^
    9ms
    Immune modulation in solid tumors: a phase 1b study of RO6870810 (BET inhibitor) and atezolizumab (PD-L1 inhibitor). (PubMed, BMC Cancer)
    The combination of BET inhibitor RO6870810 with the checkpoint inhibitor atezolizumab presents an unfavorable risk-benefit profile for ovarian cancer and TNBC (triple-negative breast cancer) patients due to the increased risk of augmented or exaggerated immune reactions, without evidence for synergistic antitumor effects.
    P1 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1)
    |
    PD-L1 expression
    |
    Tecentriq (atezolizumab) • RG6146
    1year
    Prognosis and immunotherapeutic implications of molecular classification of cervical cancer based on immunophenoscore-related genes. (PubMed, J Biomol Struct Dyn)
    cluster2 had higher immune cell infiltration levels and better prognosis, with greater sensitivity to Cyclopamine, Imatinib, MG-13, Paclitaxel, PHA-665752, Rapamycin, Sorafenib, Sunitinib, and VX-680. In contrast, cluster3 had higher TTN and PIK3CA mutations and greater sensitivity to AZ628, Dasatinib, Doxorubicin, HG-6-64-1, JQ12, Midostaurin, PF-562271, TAE684, and WH-4-023. In conclusion, we developed a feasible risk score model based on IPS-related genes for cervical cancer prognosis and identified potential drugs for different cervical cancer subtypes.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PD-L2 (Programmed Cell Death 1 Ligand 2)
    |
    PIK3CA mutation
    |
    dasatinib • sorafenib • paclitaxel • imatinib • sunitinib • doxorubicin hydrochloride • midostaurin • sirolimus • AZ 628 • TAE-684 • cyclopamine • RG6146 • benzesulfonate (PF-562271) • PHA665752 • tozasertib (MK-0457)
    4years
    Phase Ib study of BET inhibitor RO6870810 with venetoclax and rituximab in patients with diffuse large B-cell lymphoma. (PubMed, Blood Adv)
    Complete response was observed in 8 patients (20.5%). Optimization of the treatment schedule and a better understanding of predictors of response would be needed to support broader clinical use.
    Clinical • P1 data • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ITGAM (Integrin, alpha M)
    |
    Venclexta (venetoclax) • Rituxan (rituximab) • RG6146
    almost5years
    A dose escalation study of RO6870810/TEN-10 in patients with acute myeloid leukemia and myelodysplastic syndrome. (PubMed, Leuk Lymphoma)
    For MDS, two patients experienced SD. Further development of RO as monotherapy was discontinued due to lack of efficacy, but combinations with other agents are under consideration.
    Clinical • Journal
    |
    ITGAM (Integrin, alpha M)
    |
    RG6146
    almost5years
    A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma. (PubMed, Br J Cancer)
    This trial establishes the safety, favourable pharmacokinetics, evidence of target engagement and preliminary single-agent activity of RO6870810. Responses in patients with NC, other solid tumours and DLBCL provide proof-of-principle for BET inhibition in MYC-driven cancers. The results support further exploration of RO6870810 as monotherapy and in combinations.
    Clinical • P1 data • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ITGAM (Integrin, alpha M)
    |
    MYC expression
    |
    RG6146
    5years
    [VIRTUAL] Open Label, Multicenter, Dose-Escalation/ Expansion Phase Ib Study to Evaluate Safety and Activity of BET Inhibitor RO6870810 (RO), Given As Monotherapy to Patients (pts) with Advanced Multiple Myeloma (ASH 2020)
    P1 | "Pts were refractory to immunomodulatory drugs (63%), proteasome inhibitors (46%), both (46%), or daratumumab (42%). Pharmacodynamics effects were evident at this dose, but as monotherapy in this R/R MM cohort, response rates were low and less durable. Future drug combination approaches may result in an improved benefit / risk ratio."
    P1 data • Clinical
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ITGAM (Integrin, alpha M)
    |
    MYC expression
    |
    Darzalex (daratumumab) • RG6146
    almost6years
    A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 (clinicaltrials.gov)
    P1, N=39, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | Trial completion date: Mar 2020 --> Aug 2019 | Trial primary completion date: Mar 2020 --> Aug 2019
    Clinical • Trial completion • Trial completion date • Trial primary completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2)
    |
    BCL2 expression • MYC expression
    |
    Venclexta (venetoclax) • Rituxan (rituximab) • RG6146
    over6years
    A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer (clinicaltrials.gov)
    P1, N=36, Terminated, Hoffmann-La Roche | N=116 --> 36 | Trial completion date: Jan 2021 --> May 2019 | Suspended --> Terminated | Trial primary completion date: Jan 2021 --> May 2019; Portfolio prioritization
    Clinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • MUC16 (Mucin 16, Cell Surface Associated) • CD14 (CD14 Molecule) • ITGAM (Integrin, alpha M)
    |
    ITGAM expression
    |
    Tecentriq (atezolizumab) • RG6146
    over6years
    A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 (clinicaltrials.gov)
    P1, N=39, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=94 --> 39
    Clinical • Enrollment closed • Enrollment change
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2)
    |
    BCL2 expression • MYC expression
    |
    Venclexta (venetoclax) • Rituxan (rituximab) • RG6146
    almost7years
    A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer (clinicaltrials.gov)
    P1; N=116; Suspended; Sponsor: Hoffmann-La Roche; Recruiting --> Suspended
    Trial suspension • Clinical
    |
    CD8 (cluster of differentiation 8) • MUC16 (Mucin 16, Cell Surface Associated) • CD14 (CD14 Molecule) • ITGAM (Integrin, alpha M)
    |
    ITGAM expression
    |
    Tecentriq (atezolizumab) • RG6146
    7years
    A Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (clinicaltrials.gov)
    P1; N=94; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Jul 2020 --> Mar 2020; Trial primary completion date: Jul 2020 --> Mar 2020
    Trial completion date • Trial primary completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2)
    |
    BCL2 expression • MYC expression
    |
    Venclexta (venetoclax) • Rituxan (rituximab) • RG6146
    7years
    A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer (clinicaltrials.gov)
    P1, N=116, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2020 --> Jan 2021 | Trial primary completion date: Jul 2020 --> Jan 2021
    Clinical • Trial completion date • Trial primary completion date • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • MUC16 (Mucin 16, Cell Surface Associated) • CD14 (CD14 Molecule) • ITGAM (Integrin, alpha M)
    |
    ITGAM expression
    |
    Tecentriq (atezolizumab) • RG6146