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12ms
New P1/2 trial • Combination therapy
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Blenrep (belantamab mafodotin-blmf) • GSK3174998
1year
DREAMM 5: Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov)
P1/2, N=464, Recruiting, GlaxoSmithKline | Trial completion date: Feb 2028 --> Feb 2029 | Trial primary completion date: Feb 2025 --> Feb 2026
Trial completion date • Trial primary completion date • Combination therapy
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lenalidomide • Jemperli (dostarlimab-gxly) • dexamethasone • pomalidomide • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
over1year
Combination therapy • Trial completion • Metastases
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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PD-L1 IHC 22C3 pharmDx
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
over1year
First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). (PubMed, J Immunother Cancer)
GSK3174998±pembrolizumab was well tolerated over the dose range tested and demonstrated target engagement. Limited clinical activity does not support further development of GSK3174998±pembrolizumab in advanced cancers.
P1 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • GZMB (Granzyme B) • FOXP3 (Forkhead Box P3)
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Keytruda (pembrolizumab) • GSK3174998
2years
Manufacturing-dependent change in biological activity of the TLR4 agonist GSK1795091 and implications for lipid A analog development. (PubMed, Clin Transl Sci)
A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. Structural characterization revealed GSK1795091 aggregate size in the modified formulation to be twice that in the original formulation, suggesting a negative correlation between GSK1795091 aggregate size and PD activity. This may have important clinical implications for future development of structurally similar compounds.
Journal
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IL10 (Interleukin 10) • TLR4 (Toll Like Receptor 4) • IL1R1 (Interleukin 1 receptor, type I)
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Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
over2years
Trial completion
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CRP (C-reactive protein)
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Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
3years
DREAMM-5 platform trial: Belantamab Mafodotin (GSK2857916; belamaf; BLENREP) in combination with five different novel agents in patients (Pts) with Relapsed/ Refractory Multiple Myeloma (RRMM) (DGHO 2021)
Sub-study 1 (combination with GSK3174998, OX40 agonist Ab) is closed to enrolment. Sub-studies 2 (combination with GSK3359609, feladilimab, ICOS agonist), 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics], gamma-secretase inhibitor), and 4 (combination with dostarlimab, PD-1 antagonist) are open to enrolment...Nirogacestat and isatuximab produced by and used in collaboration with SpringWorks Therapeutics and Sanofi, respectively. Encore Statement: Presented at 26th Congress of the European Hematology Association (Richardson et al, 2021); submitted with permission of original authors.
Clinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker
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PD-1 (Programmed cell death 1) • ICOS (Inducible T Cell Costimulator)
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Jemperli (dostarlimab-gxly) • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
3years
Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1) (clinicaltrials.gov)
P1, N=828, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Jun 2023 | Trial primary completion date: Dec 2024 --> Jun 2023
Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
over3years
Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. (PubMed, Future Oncol)
Belantamab mafodotin (belamaf) is a BCMA-targeted antibody-drug conjugate recently approved as monotherapy for adults with relapsed/refractory multiple myeloma who have received ≥4 prior therapies. Here, we describe the rationale and design of DREAMM-5, an ongoing Phase I/II platform study evaluating the safety and efficacy of belamaf combined with novel agents, including GSK3174998 (OX40 agonist), feladilimab (an ICOS; GSK3359609), nirogacestat (a gamma-secretase inhibitor; PF-03084014) and dostarlimab (a PD-1 blocker) versus belamaf monotherapy for patients with relapsed/refractory multiple myeloma. Clinical trial registration: NCT04126200 (ClinicalTrials.gov).
