View in EDS

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

Saved in:
Bibliographic Details
Title: Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial
Authors: Verstovsek, Srdan, Foltz, Lynda, Gupta, Vikas, Hasserjian, Robert, Manshouri, Taghi, Mascarenhas, John, Mesa, Ruben, Pozdnyakova, Olga, Ritchie, Ellen, Veletic, Ivo, Gamel, Katia, Hamidi, Habib, Han, Lyrialle, Higgins, Brian, Trunzer, Kerstin, Uguen, Marianne, Wang, Dao, El-Galaly, Tarec Christoffer, Todorov, Boyan, Gotlib, Jason
Source: Haematologica
Haematologica, Vol 108, Iss 10 (2023)
Verstovsek, S, Foltz, L, Gupta, V, Hasserjian, R, Manshouri, T, Mascarenhas, J, Mesa, R, Pozdnyakova, O, Ritchie, E, Veletic, I, Gamel, K, Hamidi, H, Han, L, Higgins, B, Trunzer, K, Uguen, M, Wang, D, El-Galaly, T C, Todorov, B & Gotlib, J 2023, 'Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis : stage I of a phase II trial', Haematologica, vol. 108, no. 10, pp. 2730-2742. https://doi.org/10.3324/haematol.2022.282411
Publisher Information: Ferrata Storti Foundation (Haematologica), 2023.
Publication Year: 2023
Subject Terms: Anemia, Fibrosis, Recombinant Proteins, 3. Good health, Drug Therapy, Combination/adverse effects, Primary Myelofibrosis/diagnosis, Treatment Outcome, Primary Myelofibrosis, Article - Myeloproliferative Disorders, Recombinant Proteins/adverse effects, Humans, Diseases of the blood and blood-forming organs, Drug Therapy, Combination, RC633-647.5
Description: 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 α 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; investigatorassessed) 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).
Document Type: Article
Other literature type
File Description: application/pdf
ISSN: 1592-8721
0390-6078
DOI: 10.3324/haematol.2022.282411
Access URL: https://pubmed.ncbi.nlm.nih.gov/37165840
https://doaj.org/article/853c9266e7f0447385d894bbf77cd11a
https://vbn.aau.dk/ws/files/551309018/11079-Article_Text-81045-2-10-20230926.pdf
http://www.scopus.com/inward/record.url?scp=85170267143&partnerID=8YFLogxK
https://vbn.aau.dk/da/publications/965feb45-9b9b-47b0-b264-8b4ca378ee3b
https://doi.org/10.3324/haematol.2022.282411
Rights: CC BY
URL: http://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Accession Number: edsair.doi.dedup.....9bae343ac0540437338f07184e78868a
Database: OpenAIRE
Description
Abstract: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 α 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; investigatorassessed) 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).
ISSN:15928721
03906078
DOI:10.3324/haematol.2022.282411