On September 30, 2019 GlaxoSmithKline plc (LSE / NYSE: GSK ) reported that the drug GSK3359609, an agonist antibody to inducible T-cell costimulators designed to selectively increase the function of T cells showed a promising antitumor activity in combination with pembrolizumab in patients with squamous cell carcinoma of the head and neck (HNSCC) without prior anti-PD-1 / L1 treatment (Press release, GlaxoSmithKline, SEP 30, 2019, View Source;811996364.html [SID1234539957]). The results of the INDUCE-1 study also suggested that GSK3359609 has activity as a single agent in patients with HNSCC with a history of anti-PD-1 / L1 treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The safety and tolerance profile of GSK3359609 was consistent with the results reported in the dose increase phase of the INDUCE-1 study. The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona , Spain.

Dr. Axel Hoos, Senior Vice President and Director of R&D in Oncology, commented: "Immunotherapies such as GSK3359609 are a crucial part of our line of cancer products, and we are encouraged by the data from the INDUCE-1 study that demonstrate the potential of this agent to improve Antitumor activity beyond what PD-1 blockade has demonstrated individually The clinical responses observed are encouraging, and based on the precedent with CTLA-4 or PD-1, we aim to demonstrate that the main effect of our ICOS agonist is an improvement in survival for patients, which requires additional studies.On the basis of these results we are initiating the INDUCE-3 study for initial authorization,in order to investigate the potential survival benefit of GSK3359609 with pembrolizumab as a first line in recurrent or metastatic HNSCC for patients positive for PD-L1 ".

The data presented arise from the expansion phase of INDUCE-1, an open study, first in humans, to investigate the drug GSK3359609 as monotherapy and in combination with other regimens. The patients included in the study had recurrent or metastatic HNSCC, and had received up to five lines of prior treatment in the advanced setting. Patients in the monotherapy cohort had received prior anti-PD-1 / L1 treatment, and were given 1 mg / kg of GSK3359609. Patients in the combined treatment cohort had not received prior anti-PD-1 / L1 treatment, and received 0.3 mg / kg of GSK3359609 and 200 mg of pembrolizumab. Patients were evaluated in both cohorts, until the disease progressed or the occurrence of an unacceptable toxicity, for a maximum of two years.

In the 34 evaluable patients who received the combined therapy, the overall response rate was 24% (n = 8; 95% CI: 11, 58.7). The responses in the combined treatment cohort were long lasting, and all patients with response maintained the benefit for 6 months or more (the median was not reached; 95% CI: 4.2 months, NR); The median progression-free survival (SSP) was 5.6 months (95% CI: 2.4, 7.4). Of the 21 patients with known PD-L1 expression data, the majority of patients with response and patients with stable disease had a PD-L1 score below 20. Of the 16 evaluable patients who received monotherapy, the rate of Overall response was 6% (n = 1; 95% CI: 0.2, 30.2).

The INDUCE-1 study was conducted in accordance with an agreement between GSK and Merck & Co, Inc., Kenilworth, NJ , USA. UU. (known as MSD outside the United States and Canada). GSK continues its relationship with MSD to support the combined phase II / III INDUCE-3 clinical study, which will begin in late 2019.

HNSCC is a cancer that develops from squamous cells in the mucous membranes of the mouth, nose and throat, and is the seventh cancer in terms of frequency worldwide, with approximately 600,000 new cases diagnosed each year. i Although HNSCC appears more frequently in men in the fifth or sixth decade of life, the incidence is growing among younger individuals. ii HNSCC tumors are highly immunogenic, and have high expression of immune control point modulators, including ICOS and PD-1. iii

GSK3359609 Clinical Development Program
The clinical development program for GSK3359609 seeks to investigate the anti-tumor potential of targeting the ICOS receptor through an agonist antibody alone and in combination with other therapies against immune control points for the treatment of a range of types of tumors

Currently GSK3359609 is not approved for use anywhere in the world.

GSK in oncology
GSK focuses on maximizing patient survival through transformative medications. The GSK product line focuses on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational drugs that use modalities such as small molecules, antibodies, cells and antibody-drug conjugates, either alone or in combination.