- Ruth Plummer (Newcastle-upon-Tyne, Tyne and Wear, United Kingdom)
1O - Inducible T cell co-stimulatory (ICOS) receptor agonist, GSK3359609 (GSK609) alone and combination with pembrolizumab: Preliminary results from INDUCE-1 expansion cohorts in head and neck squamous cell carcinoma (HNSCC) (ID 219)
- Christophe Le Tourneau (Paris, France)
- Christophe Le Tourneau (Paris, France)
- Danny Rischin (Melbourne, VIC, Australia)
- Stefanie Groenland (Amsterdam, Netherlands)
- Annette Lim (Nedlands, WA, Australia)
- Juan Martin-Liberal (Barcelona, Spain)
- Victor Moreno (Madrid, Spain)
- Jose Manuel Trigo (Málaga, Spain)
- Matthen Mathew (New York, NY, United States of America)
- Daniel Cho (New York, NY, United States of America)
- Aaron Hansen (Toronto, AB, Canada)
- David Vincente Baz (Sevilla, Spain)
- Michele Maio (Siena, Italy)
- Antoine Italiano (Bordeaux, France)
- Jessica Bauman (Philadelphia, PA, United States of America)
- Michael Chisamore (North Wales, PA, United States of America)
- Helen Zhou (Collegeville, PA, United States of America)
- Catherine Ellis (Collegeville, PA, United States of America)
- Marc Ballas (Collegeville, PA, United States of America)
- Axel Hoos (Collegeville, PA, United States of America)
- Eric Angevin (Villejuif, CEDEX, France)
Abstract
Background
INDUCE-1 is a first-in-human study investigating GSK609 alone (mono) and in combination (combo) with other regimens including pembrolizumab (pembro). The study consists of dose escalation (DE) and expansion phases. Findings from DE and PK/PD mono cohorts 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 HNSCC expansion cohorts (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 22C3 pharmDx assay.
Results
As of 16 April 2019, 12/17 PD-1/L1-experienced pts in mono and 29/34 PD-1/L1-naïve pts in combo head and neck squamous cell carcinoma (HNSCC) ECs had at least one disease assessment (evaluable population). In the mono EC, median age was 56 yrs (range: 27-73); 88% were male; 82% received ≥1 prior line in the metastatic setting. In the combo EC, median age was 61 yrs (range: 33-77); 85% were male; 68% received ≥1 prior line in the metastatic setting. ORR was 8% (95% CI: 0.2%, 38.5%) and 28% (95% CI: 12.7%, 47.2%) in mono (1/8 pts) and combo (8/29 pts) ECs, respectively. Median PFS in the combo EC was 5.6 months (95% CI: 2.4, NR). Treatment-related adverse events 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.
Conclusion
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
EudraCT 2016-000148-32; NCT02723955.
Editorial acknowledgement
Victoria Hunter of Fishawack Indicia Ltd, UK.
Legal entity responsible for the study
GlaxoSmithKline (GSK).
Funding
GlaxoSmithKline (GSK) in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
C. Le Tourneau: Advisory/Consultancy: GSK; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Amgen; Advisory/Consultancy: Rakuten; Advisory/Consultancy: Celgene. D. Rischin: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Roche. A. Lim: Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS. J. Martin-Liberal: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Speaker Bureau/Expert testimony: Astellas; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. V. Moreno: Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Regeneron/Sanofi; Speaker Bureau/Expert testimony: Nanobiotix; Research grant/Funding (self): Medscape/Bayer. J.M. Trigo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD. M. Mathew: Shareholder/Stockholder/Stock options: Navinta LLC. D. Cho: Advisory/Consultancy: Nektar Therapeutics; Advisory/Consultancy: PureTech; Advisory/Consultancy: HUYA Pharmaceuticals; Advisory/Consultancy: Torque Pharmaceuticals. A. Hansen: Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Boston Biomedical; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Medimmune. D. Vincente Baz: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MSD. M. Maio: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Incyte; Honoraria (self), Honoraria (institution): Merck; Honoraria (self), Honoraria (institution): Novartis. A. Italiano: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Epizyme; Advisory/Consultancy: ImmuneDesign; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pharmamar. J. Bauman: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bayer. M. Chisamore: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. H. Zhou: Full/Part-time employment: GSK. C. Ellis: Shareholder/Stockholder/Stock options, Full/Part-time employment: GSK. M. Ballas: Shareholder/Stockholder/Stock options, Full/Part-time employment: GSK; Shareholder/Stockholder/Stock options: BMS; Shareholder/Stockholder/Stock options: Abbott; Shareholder/Stockholder/Stock options: Novartis. A. Hoos: Shareholder/Stockholder/Stock options, Full/Part-time employment: GSK. E. Angevin: Advisory/Consultancy: GSK; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene Research; Advisory/Consultancy, Travel/Accommodation/Expenses: MedImmune; Travel/Accommodation/Expenses: AbbVie; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Innate Pharma; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.