Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial

被引：9

作者：

Verstovsek, Srdan ^{[1
,12
]}

Foltz, Lynda ^{[2
]}

Gupta, Vikas ^{[2
,3
]}

Hasserjian, Robert ^{[4
]}

Manshouri, Taghi ^{[1
]}

Mascarenhas, John ^{[5
]}

Mesa, Ruben ^{[6
]}

Pozdnyakova, Olga ^{[7
]}

Ritchie, Ellen ^{[8
]}

Veletic, Ivo ^{[1
]}

Gamel, Katia ^{[9
]}

Hamidi, Habib ^{[10
]}

Han, Lyrialle ^{[10
]}

Higgins, Brian ^{[10
]}

Trunzer, Kerstin ^{[9
]}

Uguen, Marianne ^{[9
]}

Wang, Dao ^{[9
]}

El-Galaly, Tarec Christoffer ^{[9
,13
]}

Todorov, Boyan ^{[9
]}

Gotlib, Jason ^{[11
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[2] Univ British Columbia, St Pauls Hosp, Vancouver, BC, Canada

[3] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada

[4] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA

[5] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[6] UT Hlth San Antonio MD Anderson, Mays Canc Ctr, San Antonio, TX USA

[7] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[8] Weill Cornell Med, New York, NY USA

[9] F Hoffmann La Roche Ltd, Basel, Switzerland

[10] Genentech Inc, San Francisco, CA USA

[11] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA USA

[12] Kartos Therapeut Inc, Redwood City, CA USA

[13] Aalborg Univ Hosp, Dept Hematol, Aalborg, Denmark

来源：

HAEMATOLOGICA | 2023年 / 108卷 / 10期

关键词：

INTERNATIONAL WORKING GROUP; MYELOPROLIFERATIVE NEOPLASMS RESEARCH; BONE-MARROW FIBROSIS; SERUM-AMYLOID-P; PULMONARY-FIBROSIS; AVAILABLE THERAPY; LUNG FIBROSIS; IWG-MRT; FEDRATINIB; LONG;

D O I：

10.3324/haematol.2022.282411

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Pentraxin 2 (PTX-2; serum amyloid P component), a circulating endogenous regulator of the inflammatory response to tissue injury and fibrosis, is reduced in patients with myelofibrosis (MF). Zinpentraxin alfa (RO7490677, PRM-151) is a recombinant form of PTX-2 that has shown preclinical antifibrotic activity and no dose-limiting toxicities in phase I trials. We report results from stage 1 of a phase II trial of zinpentraxin alfa in patients with intermediate-1/2 or high-risk MF. Patients (n=27) received intravenous zinpentraxin alpha weekly (QW) or every 4 weeks (Q4W), as monotherapy or an additional therapy for patients on stable-dose ruxolitinib. The primary endpoint was overall response rate (ORR; investigator -assessed) adapted from International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria. Secondary endpoints included modified Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) change, bone marrow (BM) MF grade reduction, pharmacokinetics, and safety. ORR at week 24 was 33% (n=9/27) and varied across individual cohorts (QW: 38% [3/8]; Q4W: 14% [1/7]; QW+ruxolitinib: 33% [2/6]; Q4W+ruxolitinib: 50% [3/6]). Five of 18 evaluable patients (28%) experienced a >= 50% reduction in MPN-SAF TSS, and six of 17 evaluable patients (35%) had a >= 1 grade improvement from baseline in BM fibrosis at week 24. Most treatment-emergent adverse events (AE) were grade 1-2, most commonly fatigue. Among others, anemia and thrombocytopenia were infrequent (n=3 and n=1, respectively). Treatment-related serious AE occurred in four patients (15%). Overall, zinpentraxin alfa showed evidence of clinical activity and tolerable safety as monotherapy and in combination with ruxolitinib in this open-label, non-randomized trial (clinicaltrials gov. Identifier: NCT01981850).

引用

页码：2730 / 2742

页数：13