Fulgenzi Claudia A M, Dalla Pria Alessia, Leone Alberto Giovanni, Martinez Maria, Del Peral Elena Ferrer Martinez, Flores Maria Eleanor, Bower Mark, Pinato David J
Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120 NN, UK.
National Centre for HIV Oncology, Chelsea Westminster Hospital, London, UK.
BMC Cancer. 2025 Jul 1;25(1):1104. doi: 10.1186/s12885-025-14326-2.
Kaposi sarcoma (KS) is a mesenchymal malignancy induced by human herpes virus-8 (HHV-8). Whilst combined anti-retroviral therapy (cART) has substantially reduced the incidence of KS in people living with HIV (PLWH), KS remains the commonest neoplasia in this population. In up to 15-20% of cases, KS fails to respond to cART. T-cells immune exhaustion is thought to play a central role in mediating KS development and progression in PLWH receiving cART. The high reliance of PD-1 in shaping the cART-refractory phenotype poses a strong rationale for the use of PD-1 blocking antibodies against KS.
StarKap is a phase Ib, open label, single arm study aiming at evaluating the safety, tolerability of dostarlimab- an anti PD-1 antibody- in cART-refractory KS. Secondary endpoint is the evaluation of overall response rates by AIDS Clinical Trial Group (ACTG) criteria complemented by RECIST v1.1 in patients with visceral disease.
The trial will enrol 20 patients in total. After completion of the screening procedures, participants will receive the first dose of dostarlimab within 28 days. Dostarlimab will be administered at the dose of 500 mg evry 3 weeks for the first 5 cycles, and at 1000 mg every 6 weeks thereafter. Treatment will continue until disease progression, unacceptable toxicity, or completion of 1 year of treatment. The first 6 patients will be enrolled in a safety-lead-in phase, if no dose-limiting toxicities (DLTs) will occur within the 21 days in the first 6 participants, trial will continue. Patients will be monitored for the emergence of adverse events until 90 days after the last dose of treatment. Tumour response will be assessed as objective response rate (ORR) at cycle 4, cycle 8 and end of treatment. Tissue, bloods, and stool samples will be collected at baseline, on treatment and at end of treatment to satisfy the related translation plan.
卡波西肉瘤（KS）是一种由人类疱疹病毒8型（HHV-8）诱导的间充质恶性肿瘤。虽然联合抗逆转录病毒疗法（cART）已大幅降低了HIV感染者（PLWH）中KS的发病率，但KS仍是该人群中最常见的肿瘤。在高达15%-20%的病例中，KS对cART无反应。T细胞免疫耗竭被认为在接受cART的PLWH中介导KS的发生和发展中起核心作用。PD-1在塑造cART难治性表型方面的高度依赖性为使用抗PD-1抗体治疗KS提供了有力的理论依据。
StarKap是一项Ib期、开放标签、单臂研究，旨在评估抗PD-1抗体度伐利尤单抗在cART难治性KS中的安全性和耐受性。次要终点是根据艾滋病临床试验组（ACTG）标准并辅以RECIST v1.1评估内脏疾病患者的总缓解率。
该试验总共将招募20名患者。在完成筛查程序后，参与者将在28天内接受第一剂度伐利尤单抗。度伐利尤单抗在最初5个周期中每3周以500mg的剂量给药，此后每6周以1000mg的剂量给药。治疗将持续到疾病进展、出现不可接受的毒性或完成1年的治疗。前6名患者将进入安全性导入期，如果前6名参与者在21天内未出现剂量限制性毒性（DLT），试验将继续进行。将对患者进行不良事件监测，直至最后一剂治疗后90天。将在第4周期、第8周期和治疗结束时评估肿瘤反应，作为客观缓解率（ORR）。将在基线、治疗期间和治疗结束时收集组织、血液和粪便样本，以满足相关的转化计划。
