REGAL Trial Receives Green Light to Continue Testing Galinpepimut-S in AML

Angelos Stergiou, MD, ScD

The phase 3 REGAL trial (NCT04229979) evaluating galinpepimut-S (GPS) in patients with acute myeloid leukemia (AML) will continue as planned without modifications following a recommendation from the Independent Data Monitoring Committee (IDMC).¹

The IDMC based its recommendation on an initial prespecified risk-benefit assessment of unblinded data from the trial, factoring in safety, efficacy, and futility.

“Following a prespecified review of unblinded data by the IDMC in accordance with its charter, its recommendation to continue the REGAL study as is, and with trial conduct and integrity intact, [this] is outstanding news. As we have previously reported, we have seen, based on a blinded review of the data conducted this fall, that patients live longer than expected which triggered modifications to the statistical analysis plan, in particular to reduce the number of events for the interim and final analyses, which is very encouraging,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, said in a press release.

The REGAL study is a phase 3, open-label registrational trial comparing GPS and best available therapy in patients with AML who have achieved complete remission following second-line salvage therapy.

The primary end point is overall survival (OS). Secondary end points include leukemia-free survival (LFS), overall survival rate, LFS rate, and minimal residual disease.²

To be eligible for enrollment, patients must be at least 18 years of age and have received a diagnosis of AML according to the World Health Organization criteria; be within 3 months of achieving second morphological complete remission with or without platelet recovery for relapsed but not refractory disease according to the International Working Group 2003 criteria; and be transfusion independent.

Additionally, patients’ leukemic blasts must express WT1, and patients must be ineligible for allogeneic stem cell transplant at the time of enrollment and have received the last dose of antileukemic therapy at least 3 months prior to enrollment. Life expectancy should also be greater than 6 months.

On November 14, 2022, SELLAS announced that the following changes to the statistical analysis plan and protocol would be made following consultation with members of the IDMC, expert AML physicians, and recommendations from the company’s biostatistics experts:³

1. The total targeted enrollment in the study will increase from 116 patients to a range of 125 to no more than 140 patients.
2. The targeted number of fatal events for the interim analysis will be reduced to 60 from 80 and is currently expected to occur in late 2023 or early 2024.
3. The targeted number of fatal events for the final analysis will be reduced from 105 to 80 and is currently expected to occur by the end of 2024.
4. Statistical significance would be achieved by an estimated hazard ratio for OS of 0.636, corresponding to an OS of 12.6 months vs 8 months for GPS vs best available therapy, respectively.

The trial was initially designed using certain assumptions regarding OS for the investigational and control arms, which were accounted for in the protocol and statistical analysis plan for the study. A blinded review of pooled preliminary data from both study arms indicated that the median OS in the pooled study population is likely significantly longer, by approximately two-fold, than originally anticipated and upon which the statistical plan was based. As such, the length of the trial is now expected to be longer than planned.

The changes to the statistical plan and protocol were developed using a conservative application of the O’Brien-Fleming statistical theory, which is suitable when regulatory approval is expected to be based predominantly on results from a single clinical trial and when mortality is the primary end point.

The company notified the FDA of these changes when filing an investigational new drug application for GPS.

References

1. SELLAS Life Sciences’ Independent Data Monitoring Committee Recommends Galinpepimut-S REGAL Trial to Continue as Planned. News release. Sellas Life Sciences Group, Inc. December 8, 2022. Accessed December 9, 2022. https://yhoo.it/3VK4xY9 
2. GPS compared with BAT in AML CR2/CR2p. ClinicalTrials.gov. Updated February 17, 2022. https://clinicaltrials.gov/ct2/show/NCT04229979
3. SELLAS Life Sciences announces update on phase 3 REGAL clinical trial evaluating lead asset, galinpepimut-S, in acute myeloid leukemia. News release. Sellas Life Sciences Group, Inc. November 14, 2022. Accessed December 9, 2022. https://bit.ly/3W8x0qt