touchHAEMATOLOGY coverage of data presented at EHA 2024:
The phase 2 KER050-MD-201 trial investigates elritercept, an activin receptor ligand trap, for treating lower-risk myelodysplastic neoplasms (LR-MDS) with anaemia. The study, as of September 2023, involved 79 participants, evaluating safety, tolerability, and response to treatment. Most participants experienced mild-to-moderate adverse events, with dyspnea and diarrhoea being most common. Of those evaluated for at least 24 weeks (N=60), half achieved haematological improvement or transfusion independence, particularly those with lower erythropoietin levels. Responses were durable, with 72% maintaining independence beyond 24 weeks. Elritercept shows promise for addressing LR-MDS and improving quality of life. Further updates will provide long-term data.
Prof. María Díez Campelo (Universidad de Salamanca, Salamanca, Spain) presented “Durable Clinical Benefit With Elritercept (KER-050) Treatment: Findings From An Ongoing Phase 2 Trial In Participants With Lower-Risk MDS” (Abstract S183) at the 29th European Hematology Association (EHA) 2024 Congress on 13–16th June 2024 in Madrid, Spain.
Associated abstracts:
- Díez Campelo M, et al. Durable Clinical Benefit With Elritercept (KER-050) Treatment: Findings From An Ongoing Phase 2 Trial In Participants With Lower-Risk MDS. European Hematology Association (EHA) 2024 Annual Congress. Abstract S183.
- Harrison C, et al. Elritercept (KER-050) Demonstrated Potential To Treat Myelofibrosis And Mitigate Ruxolitinib-Associated Cytopenias In The Phase 2 RESTORE Trial. European Hematology Association (EHA) 2024 Annual Congress. Abstract S223.
- Insert link to Claire Harrison’s video when available.
- Tan S, et al. Activin A Inhibition By Elritercept (KER-050) Is Associated With Evidence Of Cardiovascular Benefit: Translation Of Preclinical Observations To Humans With MDS. European Hematology Association (EHA) 2024 Annual Congress. Abstract P760.
- Valcárcel D, et al. Reduced Ferritin And Increased Bone Specific Alkaline Phosphatase In Participants With Lower-Risk MDS Treated With Elritercept (KER-050) Support Potential To Rebalance The Osteohematopoietic Niche. European Hematology Association (EHA) 2024 Annual Congress. Abstract S302.
Disclosures: María Díez Campelo discloses acting on advisory board for BMS, Novartis, Blueprint Medicines, GSK, Agios, Hemavan, Syros; Keros, Curis, Astex/Otsuka; and receiving honoraria/honorarium from BMS; Novartis and Keros.
This content has been developed independently by Touch Medical Media for touchHAEMATOLOGY. It is not affiliated with the European Hematology Association (EHA). Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. No endorsement of unapproved products or unapproved uses is either made or implied by mention of these products or uses by Touch Medical Media or any sponsor. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Transcript:
Hi, I’m María Díez Campelo, a haematologist at the University Hospital of Salamanca in Spain, and I am mainly focused on patients with myelodysplastic syndromes.
Can you summarize the mode of action of elritercept, and discuss the background and aims of the ongoing phase II trial of elritercept in patients with lower-risk myelodysplastic syndromes (MDS)? (0:17)
Elritercept is an activin receptor type 2A ligand drug that this has been designed to rebalance the TGF-beta signalling within the osteo-haematopoietic niche by binding activin A and several other ligands in order to address ineffective haematopoiesis. We have observed, in preclinical and clinical studies, that this novel component can promote the moderation and differentiation across all states of both erythropoiesis and thrombopoiesis. Moreover, it is probably able to provide clinical benefits beyond improving haematopoiesis, including increased bone marrow formation, improved iron homeostasis and cardiac damage.
In this phase II trial, we are addressing this compound in patients with anaemia and lower-risk MDS focusing on efficacy and safety.
