FDA Green Lights ODD for Elraglusib in Pancreatic Cancer

The FDA has granted an orphan drug designation (ODD) for elraglusib (9-ING-41) for treatment of patients with pancreatic cancer, according to Actuate Therapeutics, Inc.¹

Data from a phase 2 study (NCT03678883) investigating the combination of elraglusib with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer support this ODD as treatment with elraglusib generated encouraging clinical activity.²

Among the 21 patients in the study evaluable for response, the disease control rate (DCR) was 62% and the overall response rate (ORR) was 43%, respectively, with 2 confirmed complete responses, 6 confirmed and 1 unconfirmed partial response, 4 patients with stable disease, and 8 with disease progression. However, adverse events (AEs) related to chemotherapy were significant.

“Based on the promising final data from our completed single arm phase 2 study, we have initiated an open label, randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel for the frontline treatment of patients with metastatic pancreatic cancer” said Andrew Mazar, MD, Actuate’s chief operating officer, in a press release.¹

Pancreatic cancer anatomy concept , malignant tumor of pancreas © Лилия Захарчук [stock.adobe.com]

Elraglusib is a small molecule GSK-3β inhibitor currently under investigation for the treatment of adults and children with advanced refractory cancers.

In a phase 1/2 study (NCT03678883), investigators are evaluating the combination of elraglusib with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. The first 2 parts of the trial have been completed with part 1 evaluating elraglusib as a monotherapy and part 2 assessing elraglusib with standard anticancer agents.

Participation in each portion of the study is open to patients with an ECOG performance status of 0-2, no prior therapy in the metastatic setting, and no systemic therapy in the prior 6 months. Patients must also have adequate bone marrow function, liver function, renal function, and blood coagulation.³

The primary end point of the study is DCR with secondary end points of safety and ORR.

A total of 42 patients were enrolled in the study with a median age of 67. Twenty-four patients were females, 18 were males, 38 patients had metastatic disease, and 4 had locally advanced disease.²

Regarding safety, while there were no serious AEs attributed to elraglusib observed to date, AEs attributed to elraglusib included visual disturbance (75%) and infusion reactions (28%). Chemotherapy-related AEs seen in the study deemed grade 1 or 2 included anemia (40%), neutropenia 2 (6%), thrombocytopenia (28%), diarrhea (25%), fatigue (28%), nausea/vomiting (75%), and constipation (28%).

Grade 3 or 4 chemotherapy-related AEs observed among patients included anemia (3%) neutropenia (40%), thrombocytopenia (6%), diarrhea (13%), fatigue (9%), nausea/vomiting (3%), and febrile neutropenia (16%).

Additionally, the median duration of response has not yet been reached.

The study is now in its third part in which investigators are evaluating treatment with elraglusib in combination with gemcitabine and nab-paclitaxel vs gemcitabine and nab-paclitaxel alone for patients with previously untreated metastatic or locally advanced pancreatic cancer.

In addition to this study, 2 other trials are evaluating elraglusib in combination with a checkpoint inhibitor (NCT05239182), and in combination with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX).¹

“Additional investigator-led phase 2 studies for the front line treatment of patients with advanced pancreatic cancer in combination with a checkpoint inhibitor and in patients with metastatic pancreatic cancer in combination with FOLFIRINOX are also in progress, emphasizing our commitment to developing elraglusib for the pancreatic cancer population,” added Mazar, in the press release.

REFERENCES:

1. Actuate Therapeutics receives FDA orphan drug designation for elraglusib for the treatment of pancreatic cancer. News release. Actuate Therapeutics, Inc. August 1, 2023. Accessed August 2, 2023. https://tinyurl.com/2p8jza4y

2. Mahalingam D, Carneiro BA, Safran H, et al. Phase 2 study of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, with gemcitabine/nab-paclitaxel (GnP) in first-line advanced pancreatic ductal adenocarcinoma (PDAC). J Clin Oncol. 2022;40(suppl 578):578-578. doi:10.1200/JCO.2022.40.4_suppl.578

3. 9-ING-41 in patients with advanced cancers. ClinicalTrials.gov. Updated July 19, 2023. Accessed August 2, 2023. https://clinicaltrials.gov/study/NCT03678883