Efineptakin Alfa Represents Potentially Effective Option in Kaposi Sarcoma

Efineptakin alfa (NT-I7) demonstrated early signals of efficacy and safety for the treatment of patients with Kaposi sarcoma, according to preliminary findings from the phase 1 CITN-17 study (NCT04893018) published in the Journal for ImmunoTherapy of Cancer.1

Among response-evaluable patients who received efineptakin alfa (n = 7), the objective response rate (ORR) was 42.9% (95% CI, 9.9%-81.6%). Three patients experienced stable disease and 1 patient had progressive disease. Notably, all patients who responded to efineptakin alfa had HIV, and 2 of the 3 responders received dose level 2—960 µg/kg—of the agent. A dose-limiting toxicity (DLT) occurred in 1 patient within the first cycle; this patient came off treatment at week 5 and was not included in the response assessment, which occurred at week 9 prior to the second treatment cycle.

Safety data showed that there were no deaths reported among all patients who received efineptakin alfa (n = 8). The median number of treatments with efineptakin alfa was 3.5 doses, and 4 patients received all 4 doses. The remaining patients discontinued treatment due to a DLT (n = 1), disease progression (n = 1), participant withdrawal (n = 1), or physician decision (n = 1).

“In this study evaluating [efineptakin alfa] in participants with Kaposi sarcoma, doses of efineptakin alfa of 480 µg/kg and 960 µg/kg in 8 participants were associated with grade 1 and 2 treatment-related adverse effects [TRAEs],” Ramya Ramaswami, MBBS, MPH, the Lasker Clinical Research Scholar and a medical oncologist in the HIV and AIDS Malignancy Branch at the National Institutes of Health in Bethesda, Maryland, and coauthors wrote in the publication. “Treatment was safe among patients with HIV with no significant impact on HIV viral load. However, the primary objective was not met due to early study closure following termination of funding. Despite early termination, we noted that among 7 response-evaluable participants, the majority of whom had prior systemic Kaposi sarcoma therapy, [there was] a response in a subset of participants.”

Efineptakin alfa is a long-acting immunoglobulin fusion protein that contains a recombinant form of endogenous human IL-7 fused to a hybrid crystallizable fragment region. Study authors hypothesized that treatment with the agent could cause enhanced T-cell mediated antitumor activity, especially in patients with low levels of circulating T cells.

Examining the Phase 1 Study’s Design

The multicenter CITN-17 study was conducted in the US and enrolled patients with histologically confirmed Kaposi sarcoma who were more than 18 years of age and had an ECOG performance status of less than 2. Patients with any-stage Kaposi sarcoma were allowed to enroll and those with visceral disease also were included if they did not require immediate intervention and had limited tumor-related symptoms. Patients with HIV needed to be on effective antiretroviral therapy for a minimum of 3 months with inadequate regression of Kaposi sarcoma or persistent Kaposi sarcoma which affected their quality of life. These patients were also required to have an undetectable HIV viral load of less than 40 copies/mL.

The study employed a 3+3 design. Patients received efineptakin alfa at a dose of 480 µg/kg, 960 µg/kg, or 1200 µg/kg for 4 doses administered intramuscularly every 9 weeks. The primary end point was to examine the safety of efineptakin alfa over the 3 escalating dose levels and to identify a maximum tolerated dose. Secondary end points included ORR in patients with Kaposi sarcoma and examining the kinetics of CD4- and CD8-positive T cells in the blood.

Kaposi sarcoma response was determined via modified AIDS Clinical Trials Group (ACTG) Kaposi sarcoma criteria at weeks 0, 9, 13, 18, 27, and 36. Safety was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0.

At baseline, the median age of patients was 55 years (range, 33-70) and all were male. Most patients were White (75%), had ACTG stage T0 disease (75%), and were HIV positive (63%). Fifty percent of patients received prior systemic therapy, which was comprised of chemotherapy (50%), immunotherapy (13%), and other treatments (38%); 25% of patients underwent prior radiation therapy and 13% had previous surgery.

Further Safety Data From the Phase 1 Study

Additional safety findings showed that all TRAEs were grade 1 to 2 in severity. The most common any-grade TRAE was local injection site reaction (n = 7), which was managed with antihistamines and topical steroids. Grade 2 local injection site reaction occurred in 1 patient following the first dose, leading the patient to come off treatment 5 weeks after cycle 1; this met the criteria for a DLT and a serious AE. Another patient experienced a serious AE due to a hospitalization resulting from a grade 2 infection and grade 3 chylothorax that was not deemed to be treatment related; this patient also had baseline pleural effusions related to Kaposi sarcoma and discontinued treatment following the hospitalization.

Grade 1 to 2 treatment-emergent AEs (TEAEs) occurred at a rate of 88%. Beyond injection site reaction, common any-grade TEAEs included increased alanine aminotransferase levels (50%), increased lymphocyte count (50%), and increased asparate aminotransferase levels (38%).

“[Efineptakin alfa] administration demonstrated preliminary evidence of activity among patients with HIV in whom CD4-positive T-cell counts are associated with Kaposi sarcoma onset and persistence,” the study authors wrote in conclusion. “With up to 4 intramuscular injections, this treatment may be beneficial in limited-resource settings, such as sub-Saharan Africa, where Kaposi sarcoma is highly prevalent. However, more data are needed to identify an optimal dose of [efineptakin alfa] in this population.”

Reference

1. Ramaswami R, Kask AS, D’Amico L, et al. Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma. J Immunother Cancer. 2025;13(2):e010291. doi:10.1136/jitc-2024-010291