Novel BTK Inhibitor DTRMWXHS-12 Plus Everolimus and Pomalidomide for Hematologic Malignancies

Results from a Phase 1 Trial

According to findings from a phase 1 study recently published in the American Journal of Hematology, DTRMWXHS-12, a novel Bruton’s tyrosine kinase (BTK) inhibitor, combined with everolimus and pomalidomide yielded safe and effective results among patients with relapsed/refractory (R/R) hematologic malignancies such as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. 

Dr Scott Huntington, MD, Yale University, New Haven, Connecticut, and coauthors aimed to assess a primary endpoint of determining the recommended phase 2 dose of this treatment regimen. Secondary endpoints were the safety and tolerability of this combination, as well as its efficacy through overall response rate, progression-free survival, and duration of response. 

32 patients with a median age of 70 years who had R/R CLL, B-cell NHL, or Hodgkin lymphoma were enrolled in this multicenter phase 1 study. All patients received DTRMWXHS-12, followed by doublet therapy (DTRMWXHS-12 plus everolimus), then followed by triplet therapy (DTRMWXHS-12 and everolimus plus pomalidomide) once daily on days 1 to 21 of each 28-day cycle. 

Although no maximum tolerated dose was determined for monotherapy or doublet therapy, the maximum tolerated dose of triplet therapy was DTRMWXHS-12 at 200 mg, everolimus at 5 mg, and pomalidomide at 2 mg. 41.9% of patients (n=13) were highly responsive to treatment, denoting that it had high efficacy in treating patients with R/R hematologic malignancies. 

As endpoints were met, Dr Huntington and coauthors concluded, “Combining DTRMWXHS-12 with everolimus and pomalidomide is tolerable and shows clinical activity.” 

They added, “additional trials could confirm benefit of this all-oral combination therapy for relapsed/refractory lymphomas.” 

Source: 

Huntington SF, Schuster SJ, Ding W, et al. DTRMWXHS ‐12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: An open‐label, multicenter, phase 1a/1b study. Amer J of Hem. Published online March 7, 2023. doi:https://doi.org/10.1002/ajh.26888