What were the primary endpoints and methods used in this study to evaluate the efficacy and safety of elritercept? (1:28)
Regarding the primary objective for the trial, we are going to analyze safety and tolerability of this novel drug in patients with anaemia and MDS. Regarding the secondary endpoints, we are going to address efficacy according to the modified IWG 2006 HI-E criteria, and, of course, focusing on reaching transfusion independency, as well as several other exploratory analysis.
We included all the patients that received the recommended part two dose of 3.75 mg/kg every month, with the option to increase the dose up to 5.00 mg/kg every month, subcutaneously.
What were the modified IWG 2006 Hematological Improvement-Erythroid (HI-E), transfusion independence (TI), duration of response (DOR), and changes in QoL scores in the modified intent-to-treat-24 population? How did response rates differ among participants with high transfusion burden (HTB)? (2:25)
The results that we have currently now with this phase II clinical trial are showing that the overall response rates in these patients is between 50–60%. Regarding transfusion independency, one-third of the patients reached transfusion independency. It is important to highlight that even patients within the high transfusion burden are going to respond worst to these drugs, and the numbers of responds are quite similar to the overall population. Also, for patients with a non-free sideroblastic phenotype are going to respond as well as patients with free sideroblasts phenotype. And these two populations, high transfusion burden and non-free sideroblast phenotype, are patients that are not going to respond very well to other TGF-beta inhibitors.
Regarding biomarkers of response, we have also identified that those spaces with lower endogenous equal levels below 500 are going to respond even better.
It is interesting to see that the transfusion independency that we have reached with this novel conform is very prolonged over time. And the median duration of this transfusion independency has not been reached at the last follow-up of the study, but it was in April 2024.
Regarding the improvement in quality of life, these results are going to be translated into an improved quality of life according to an improvement in the fatigue scores of the patients that are going to respond. In this way, patients that respond and reach transfusion independency for more than 24 weeks are going to improve quality on life and improve fatigue score as compared to patients that did not respond. Interestingly, this improvement in quality of life occurs very early after treatment, at 4 weeks of treatment, and improves over time; when we have the treatment, the response is ongoing. And it’s interesting to see the comparison with patients with non response to the drug in which quality of life is not improving and decreased over time.
What were the most frequently observed treatment-emergent adverse events (TEAEs) in this trial, and how were they generally characterized in terms of severity? (5:00)
In this population of lower-risk MDS, there are a frequent number of adverse events. The majority in this clinical trial are immunosuppressant, but the majority of them are not related to the drug. The patients refer generally to symptoms related to gastrointestinal symptoms like diarrhoea or nausea, and also patient symptoms related to the anaemia; around 20% of patients develop these types of symptoms. Nevertheless, the majority of these adverse events were mild to moderate, grades 1 or 2, and were reversible or not related to the drug. Regarding severe adverse events, the majority of them were not related to the drug, and we did not find any fatal adverse event related to the drug. No patients progressed to AML or high-risk MDS. Finally, this novel compound is very well tolerated and is safe for patients.
What longer-term data will be provided in the near future, and what further research is planned in this area? (6:22)
We are analyzing, specifically, several factors in order to address better and to identify better the responses. It’s important to address the mutational profile of the patients that are going to respond to the drug or respond better with prolonged responses. I think this is necessary to address the molecular profile, the impact of the molecular profile on response, saturation of this response. We also have to analyze several other aspects of this novel compound in regard to bone formation, myocardial damage and iron overload. It is important to address efficacy in this, and also secondary endpoints, in order to improve the general status of the disease. Finally, in order to address disease progression, we need to know if this novel compound has any impact on disease progression because targeting activin A could be a driver of disease progression. So it’s important to check this progression evolution in this subset of patients, and the impact finally on overall survival.
Interviewer/Editor: Helen Bowden
Cite: Harrison C. Durable clinical benefit with elritercept in lower-risk MDS: KER050-MD-201 trial. touchHAEMATOLOGY. July, XX, 2024.
