^
    28d
    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)
    P2, N=208, Active, not recruiting, GlaxoSmithKline | Trial completion date: Feb 2029 --> Mar 2027 | Trial primary completion date: Feb 2029 --> Apr 2025
    Trial completion date • Trial primary completion date
    |
    lenalidomide • Jemperli (dostarlimab-gxly) • pomalidomide • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
    11ms
    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)
    P2, N=209, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting | Phase classification: P1/2 --> P2 | N=464 --> 209 | Trial primary completion date: Feb 2026 --> Feb 2029
    Enrollment closed • Phase classification • Enrollment change • Trial primary completion date
    |
    lenalidomide • Jemperli (dostarlimab-gxly) • pomalidomide • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
    almost2years
    Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMM (clinicaltrials.gov)
    P1/2, N=9, Terminated, GlaxoSmithKline
    New P1/2 trial • Combination therapy
    |
    Blenrep (belantamab mafodotin-blmf) • GSK3174998
    2years
    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
    |
    lenalidomide • Jemperli (dostarlimab-gxly) • pomalidomide • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
    over2years
    Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1) (clinicaltrials.gov)
    P1; Active, not recruiting --> Completed
    Combination therapy • Trial completion • Metastases
    |
    MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
    |
    MSI-H/dMMR
    |
    PD-L1 IHC 22C3 pharmDx
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
    over2years
    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
    |
    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)
    |
    Keytruda (pembrolizumab) • GSK3174998
    3years
    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
    |
    IL10 (Interleukin 10) • TLR4 (Toll Like Receptor 4) • IL1R1 (Interleukin 1 receptor, type I)
    |
    Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
    over3years
    Study of a Combination of GSK1795091 and Immunotherapies in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=54, Completed, GlaxoSmithKline | Active, not recruiting --> Completed
    Trial completion
    |
    CRP (C-reactive protein)
    |
    Keytruda (pembrolizumab) • feladilimab (GSK3359609) • GSK1795091 • GSK3174998
    4years
    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
    |
    PD-1 (Programmed cell death 1) • ICOS (Inducible T Cell Costimulator)
    |
    Jemperli (dostarlimab-gxly) • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
    over4years
    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
    |
    MSI (Microsatellite instability) • ICOS (Inducible T Cell Costimulator)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • gemcitabine • paclitaxel • docetaxel • 5-fluorouracil • pemetrexed • Jemperli (dostarlimab-gxly) • bintrafusp alfa (M7824) • cobolimab (TSR-022) • feladilimab (GSK3359609) • GSK3174998
    over4years
    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
    |
    ICOS (Inducible T Cell Costimulator)
    |
    Jemperli (dostarlimab-gxly) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
    5years
    [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
    |
    CD38 (CD38 Molecule) • ICOS (Inducible T Cell Costimulator)
    |
    Jemperli (dostarlimab-gxly) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998