Second-line maintenance therapy with the experimental vaccine galinpepimut-S (GPS) significantly prolongs the life of patients with acute myeloid leukemia (AML) who are on their second remission of the disease, according to the final results of a pilot trial, Sellas Life Sciences announced.
The final follow-up of the Phase 1/2 clinical trial showed that GPS extended the median overall survival by 15.6 months, compared to the best available standard treatments. The results further back the potential success of an ongoing Phase 3 study evaluating GPS’ safety and efficacy in AML patients on their second remission.
“We’re extremely pleased with this follow-up data, which show that GPS may have potential as a longer-term therapy for AML patients in CR2 [in second complete remission], an aggressive disease where the majority of patients typically relapse and have a survival rate of approximately 5 months with best standard therapy,” Angelos Stergiou, MD, Sellas’ president and CEO, said in a press release.
“The 21-month survival data observed further increases our confidence in the potential of GPS as a maintenance treatment for AML patients in CR2, the same patient population as our pivotal Phase 3 study, known as REGAL,” Stergiou said.
Galinpepimut-S (also known as WT-1 vaccine) is an investigational immunotherapy vaccine being developed to treat several types of cancer. The vaccine targets Wilm’s Tumor 1 (WT1), one of the most common cancer-associated proteins.
GPS is made up of four protein pieces, two of which are designed to induce a strong innate immune response against WT1, involving CD4+, and CD8+ immune T-cells, that is expected to target and destroy cancer cells. Much like a conventional vaccine, GPS was designed to set in motion an “immunological memory” that enables the immune system to continuously clear residual cancer cells and stop tumors from coming back.
In 2015, Sellas reported initial positive data from the pilot Phase 1/2 study (NCT00665002) evaluating GPS’ safety and immunogenicity (ability to boost the immune system) in AML patients on their second remission (CR2) — patients whose disease came back after a first-line of therapy, and who achieved complete remission (no detectable signs of cancer) after receiving second-line treatment.
Participants received six vaccinations delivered by injections under the skin bi-weekly over 10 weeks; after that period, GPS dosing was continued monthly until patients received 12 vaccinations or their disease returned or worsened.
At a median follow-up of 19.3 months, GPS-treated patients survived nearly 11 months more than those given the best standard therapy (16.3 months vs. 5.4 months). The vaccine was well-tolerated, with no patients leaving the study due to toxicity.
The final analysis now shows that GPS extends patients’ overall survival to 21 months, after a median follow-up of 30.8 months. The vaccine continued to be well-tolerated throughout the entire study.
“These follow-up data build upon the initially published clinical results from the Phase 1/2 study of GPS in AML patients in CR2 and provide further evidence that this novel immunotherapeutic vaccine approach may improve outcomes for patients in this setting, who often harbor measurable residual disease and have a poor prognosis if they are unable to undergo allotransplant,” said Javier Pinilla-Ibarz, MD, PhD, principal investigator of the trial. Pinilla-Ibarz also is the director of Immunotherapy for Malignant Hematology at the Moffitt Cancer Center in. Tampa, Florida.
Building upon these positive results Sella launched the Phase 3 REGAL trial (NCT04229979), which is currently enrolling patients.
This open-label study will recruit about 116 AML patients in complete remission after a second-line treatment, who will be assigned randomly to either maintenance therapy with GPS or the physician’s choice of best available treatment.
Eligible patients must be in full remission of their cancer, and cannot qualify for allogeneic stem-cell transplantation. They may or may not have normal platelet levels at the time of enrollment. More information about the trial, including contacts and locations, can be found here.
REGAL’s main goal is to determine whether GPS, given as maintenance therapy, prolongs the life of patients compared to standard treatments. Secondary measures include time lived without leukemia coming back, anti-tumor immune responses, measures of residual disease, and assessments of tumor microenvironment in bone marrow samples. An interim analysis is expected in the fourth quarter of 2021.
“Given these results, it is particularly exciting to be involved in the ongoing pivotal Phase 3 REGAL study of GPS in AML patients in CR2,” said Hagop M. Kantarjian, MD, REGAL’s principal investigator.
“We are working to rapidly enroll patients who meet entry criteria for this study and believe these compelling results will enhance the visibility of this novel therapy and encourage broader participation in the pivotal Phase 3 trial. I look forward to initial results from the REGAL study, as I remain supportive of GPS’s potential promise as an immunotherapeutic agent in the AML CR2 setting,” said Kantarjian, who also is a professor and chair of the Department of Leukemia at the University of Texas – MD Anderson Cancer Center.