Journal • Combination therapy
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ICOS (Inducible T Cell Costimulator)
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Jemperli (dostarlimab-gxly) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
4years
[VIRTUAL] Dreamm-5 Platform Trial: Belantamab Mafodotin (Belamaf) in Combination with Four Different Novel Agents in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2020)
Substudies 1 (combination with GSK3174998, OX40 agonist antibody), 2 (combination with GSK3359609, ICOS agonist antibody), and 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics], gamma-secretase inhibitor) are currently open to enrollment. Substudy 4 (combination with dostarlimab; PD-1 antagonist antibody) is under review...Funding: GSK (Study 208887); belamaf drug linker technology licensed from Seattle Genetics; belamaf monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa; nirogacestat gamma-secretase inhibitor produced by and used in collaboration with SpringWorks Therapeutics. Figure: DREAMM-5 study design
Clinical • Combination therapy
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CD38 (CD38 Molecule) • ICOS (Inducible T Cell Costimulator)
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Jemperli (dostarlimab-gxly) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
over4years
Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=54, Active, not recruiting, GlaxoSmithKline | Suspended --> Active, not recruiting | N=162 --> 54
Clinical • Enrollment closed • Enrollment change • Combination therapy
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CRP (C-reactive protein)
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Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
over4years
Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=162, Suspended, GlaxoSmithKline | Trial primary completion date: Dec 2021 --> Aug 2020
Clinical • Trial primary completion date • Combination therapy
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CRP (C-reactive protein)
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Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
over4years
Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1) (clinicaltrials.gov)
P1; Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024
Combination therapy • Trial completion date • Trial primary completion date • Clinical
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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VENTANA PD-L1 (SP263) Assay
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
over4years
[VIRTUAL] DREAMM-5 PLATFORM TRIAL: BELANTAMAB MAFODOTIN IN COMBINATION WITH NOVEL AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) (EHA 2020)
Sub-studies 1 (combination with GSK3174998, OX40 agonist antibody) and 2 (combination with GSK3359609, ICOS agonist antibody) are currently enrolling. Sub-study 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics]) is projected to begin enrollment in the first half of 2020...Results - Conclusion - Funding: GlaxoSmithKline (208887). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Clinical • Combination therapy
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CD38 (CD38 Molecule) • TNFRSF4 (TNF Receptor Superfamily Member 4)
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Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
over4years
[VIRTUAL] DREAMM-5 platform trial: Belantamab mafodotin in combination with novel agents in patients with relapsed/refractory multiple myeloma (RRMM). (ASCO 2020)
Sub-studies 1 (combination with GSK3174998, OX40 agonist antibody) and 2 (combination with GSK3359609, ICOS agonist antibody) are currently enrolling. Sub-study 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics]) is projected to begin enrollment in the first half of 2020...Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Research Funding: GlaxoSmithKline
Clinical • Combination therapy
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CD38 (CD38 Molecule) • TNFRSF4 (TNF Receptor Superfamily Member 4)
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Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
over4years
[VIRTUAL] A first-in-human phase I study of the OX40 agonist GSK3174998 (GSK998) +/- pembrolizumab in patients (Pts) with selected advanced solid tumors (ENGAGE-1) (AACR-I 2020)
GSK998 +/- pembrolizumab was well tolerated, with evidence of target engagement; monotherapy clinical activity was limited. While combination responses may not be significantly greater than expected for pembrolizumab alone, responses were observed in some PD-1/L1 experienced pts and some with low PD-L1 expression. Given the low OX40 expression observed and preclinical evidence that increased expression improves activity of OX40 agonism, ongoing clinical evaluation of GSK998 will assess whether concurrent immune-stimulation or immunogenic cell death impacts OX40 expression and increases the efficacy of this agent.
Clinical • P1 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TLR4 (Toll Like Receptor 4) • TNFRSF4 (TNF Receptor Superfamily Member 4)
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PD-L1 expression
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Keytruda (pembrolizumab) • GSK3174998
over4years
Clinical • Trial suspension • Combination therapy
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CRP (C-reactive protein)
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Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
almost5years
Combination therapy • Enrollment change • Clinical
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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VENTANA PD-L1 (SP263) Assay
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
5years
Dreamm-5: Platform Trial Evaluating Belantamab Mafodotin (a BCMA-directed Immuno-conjugate) in Combination with Novel Agents in Relapsed or Refractory Multiple Myeloma (RRMM) (ASH 2019)
Initial substudies will include combinations with the T-cell activating checkpoint mAbs GSK3359609 (an IgG4 inducible T-cell costimulatory [ICOS] agonist antibody that is Fc optimized to selectively enhance T-cell function to enable antitumor responses), GSK3174998 (a humanized wild-type IgG1 anti-OX40 agonistic mAb), and a gamma-secretase inhibitor, Nirogacestat (PF-03084014, SpringWorks Therapeutics). Acknowledgments: Editorial assistance provided by Sarah Hauze, PhD, at Fishawack Indicia Ltd and funded by GSK. Study funded by GSK (208887); drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Combination therapy • IO biomarker
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CD38 (CD38 Molecule)
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Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
over5years
Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1) (clinicaltrials.gov)
P1; Trial completion date: May 2020 --> Dec 2022 | Trial primary completion date: May 2020 --> Dec 2022
Combination therapy • Trial completion date • Trial primary completion date • Clinical
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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VENTANA PD-L1 (SP263) Assay
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
6years
Combination therapy • Enrollment change • Clinical
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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VENTANA PD-L1 (SP263) Assay
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
almost7years
Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1) (clinicaltrials.gov)
P1; Trial primary completion date: Jun 2019 --> May 2020 | Trial completion date: Jun 2019 --> May 2020 | Initiation date: Jun 2016 --> Jun 2016
Combination therapy • Trial completion date • Trial primary completion date • Trial initiation date • Clinical
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MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
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MSI-H/dMMR
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VENTANA PD-L1 (SP263) Assay
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Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998