FDA Grants Orphan Drug Designation to Efineptakin Alfa for Pancreatic Cancer

The long-acting human interleukin-7, efineptakin alfa (NT-17), has received an orphan drug designation (ODD) from the FDA for use as a potential therapeutic option in patients with pancreatic cancer.¹

The safety and efficacy of efineptakin alfa paired with pembrolizumab (Keytruda) is under investigation in patients with advanced solid tumors, including pancreatic cancer, as part of an ongoing phase 1/2 study (NCT04332653).²

Efficacy data from the study showed that in patients with pancreatic ductal adenocarcinoma (PDAC; n = 26), at a median follow-up of 3.53 months, the objective response rate (ORR) by RECIST v1.1 criteria was 3.8%, the disease control rate (DCR) was 30.8%, the median duration of response was 8.7 months, and the median time to response (TTR) was 2.8 months.² By iRECIST v1.1 criteria, the ORR was 7.7%, the DCR was 34.6%, the median DOR was 6.1 months, and the median TTR was 3.4 months. The median progression-free survival (PFS) in this cohort was 6.0 months.

“We are excited that the FDA granted NT-I7 an ODD in the treatment of pancreatic cancer. This decision adds further credibility to our existing evidence that NT-I7 has the potential to bring a much-needed therapy option to people suffering from pancreatic cancer,” Luke Oh, PhD, president of NeoImmuneTech, Inc., stated in a press release.¹ “We look forward to continuing our collaboration with FDA, as we explore the therapeutic benefits of combining NT-I7 with other anticancer treatments such as immunotherapies for patients with pancreatic cancer.”

The study enrolled patients with relapsed or refractory microsatellite stable (MSS) colorectal cancer (CRC; arm IV) and PDAC (arm V) who were naive to checkpoint inhibition (CPI), as well as CPI-exposed patients with relapsed or refractory triple-negative breast cancer (TNBC; arm I), non–small cell lung cancer (NSCLC; arm II), and small cell lung cancer (SCLC; arm III).

The dose-expansion phase of the research utilized Simon’s 2-stage minimax design which sought at least 1 responder in 17 evaluable patients in stage I for expansion. For stage II, investigators planned to enroll 8 additional evaluable patients. Participants received efineptakin alfa at 1200 µg/kg intramuscularly every 6 weeks plus 200 mg of pembrolizumab intravenously every 3 weeks until disease progression or intolerable toxicity.

The primary objectives were to examine the preliminary antitumor activity of the regimen in the form of ORRs by RECIST and iRECIST v1.1 criteria. Secondary objectives comprised evaluating DOR, DCR, PFS, and overall survival by RECIST and iRECIST criteria. Investigators are also examining the immunogenicity of the doublet in these populations.

As of the data cutoff date of April 15, 2022, a total of 106 patients were enrolled and 81 were determined to be evaluable for safety and efficacy. To be evaluable for efficacy, they must have had at least 1 post–baseline scan result.

In all patients, the median age was 60.9 years (range, 29-83). Slightly more than half (55.7%) of patients were male, 77.4% had an ECOG performance status of 1, 89.4% received 2 or more prior lines of therapy, 52.8% had stage IV disease at the time of diagnosis, and 56.6% had liver metastasis. In the PDAC cohort specifically, the median age was 66.0 years (range, 31-81), half of patients were male, 68.8% had an ECOG performance status of 1, 90.6% received 2 or more prior lines of therapy, 43.8% had stage IV disease at diagnosis, and 78.1% had liver metastasis.

Additional efficacy data showed that at a median follow-up of 5.13 months, in all patients, the ORR by RECIST v1.1 criteria was 4.9%, the DCR was 32.1%, the median DOR was 4.4 months, and the median TTR was 2.8 months. By iRECIST v1.1 criteria, the ORR was 9.9%, the DCR was 43.2%, the median DOR was 4.4 months, and the median TTR was 3.3 months.

In the TNBC cohort, at a median follow-up of 6.08 months, no patients responded to treatment. By RECIST v1.1 criteria, the DCR was 14.3%; by iRECIST v1.1 criteria, the DCR was 28.6%. The median PFS was 5.1 months. At a median follow-up of 4.85 months in the NSCLC cohort, the ORR by RECIST v1.1 criteria was 5.6%, the DCR was 33.3%, the median DOR was 1.3 months, and the median TTR was 3.6 months; by iRECIST v1.1 criteria, the ORR was 11.1%, the DCR was 66.7%, the median DOR was 3.1 months, and the median TTR was 3.3 months. The median PFS was 6.0 months.

Moreover, in the SCLC cohort, at a median follow-up of 6.08 months, the ORR by RECIST v1.1 criteria was 33.3%, the DCR was 33.3%, the median DOR was 4.1 months, and the median TTR was 1.2 months; these measures were the same according to iRECIST v1.1 criteria. The median PFS was 9.6 months. In the MSS CRC cohort, at a median follow-up of 5.13 months, the ORR by RECIST v1.1 criteria was 3.7%, the DCR was 37.0%, the median DOR was 4.6 months, and the median TTR was 2.8 months; by iRECIST v1.1 criteria, the ORR was 11.1%, the DCR was 40.7%, the median DOR was 4.6 months, and the median TTR was 4.1 months. The median PFS was 6.7 months.

Regarding safety, adverse drug reactions (ADRs) occurred in 74.5% of all patients. When broken down by cohort, they were experienced by 60.0% of those with TNBC, 82.1% of those with NSCLC, 42.9% of those with SCLC, 79.3% of those with MSS CRC, and 75.0% of those with PDAC. In the PDAC cohort, ADRs related to NT-17 were grade 1 (31.3%), grade 2 (28.1%), grade 3 (12.5%), and grade 4 (3.1%). The most common ADRs experienced in that cohort included fever (28.1%), injection site reaction (21.9%), fatigue (15.6%), maculopapular rash (6.3%), and nausea (3.1%).

The investigative agent has also been examined in other phase 1 and 2 trials and showcased the potential to increase T cells across subsets, boost the immune system, and strengthen responses in patients with pancreatic cancer and other solid tumors.¹

References

1. FDA grants orphan drug designation (ODD) status to NeoImmuneTech’s NT-17 for advanced pancreatic cancer treatment. News release. NeoImmuneTech, Inc. January 30, 2024. Accessed February 2, 2024. https://neoimmunetech.com/news/page01_view.html?number=274
2. Naing A, Mamdani H, Barve MA, et al. Efficacy and safety of NT-17, long-acting interleukin-7 plus pembrolizumab in patients with advanced solid tumors: results from the phase 2a study. J Clin Oncol. 2022;40(suppl 16):2514. doi:10.1200/JCO.2022.40.16_suppl.2514