Abstract

Background

MIRACULUM (NCT03269565) is a multicenter open-label parallel-arm phase II study investigating the antitumor activity of prolgolimab, an IgG1 anti-PD-1 monoclonal antibody with Fc silencing “LALA” mutation, in patients with advanced melanoma. Final analysis after ≥12 months of follow-up is presented.

Methods

Patients (pts) with unresectable or metastatic melanoma, without autoimmune disease, no prior BRAF/MEK inhibitors, and anti-PD-1 or anti-CTLA-4 therapy were eligible. Pts received prolgolimab 1 mg/kg Q2W (arm 1) or 3 mg/kg Q3W (arm 2) until disease progression or intolerable toxicity. A statistical hypothesis that prolgolimab has significant anti-tumor effect (ORR more than 28%) was tested for each study arm.

Results

126 pts (63 in each arm) received at least one dose of prolgolimab (mITT population). Baseline pt characteristics were generally balanced between the arms. Prior systemic therapy was administered in 17 (27%) and 16 (25%) pts in arm 1 and 2, respectively. Stage II-III unresectable disease was observed in 4 (6.4%) pts in arm 1 and in 2 (3.2%) pts in arm 2. As of Feb 22, 2019, median follow-up was 13.8 mo (95%CI, 13.2-14.7) in arm 1 and 14.5 mo (95%CI, 13.9-15.2) in arm 2. The study met its primary endpoint in both study arms. In arm 1, 38% ORR was achieved, including 5 CR and 19 PR, and the disease control rate (DCR) was 64%. In arm 2, 29% ORR was achieved, including 2 CR and 16 PR, and the DCR was 46%. 12-mo OS rates were 74.6% for 1 mg/kg Q2W and 54.0% for 3 mg/kg Q3W. 12-mo PFS rates were 41.3% for 1 mg/kg Q2W and 34.9 for 3 mg/kg Q3W. Median response duration was not reached; 83% of all responses were ongoing at data cutoff. Treatment-related AEs (TRAEs) occurred in 55.6% and 54.0% of pts, including 12.7% and 3.2% with grade 3-4 TRAEs in arm 1 and 2, respectively. Immune-related AEs (irAEs) occurred in 36.5% of pts in arm 1 and 34.9% of pts in arm 2, including 7.4% and 1.6% of pts with grade 3/4 irAEs in each arm.

Conclusion

Both dosing regimens of prolgolimab (1 mg/kg Q2W and 3 mg/kg Q3W) have durable antitumor activity and a manageable safety profile in patients with advanced melanoma.

Clinical trial identification

NCT03269565.

Legal entity responsible for the study

BIOCAD.

Funding

BIOCAD.

Disclosure

S. Tjulandin: Advisory / Consultancy, Speaker Bureau / Expert testimony: BIOCAD. M. Fedyanin: Advisory / Consultancy, Speaker Bureau / Expert testimony: BIOCAD. L. Demidov: Advisory / Consultancy, Speaker Bureau / Expert testimony: BIOCAD. V. Moiseyenko: Research grant / Funding (institution): BIOCAD. S. Protsenko: Advisory / Consultancy, Speaker Bureau / Expert testimony: BIOCAD. S. Odintsova: Speaker Bureau / Expert testimony: BIOCAD. T.Y. Semiglazova: Advisory / Consultancy, Speaker Bureau / Expert testimony: BIOCAD. M. Nechaeva: Speaker Bureau / Expert testimony: BIOCAD. O. Kozlova: Full / Part-time employment: BIOCAD. M. Shustova: Full / Part-time employment: BIOCAD. A. Garipov: Full / Part-time employment: BIOCAD. R. Ivanov: Full / Part-time employment: BIOCAD. All other authors have declared no conflicts of interest.

中文翻译：

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119P新型PD-1抑制剂proggolimab II期试验（MIRACULUM）在晚期黑素瘤患者中的最终结果

抽象的

背景

MIRACULUM（NCT03269565）是一项多中心开放标签平行臂II期研究，研究了具有Fc沉默“ LALA”突变的IgG1抗PD-1单克隆抗体prolgolimab对晚期黑色素瘤患者的抗肿瘤活性。随访≥12个月后进行最终分析。

方法

患有不可切除或转移性黑色素瘤，无自身免疫性疾病，既往没有BRAF / MEK抑制剂以及抗PD-1或抗CTLA-4治疗的患者（pts）是合格的。Pt接受普罗戈利单抗1 mg / kg Q2W（第1组）或3 mg / kg Q3W（第2组），直到疾病进展或无法忍受的毒性。对每个研究组检验了普罗戈利单抗具有显着的抗肿瘤作用（ORR超过28％）的统计假设。

结果

126名患者（每组63人）接受了至少一剂普罗戈利单抗（mITT人群）。两组之间的基线pt特征通常保持平衡。先前的全身治疗分别在第1臂和第2臂分别进行了17（27％）和16（25％）分的患者。在第1组中有4（6.4％）分，在第2组中有2（3.2％）分，观察到II-III期不可切除疾病。截至2019年2月22日，中位随访时间为13.8 mo（95％CI，13.2）手臂1中的-14.7）和手臂2中的14.5 mo（95％CI，13.9-15.2）（该研究在两个研究手臂中均达到了其主要终点）。在第1组中，ORR达到38％，包括5 CR和19 PR，疾病控制率（DCR）为64％。在第2组中，ORR达到29％，包括2 CR和16 PR，DCR为46％。1 mg / kg Q2W的12个月OS率为74.6％，3 mg / kg Q3W的OS为54.0％。1 mg / kg Q2W时12个月PFS率为41.3％，3 mg / kg Q3W时为34.9。未达到中位反应持续时间；所有答复中有83％正在进行数据截止。与治疗相关的AEs（TRAEs）发生于患者的55.6％和54.0％，其中臂1和2的3-4级TRAEs分别发生了12.7％和3.2％。免疫相关的AEs（irAEs）发生在第1组的36.5％的患者和第2组的34.9％的患者，包括每组的3/4级irAE的7.4％和1.6％的患者。

结论

普罗戈利单抗的两种给药方案（1 mg / kg Q2W和3 mg / kg Q3W）均具有持久的抗肿瘤活性，并且对于晚期黑色素瘤患者具有可控的安全性。

临床试验鉴定

NCT03269565。

负责研究的法人实体

BIOCAD。

资金

BIOCAD。

揭露

S. Tjulandin：发言人办公室咨询/顾问/专家证词：BIOCAD。M. Fedyanin：发言人局咨询/顾问/专家证词：BIOCAD。L. Demidov：发言人局咨询/顾问/专家证词：BIOCAD。V. Moiseyenko：研究资助/资助（机构）：BIOCAD。S. Protsenko：发言人办公室的咨询/顾问/专家证词：BIOCAD。S. Odintsova：发言人办公室/专家证词：BIOCAD。TY Semiglazova：发言人办公室咨询/顾问/专家证词：BIOCAD。M. Nechaeva：发言人办公室/专家证词：BIOCAD。O. Kozlova：全职/兼职：BIOCAD。M. Shustova：全职/兼职：BIOCAD。答：加里波夫：全职/兼职：BIOCAD。R. Ivanov：全职/兼职：BIOCAD。所有其他作者都声明没有利益冲突。