4541 - Inducible T cell Costimulatory (ICOS) Receptor Agonist, GSK3359609 (GSK609) alone and in combination with Pembrolizumab (pembro): preliminary results from INDUCE-1 expansion cohorts (EC) in Head and Neck Squamous Cell Carcinoma (HNSCC)

Background

INDUCE-1 is a first in human study investigating GSK609 alone (mono) and in combination (combo) with other regimens including pembro. The study consists of dose escalation (DE) and expansion phases. Findings from DE and the PK/PD mono cohort demonstrated that a range of GSK609 doses (≥0.1-1 mg/kg) have biological and clinical activity supporting the mechanism of action of a non-T cell depleting IgG4 ICOS agonist antibody as a clinical target.

Methods

Eligible patients (pts) for the HNSCC EC had recurrent or metastatic disease, ≤5 prior lines of therapy, measurable disease, and no active autoimmune disease. Pts received 1 mg/kg GSK609 in the mono EC and 0.3 mg/kg GSK609 + 200 mg pembro in the combo EC until disease progression or unacceptable toxicity, up to 2 years (yrs). Disease assessments were performed every 9 weeks (wks) through wk 54 then every 12 wks. Overall response rate (ORR) was assessed for futility in ≥ 10 pts/EC, analyzed by prior PD-1/L1 treatment status (naïve vs. experienced). PD-L1 expression was determined by the 22C3 pharmDx assay.

Results

As of 16 April 2019, 12 of 17 PD-1/L1 experienced pts in the mono and 29 of 34 PD-1/L1 naïve pts in the combo HNSCC ECs had at least 1 disease assessment (evaluable population). In the mono EC, median age was 56 yrs (range: 27-73); 88% were male; 82% received ≥1 prior lines in the metastatic setting. In the combo EC, median age was 61 yrs (range: 33-77); 85% were male; 68% received ≥1 prior lines in the metastatic setting. ORR was 8% (95% CI: 0.2%, 38.5%) and 28% (95% CI: 12.7%, 47.2%) in mono (1 of 8 pts) and combo (8 of 29 pts) ECs, respectively. Median PFS in the combo EC was 5.6 months (95% CI: 2.4, NR). Treatment-related adverse events occurring in the overall mono (n = 208) and combo populations (n = 178) were consistent with that previously reported (Hansen, et al. ESMO, 2018). PD-L1 IHC testing is ongoing.

Conclusions

Preliminary data demonstrate GSK609 has single agent activity in PD-1/L1 experienced HNSCC. The combo of GSK609 with pembro shows promising antitumor activity and a manageable safety profile in pts with previously treated, PD-1/L1 naive HNSCC.

Clinical trial identification

NCT02723955; March 31, 2016.

Editorial acknowledgement

Legal entity responsible for the study

GlaxoSmithKline.

Funding

GlaxoSmithKline.

Disclosure

D. Rischin: Advisory / Consultancy, Uncompensated: MSD; Research grant / Funding (institution): MSD; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Uncompensated: GSK; Research grant / Funding (institution): GSK; Advisory / Consultancy, Uncompensated: BMS; Research grant / Funding (institution): BMS; Advisory / Consultancy, Uncompensated: Regeneron; Research grant / Funding (institution): Roche. A.M.L. Lim: Travel / Accommodation / Expenses: BMS; Research grant / Funding (self): Department of Health (WA) / Raine Medical Research Foundation Clinician Research Fellowship. J. Martin-Liberal: Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Astellas; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Roche; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Ipsen. V. Moreno: Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Regeneron/Sanofi; Travel / Accommodation / Expenses: BMS; Speaker Bureau / Expert testimony, Presentation: BMS; Speaker Bureau / Expert testimony, Presentation: Nanobiotix; Research grant / Funding (self), Educational Grant: Medscape/Bayer. J.M. Trigo Perez: Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Boehringer; Travel / Accommodation / Expenses: Boehringer. C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: GSK; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix. D.C. Cho: Advisory / Consultancy: PureTech; Advisory / Consultancy: Torque; Advisory / Consultancy: Nektar Therapeutics; Advisory / Consultancy: HUYA Pharmaceuticals. A.R. Hansen: Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: GSK; Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: Medimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer-Ingelheim. M. Maio: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Press Conference: BMS; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Press Conference: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eli Lilly; Honoraria (institution): AstraZeneca; Honoraria (institution): Patients’ fee to the University Hospital of Siena. A. Italiano: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Epizyme; Advisory / Consultancy: ImmuneDesign; Advisory / Consultancy: Eli Lily; Advisory / Consultancy: Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): PharmaMar. J.R. Bauman: Advisory / Consultancy: Pfizer. M. Chisamore: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co. Inc. H. Zhou: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. C. Ellis: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. M. Ballas: Full / Part-time employment: GlaxoSmithKline; Shareholder / Stockholder / Stock options: GlaxoSmithKline. A. Hoos: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxoSmithKline. E. Angevin: Advisory / Consultancy: GSK; Advisory / Consultancy: MSD; Advisory / Consultancy: Medimmune; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: AbbVie; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: MedImmune; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Innate Pharma. All other authors have declared no conflicts of interest.