GSK Halts Two Mid-Stage Trials of ICOS Agonist Feladilimab Following Futility Findings

Compiled by river

On April 14, according to foreign media reports, GSK announced its decision to cancel two interim trials of feladilimab (GSK3359609). Feladilimab is an inducible T-cell co-stimulator (ICOS) agonist antibody that plays a crucial role in the proliferation, survival, and recognition of foreign antigens by T cells. It can activate the ICOS receptor without causing cell exhaustion, potentially helping to further enhance the immune response of T cells and improve the efficacy of immune checkpoint inhibitors.

Based on the recommendation of the Independent Data Monitoring Committee, GSK has terminated treatment in the INDUCE-3 trial, a randomized, double-blind, adaptive study evaluating the combination with Keytruda for advanced or metastatic head and neck squamous cell carcinoma. Additionally, GSK has decided to halt the INDUCE-4 Phase II clinical trial, which is also a study investigating feladilimab in combination with Keytruda and chemotherapy.

In the previously reported INDUCE-1 study, feladilimab in combination with the PD-1 cancer immunotherapy pembrolizumab demonstrated highly promising antitumor activity in patients with head and neck squamous cell carcinoma (HNSCC) who were naive to prior PD-1/L1 immune checkpoint inhibitor therapy (PD-1/L1-naïve). Among the 34 evaluable patients receiving the combination therapy, the overall response rate (ORR) was 24% (n=8; 95% CI: 11–58.7). Responses were durable, with all responders achieving a duration of response (DOR) ≥6 months (median not reached; 95% CI: 4.2 months–NR). The median progression-free survival (PFS) was 5.6 months (95% CI: 2.4–7.4). Among the 21 patients with available PD-L1 expression data, the majority of responders and patients with stable disease had a PD-L1 score <20.

Furthermore, studies have demonstrated that feladilimab monotherapy exhibits antitumor activity in patients with head and neck squamous cell carcinoma (HNSCC) who have previously received PD-1/L1 immune checkpoint inhibitor therapy (PD-1/L1 pretreated). Among 16 evaluable patients, the overall response rate (ORR) was 6% (n=1; 95% CI: 0.2–30.2).

This setback was not unexpected, as Jounce Therapeutics’ vopratelimab also failed in an interim analysis of a mid-stage trial last autumn. In that study, ipilimumab was used to induce ICOS-hi CD4+ T cells, followed by administration of vopratelimab, with the aim of enhancing the proliferation and expansion of ICOS-hi CD4+ T cells—a mechanism associated with the durable clinical benefits observed with vopratelimab monotherapy or in combination with PD-1 inhibitors in the ICONIC trial. However, early evaluation data from the trial assessing vopratelimab in combination with ipilimumab in patients with non-small cell lung cancer (NSCLC) who had previously received PD-(L)1 therapy indicated that the study did not meet the prespecified interim criteria for continued enrollment.

GSK stated that it would evaluate all data to assess the impact on the overall clinical development program for feladilimab. This does not sound promising. For GSK in 2021, this represents a particularly difficult setback, as CEO Emma Walmsley and Chief Scientific Officer Hal Barron had promised to provide robust evidence this year demonstrating improvement in this pipeline.

References:

1.GlaxoSmithKline scraps two key mid-stage trials for their ICOS drug in the latest setback for the field

2.GSK presents new data showing promising anti-tumour activity with GSK3359609, an ICOS receptor agonist, in combination with pembrolizumab in head and neck squamous cell carcinoma (HNSCC)

3.Three Biotechs Shutter Clinical Programs After Futility Analysis or Failed Trials