed by 30 μg/kg IV once every 3 weeks for ≤1 year. The primary end point was overall response rate (ORR) per 2014 Lugano classification. Secondary end points included complete response rate (CRR), progression-free survival (PFS), and overall survival (OS). In total, 117 patients were enrolled with a median age of 37.0 years (range, 19-87). The ORR was 70.1% (95% confidence interval [CI], 60.9-78.2), with a CRR of 33.3% (95% CI, 24.9-42.6). The median PFS was 9.13 months (95% CI, 5.3-15.0); median OS was not reached. Thirty-three (28.2%) patients discontinued treatment because of treatment-emergent adverse events; the most common reasons were skin and subcutaneous tissue disorders (n = 10 [8.5%] patients), infections and infestations (n = 5 [4.3%]), and nervous systems disorders (n = 5 [4.3%]). Guillain-Barré–type or polyradiculopathy-type events occurred in 8 (6.8%) patients. Cami was efficacious in this heavily pretreated population; however, the efficacy was overshadowed by substantial issues with the safety profile. This trial was registered at www.clinicaltrials.gov as #NCT04052997.

Although PD-1 checkpoint inhibition has improved outcomes for some cancer types, a substantial proportion of solid tumors still do not respond, in part due to inadequate cytotoxic CD8+ T-cell infiltration and survival within the tumor microenvironment (TME). CD25+ regulatory T-cells (Tregs) are a subset of T-cells that play a key role in suppressing CD8+ T-cell activity. Depletion of Tregs in the TME could thus enhance anti-cancer immune responses. Here, we present the experience of a patient with platinum-resistant ovarian carcinoma who achieved a durable partial response on a phase 1 clinical trial of an anti-CD25 antibody-drug conjugate combined with pembrolizumab. Notably, her tumor response correlated with a reduction in CD25+ Tregs on paired tumor biopsies and further deepened after treatment discontinuation. This case provides early proof-of-concept that Treg depletion combined with PD-1/PD-L1 inhibitors can lead to anti-cancer efficacy in refractory diseases and offers key lessons to guide future development of anti-Treg therapeutics.