GlaxoSmithKline Discontinues Feladilimab in Clinical Trials for Metastatic HNSCC

GlaxoSmithKline plc has announced that they will stop enrolling patients in the phase 2 INDUCE-3 (NCT04128696) and INDUCE-4 (NCT04428333) trials while simultaneously ending the use of feladilimab, originally GSK3359609, for the treatment of PD-L1-positive recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) after the recommendation of the Independent Data Monitoring Committee, according to a press release by the organization.¹

INDUCE-3 was meant to evaluate the efficacy and safety of pembrolizumab (Keytruda) and feladilimab, an investigation inducible T cell co-stimulatory agonist, for the treatment of PD-L1 positive recurrent or metastatic HNSCC. INDUCE-4 evaluated the same combination in the same cancer types, except with the addition of a platinum-based chemotherapy.

INDUCE-3 was meant to enroll an estimated 600 participants set to end in July 2023. Intended primary outcomes included overall survival (OS) and progression free survival (PFS). Secondary outcomes included milestone OS at 12 and 24 months, overall response rate (ORR), disease control rate (DCR), and duration of response (DoR).

The study was made up of two arms. In arm 1, patients received a combination of feladilimab and pembrolizumab as an infusion once every 3 weeks. In arm 2, patients were meant to receive a placebo and pembrolizumab as an infusion once every 3 weeks.

INDUCE-4 aimed to enroll 640 patients and had OS and PFS as primary endpoints. Secondary endpoints included milestone OS at 12, 24, and 36 months alone with ORR, DCR, and DoR. Averse events (AE) were also meant to be measured.

Two arms of the study were planned. In arm 1, patients were meant to receive a combination of feladilimab, pembrolizumab, and 5-FU platinum chemotherapy. Patients in arm 2 were to receive the same combination, except with a placebo instead of feladilimab.

The safety of feladilimab in combination with a 5-FU platinum chemotherapy with or without pembrolizumab for the treatment of advanced solid tumors was established in the INDUCE-1 trial (NCT02723955). The dose-escalation and expansion study had an estimated enrollment of 873 participants. Primary endpoints included the number of AEs and the number of participants with dose-limiting toxicities. Secondary outcomes included DCR and OS.

The 10 arms of the dose-expansion and escalation study looked at feladilimab as both a monotherapy and in combination with pembrolizumab, chemotherapy, or other agents at different dose amounts.

At an interim analysis found that the combination had a manageable safety profile. Most AEs observed were grade 1 or 2 and consistent with toxicities associated with pembrolizumab and 5-FU platinum chemotherapy. Investigators note in their analysis of the interim results that further follow-up and investigation is warranted in order to determine the long-term safety and efficacy of the combination.²

Additionally, 10 patients were evaluable for confirmed best overall response in all cohorts. Of those 10, 2 had partial response, 6 patients had stable disease, and 2 patients were non-evaluable. No differences were found between feladilimab exposure and feladilimab as a monotherapy.²

Data from INDUCE-3 and INDUCE-4 will be evaluated in order to assess the impact on the overall clinical development of a feladilimab program.¹

_REFERENCE:

_{1.GSK provides update on feladilimab, an investigational inducible T cell co-stimulatory (ICOS) agonist. News Release. April 14, 2021. Accessed April 16, 2021. https://bit.ly/32lr4Aj.}

_{2.Massarelli E, Balmanoukian AS, Vieito M, et al. INDUCE-1: Report on safety run-in cohorts combining Inducible T-cell co-stimulatory receptor (ICOS) agonist GSK3359609 (GSK609) with platinum+5-FU chemotherapy (5-FU/plat), with or without pembrolizumab (PE), for the treatment of advanced solid tumors. J Clin Oncol. 2020; 38 (suppl 15): 6544-6544. doi: 10.1200/JCO.2020.38.}