Maintenance Galinpepimut-S Appears Effective and Safe in AML in Second CR

Galinpepimut-S (GPS) demonstrated early efficacy signals in patients with acute myeloid leukemia (AML) in second complete remission (CR2) or later in the phase 3 REGAL trial (NCT04229979), which successfully passed its prespecified interim futility, efficacy, and safety analysis.1 Following this analysis, which was triggered by 60 events (deaths) in the study population, the independent data monitoring committee (IDMC) has recommended the trial’s continuation without modifications to the original protocol.

At a median follow-up of approximately 13.5 months (range, 1 month to > 3 years) and approximately 10 months after enrollment completion, fewer than 50% of patients enrolled in REGAL have died. The estimated pooled median overall survival (OS) exceeds 12 months and is longer than the estimated median OS of approximately 6 months for patients with AML in CR2 who did not receive transplant after the second remission.

Furthermore, the GPS-specific immune response rate was 80% in a blinded analysis assessing early immune response in a randomly selected sample of patients being treated with GPS.

“The interim results represent a major step forward in the treatment of [patients with] AML, offering hope for patients in remission,” M. Yair Levy, MD, director of Hematologic Malignancies Research at Texas Oncology Baylor University Medical Center in Dallas, stated in a news release. “I am very hopeful that we will see a new standard of care [SOC] in treating [patients with] AML based on the outcomes we have observed in previous GPS trials.”

In a phase 2 trial investigating GPS in patients with AML in CR2, at a median follow-up of 30.8 months, the median OS in the GPS arm was 21.0 months compared with 5.4 months in patients who received SOC therapy (P < .02).2

REGAL Trial Design

The open-label, registrational REGAL trial enrolled patients at least 18 years of age with AML who had reached second morphological CR with platelet recovery (CR2) or without platelet recovery (CRp2) following second-line salvage therapy.3 Patients needed to have more than 300 lymphocytes/μL, an ECOG performance status of 0 to 3, an estimated life expectancy of longer than 6 months, and adequate hepatic function. Eligible patients could not have been candidates for allogeneic stem cell transplant at the time of study entry and must have received their last dose of re-induction antileukemic therapy at least 4 weeks or 10 half-lives of induction therapy (whichever is shorter) prior to receiving study treatment. Patients must have consented to study treatment within 6 months of having achieved a CR2/CRp2 or later CR.

Patients were randomly assigned to receive GPS or investigator’s choice of best available therapy (azacitidine [Vidaza], venetoclax [Venclexta], decitabine, cytarabine, or observation). Patients in the GPS arm received up to 15 total GPS injections. GPS was admixed with Montanide adjuvant before being administered as a subcutaneous injection. Patients in the GPS arm received granulocyte-macrophage colony-stimulating factor 1 day prior to and on the same day as the GPS/Montanide injection.

OS serves as the primary end point. Secondary end points include leukemia-free survival (LFS), OS rate, LFS rate, and minimal residual disease.

In a SELLAS webinar that aired on January 8, 2025, Levy explained that “in addition to efficacy, [GPS] is also an extremely well-tolerated therapy. GPS efficacy does not come at the cost of quality of life. GPS has been shown to be very safe, with minimal [adverse] effects.”1

Next Steps

The next analysis of REGAL will be conducted when 80 events (deaths) are reached, which SELLAS anticipates will happen in 2025, according to a news release.

“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 1 step closer towards potential approval for the treatment of [patients with] AML,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, stated in the news 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. 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 [GPS for] patients with AML in their second complete remission. We look forward to completing the trial.”

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://www.globenewswire.com/news-release/2025/01/23/3014244/0/en/SELLAS-Life-Sciences-Announces-Positive-Outcome-of-Interim-Analysis-for-its-Pivotal-Phase-3-REGAL-Trial-of-GPS-in-Acute-Myeloid-Leukemia.html
2. SELLAS announces positive follow-up phase 1/2 clinical data for galinpepimut-S (GPS) in acute myeloid leukemia (AML). News release. SELLAS Life Sciences Group, Inc. February 26, 2020. Accessed January 23, 2025. https://ir.sellaslifesciences.com/news/News-Details/2020/SELLAS-Announces-Positive-Follow-Up-Phase-12-Clinical-Data-for-Galinpepimut-S-GPS-in-Acute-Myeloid-Leukemia-AML/default.aspx
3. 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