Phase 3 REGAL Trial of Galinpepimut-S in AML Advances Toward Completion

3D rendering of acute myeloid leukemia (AML) cells

The Independent Data Monitoring Committee (IDMC) has successfully completed the prespecified interim analysis of the phase 3 REGAL trial (NCT04229979) of galinpepimut-S (GPS) for the treatment of patients with acute myeloid leukemia (AML). This analysis, triggered by 60 events (deaths) within the study population, has led to the IDMC recommending that the trial proceed without modifications.¹

The interim analysis assessed the trial’s futility, efficacy, and safety, providing critical insights into GPS’s potential for AML treatment. The IDMC reviewed unblinded data and concluded that GPS exceeded the predetermined futility criteria, with no safety concerns identified.

After a median follow-up of 13.5 months (range 1 month to more than 3 years), fewer than 50% of enrolled patients were confirmed deceased, with a median overall survival (OS) of over 13.5 months. This outcome compares favorably to the historical median OS of approximately 6 months for patients with AML receiving conventional therapies, as seen in prior phase 2 studies.

Additionally, 80% of randomly selected patients treated with GPS in the REGAL study exhibited a specific T-cell immune response, surpassing results from the earlier phase 2 study where the median OS among patients treated with GPS was 21 months vs 5.4 months for patients receiving standard of care therapy, with a GPS-specific immune response of 64%.

“I am thrilled by the positive outcome of the interim analysis of our phase 3 REGAL trial, marking the successful achievement of the most significant milestone for our GPS program to date. The IDMC’s recommendation to support the continued advancement of GPS in our REGAL trial brings us one step closer towards potential approval for the treatment of AML,” said Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, in a press release. “Based on all available data, we believe that GPS could become a transformative treatment option for AML, offering hope to patients with limited choices, especially those with relapsed or refractory disease.”

Based on this evaluation, the IDMC’s recommendation for continuation underscores GPS’s promising preliminary signals of efficacy. The trial now progresses toward its final analysis, which will occur after 80 events (deaths) have been reached. The company anticipates this to be achieved later this year.

“We are optimistic about the IDMC’s recommendation to continue the study without modifications, and diligently preparing for the biologics license application. Importantly, the REGAL trial provides a clear and straightforward path toward seeking regulatory approval for patients with AML in their second complete remission [CR]. We look forward to completing the trial with the final analysis to be conducted once 80 events are reached,” added Stergiou.

“The interim results represent a major step forward in the treatment of AML, offering hope for patients in remission,” said Yair Levy, MD, director of hematologic malignancies research at Texas Oncology Baylor University Medical Center, in the press release. “I am very hopeful that we will see a new standard of care in treating AML patients based on the outcomes we have observed in previous GPS trials.”

About Galinpepimut-S and the REGAL Trial

GPS is a novel immunotherapeutic targeting WT1, a protein overexpressed in various cancers, including AML. The agent mechanism works to stimulate a robust T-cell-mediated immune response.¹ In October 2024, the FDA granted a rare pediatric disease designation to GPS for the treatment of pediatric patients with AML.

The phase 3, open-label, registrational REGAL trial is evaluating GPS for the treatment of patients with AML who have achieved CR following second-line salvage therapy.² Patients will be randomly assigned 1:1 to receive GPS or best available treatment (BAT), stratified by whether they are in second CR (CR2) or CR with incomplete platelet recovery, their cytogenetic risk at diagnosis, whether they harbor minimal residual disease (MRD), and the duration of first CR (CR1) of less than 1 year or 1 year or more.

Patients on the BAT arm may be treated with observation, hypomethylating agents, venetoclax (Venclexta), and/or low-dose ara-C. Patients maintaining remission in CR2 with molecularly targeted agents as determined by the investigator are ineligible. The study has no restrictions on prior use of any agents in the CR1 setting, and GPS cannot be used as adjunct therapy with other agents.

In the GPS arm, patients will receive 70 μg of sargramostim (GM-CSF) on day -2 and day 1 before each GPS injection. The first 2 doses of GM-CSF will be at the same site as GPS. GPS will be given as an immunization induction every 2 weeks for 6 doses on weeks 0 through 10, followed by 4 weeks without treatment. Treatment will resume with 6 booster doses every 4 weeks, starting at week 14 and going through week 34, then a 6-week break. A second booster phase will follow with 3 doses every 6 weeks at weeks 40 through 52. After each dose, patients will be monitored for 30 minutes.

An end of treatment visit will occur 30 days after the last GPS dose, followed by long-term follow-up for leukemia recurrence and OS. Further, all enrolled patients will undergo bone marrow aspirates and biopsies at screening at week 12 and at the end of treatment. As indicated, bone marrow examinations will then be repeated. Patients will also be assessed for safety at each clinic encounter.

OS serves as the primary end point of the study. Secondary end points include leukemia-free survival (LFS), OS rate, LFS rate, and MRD.

REFERENCES

1. SELLAS Life Sciences announces positive outcome of interim analysis for its pivotal phase 3 REGAL trial of GPS in acute myeloid leukemia. News release. SELLAS Life Sciences Group, Inc. January 23, 2025. Accessed January 23, 2025. https://tinyurl.com/2n7kz8wb

2. Galinpepimut-S versus investigator's choice of best available therapy for maintenance in AML CR2/​CRp2 (REGAL). ClinicalTrials.gov. Updated April 9, 2024. Accessed January 23, 2025. https://clinicaltrials.gov/study/NCT04229979?tab=table