Galinpepimut-S Earns FDA Rare Pediatric Disease Designation for AML

FDA

The FDA has granted rare pediatric disease designation to galinpepimut-S (GPS) for the treatment of pediatric patients with acute myeloid leukemia (AML).¹

GPS is a multivalent, heteroclitic Wilms tumor 1 (WT1) peptide vaccine that has been investigated in a prior phase 2 study (NCT01266083) in adult patients in complete remission (CR) from AML or acute lymphoblastic leukemia (ALL).^1,2 The agent is also being evaluated vs investigator’s choice of best available maintenance therapy in the phase 3 REGAL trial (NCT04229979) in adult patients with AML in second or later CR or second or later CR with incomplete platelet recovery.³

Data from the phase 2 study showed that 86% of patients (n = 22) were evaluable for survival at 3 years, and 47% of these patients (n = 9 of 19) were alive for at least 3 years, surpassing the study’s prespecified 3-year overall survival (OS) rate of 34%.² The median OS from diagnosis was not reached but was expected to exceed 67.6 months. The estimated 6- and 9-month OS rates following vaccination were 100% (95% CI, 100%-100%) and 77% (95% CI, 54%-90%), respectively.

Additionally, from first CR, the median disease-free survival (DFS) was 16.9 months. The median event-free survival (EFS) was 9.4 months; the estimated 6- and 9-month EFS rates were 64% (95% CI, 40%-80%) and 54% (95% CI, 32%-72%), respectively.

“GPS has already demonstrated promise in clinical settings for AML, and we believe its potential could extend to pediatric patients,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS Life Sciences Group, stated in a news release.¹ “Receiving rare pediatric disease designation from the FDA is another acknowledgment of the critical need for new treatment options for AML and our results in adult patients. In our phase 2 trial in adult patients which included patients as young as 25, clinical benefits were significantly higher in younger patients, which was expected based on the mechanism of action of GPS that is mediated via the immune system that is generally better preserved in younger patients, and even more so in children. With both of our development candidates, GPS and SLS009, now granted rare pediatric disease designation for AML, this recognition further reinforces our commitment to delivering potential new therapies to children affected by this challenging condition.”

Notably, findings from a subgroup analysis of the phase 2 trial showed that the median OS and DFS were both not reached (NR) in patients under 60 years of age (n = 9).²

The single-center phase 2 study conducted at Memorial Sloan Kettering Cancer Center in New York, New York, enrolled patients at least 18 years of age with AML or ALL who have completed induction therapy, achieved a first CR, and completed any planned post-remission therapy.⁴ First CR was required within 2 years of completing chemotherapy. WT1-positive disease was required for enrollment, and patients were also required to have a Karnofsky performance status of at least 50% and adequate hematologic, renal, and liver function.

Investigators excluded patients with documented evidence of leptomeningeal disease, those who underwent autologous or allogeneic stem cell transplant, and patients with active infections requiring systemic antimicrobials.

All patients received GPS as 6 subcutaneous doses administered once every 2 weeks over a 10-week period. Patients also received 70 μg of granulocyte-macrophage colony stimulating factor to pre-stimulate injection sites.²

Safety and 3-year OS rate in patients with AML served as the trial’s primary end points. Secondary end points included DFS, immunologic responses, minimal residual disease assessments, and OS.⁴

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 95.5% of patients. The most common TRAEs were mild to moderate local reactions and inflammation, including injection site reaction (45.5%), fatigue (31.8%), skin induration (31.8%), and pruritus (27.3%). Study authors explained that these TRAEs were self-limited and responded to local supportive measures and analgesics.²

References

1. SELLAS announces U.S. FDA rare pediatric disease designation (RPDD) granted to galinpepimut-S (GPS) for the treatment of pediatric acute myeloid leukemia. News release. SELLAS Life Sciences Group. October 15, 2024. Accessed October 15, 2024. https://ir.sellaslifesciences.com/news/News-Details/2024/SELLAS-Announces-U.S.-FDA-Rare-Pediatric-Disease-Designation-RPDD-Granted-to-Galinpepimut-S-GPS-for-the-Treatment-of-Pediatric-Acute-Myeloid-Leukemia/default.aspx
2. Maslak PG, Dao T, Bernal Y, et al. Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv. 2018;2(3):224-234. doi:10.1182/bloodadvances.2017014175
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 October 15, 2024. https://clinicaltrials.gov/study/NCT04229979
4. WT-1 analog peptide vaccine in acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). ClinicalTrials.gov. Updated November 30, 2018. Accessed October 15, 2024. https://clinicaltrials.gov/study/NCT01266083