Monotherapy Shows Promise in ET and MF as Trials Advance Globally

In an interview with Targeted Oncology, Aaron T. Gerds, MD, hematologist-oncologist at Cleveland Clinic, discusses early data from an ongoing clinical trial evaluating a novel monoclonal antibody in essential thrombocythemia (ET) and myelofibrosis (MF). These data suggest promising therapeutic potential, particularly as a monotherapy.

In ET, a clear and sustained reduction in platelet counts was observed through cycle six, meeting a key endpoint in disease management. These reductions were particularly notable in calreticulin-mutated patients, who typically present with significantly elevated platelet levels.

Beyond hematologic responses, some patients demonstrated early molecular responses, with a measurable decline in mutant calreticulin allele burden. This reduction is considered a meaningful surrogate endpoint, as lower driver mutation levels have been associated with improved myelofibrosis-free survival, thrombosis-free survival, and overall survival. Comparisons were made to other therapies such as hydroxyurea—which can cause a temporary dip in allele burden—and interferon, known for sustained molecular responses when treatment is maintained.

The trial remains ongoing and continues to enroll patients in both the ET and MF cohorts. An expansion cohort is planned, and a companion arm focused on myelofibrosis is progressing in parallel. Top-line data from this arm are expected soon. Importantly, both U.S.-based arms are evaluating monotherapy, while an ex-U.S. trial is investigating combination therapy with ruxolitinib in MF patients. This global effort is expected to offer a comprehensive view of the safety and efficacy profile of the agent.

To date, no significant toxicity signals have emerged, and dosing appears appropriate. As data mature, a combination approach—adding the monoclonal antibody to a JAK inhibitor—could be rationalized, potentially leading to a phase 3 trial in myelofibrosis. For now, monotherapy shows encouraging signs of durable efficacy and a favorable safety profile.

REFERENCE:

Psaila B, Pandey V, Wang LC, et al. INCA035784, a novel, equipotent t cell-redirecting antibody for patients with myeloproliferative neoplasms carrying different types of calreticulin mutations. Presented at: 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract S212.