An independent data monitoring committee has recommended that the phase 3 REGAL trial evaluating galinpepimut-S in patients with acute myeloid leukemia should continue without modifications.
An independent data monitoring committee (IDMC) has recommended that the phase 3 REGAL trial (NCT04229979) evaluating galinpepimut-S in patients with acute myeloid leukemia (AML) should continue without modifications.1
The recommendation follows a routine, prespecified risk-benefit assessment of unblinded data collected from the study. Although event driven per protocol, the interim analysis is expected to occur later this year or early next year based on SELLAS Life Sciences Group, Inc.’s statistical assumptions. Additionally, enrollment is anticipated to be completed in fourth quarter of this year, with the IDMC scheduled to meet again in that window.
“At its most recent meeting, we are pleased that the IDMC positively commented on the high level of study integrity and conduct, as well as the rate of enrollment to date,” Angelos Stergiou, MD, ScDhc, president and chief executive officer of SELLAS, stated in a press release. “We look forward to the anticipated completion of enrollment in Q4, as well as the subsequent interim analysis, both significant milestones for our galinpepimut-S development program.”
The REGAL study is enrolling patients with AL who experienced complete remission after second-line salvage therapy; this was defined as having less than 5% myeloblasts in the bone marrow, absence of Auer rods and circulating peripheral blasts, an absolute neutrophil count of greater than 1000 cells/µL and a platelet count of more than 20,000 in the peripheral blood, and the absence of extramedullary disease.2
Patients also needed to have greater than 300 lymphocytes/µL, an ECOG performance status ranging from 0 to 3, and a life expectancy of longer than 6 months. Patients could not be eligible for allogeneic stem cell transplant due to intercurrent medical conditions, patient preference, or lack of an available donor.
Study participants are being randomly assigned to galinpepimut-S or best available therapy (BAT), which could include observation with palliative hydroxyurea (Hydrea) is allowed, decitabine or azacitidine (Vidaza), and/or venetoclax (Venclexta), and/or low-dose ara-C.
Those receiving galinpepimut-S will receive the drug for no more than 15 injections. The first 6 injections are given once every 2 weeks for weeks 0 through 10, and then a treatment-free period of 4 weeks. The next 6 injections (7-12) are given once every 4 weeks, followed by a treatment-free period of 6 weeks. The final 3 injections are administered once every 6 weeks between weeks 40 and 52.
Overall survival (OS) represents the primary end point of the trial, and important secondary end points include leukemia-free survival (LFS) up to 156 weeks; 6-, 9-, and 12-month OS and LFS rates; and minimal residual disease up to 91 weeks.
In November 2022, a consultation with the IDMC, AML experts, and the company’s biostatistics experts resulted in several study modifications.3
First, the total target enrollment increased from 116 patients to 125 to 140 patients. The number of fatal events needed for the interim analysis dropped from 80 to 60, which is expected to happen by late 2023 or early 2024. The number of fatal events needed for the final analysis also dropped, from 105 to 80, and this is expected to occur by the end of 2024. Last, statistical significance would be achieved by an estimated hazard ratio for OS of 0.636, which correlates to 12.6 months with galinpepimut-S compared with 8 months with BAT.3
In December 2022, the IDMC recommended that REGAL continue as planned with the aforementioned modifications.4 That recommendation was based on an initial prespecified risk-benefit assessment of unblinded data from the trial, which considered safety, efficacy, and futility. More recently, in April 2023, the IDMC met again, and came to the same conclusion to continue with the trial.5 They also endorsed all initiatives of REGAL, including the addition of clinical sites in China.