F. Hoffmann-La Roche is a global health-care company providing a broad spectrum of innovative medical solutions, operating worldwide under two division: Pharmaceuticals & Diagnostics.
Roche Major Oncology Drug Approvals
- In Sep 2020, US FDA approved Pralsetinib (Gavreto™) for the treatment of adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer. Later in Dec 2020, US FDA approved pralsetinib for the treatment of adult and paediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy.
- In Aug 2019, the US FDA granted accelerated approval to Entrectinib (ROZLYTREK, Genentech Inc.) for adults and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy.
- In June 2019, US FDA approved Polatuzumab vedotin (POLIVY®) for treatment of diffuse large B-cell lymphoma when used in combination with bendamustine and rituximab.
- In Oct 2016, FDA approved Atezolizumab (TECENTRIQ®, Genentech Inc.) for the treatment of people with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. In 2018, FDA approved drug as a first-line treatment for metastatic bladder cancer in people who can’t receive cisplatin-based chemotherapy and have high levels of PD-L1. Atezolizumab is also used to treat extensive stage small cell lung cancer and for the treatment of people with triple-negative breast cancer.
- In Dec 2015, US FDA approved Alectinib (ALECENSA® ) for ALK-Positive Non-Small Cell Lung Cancer, whose disease has worsened after, or who could not tolerate treatment with, another therapy called Xalkori (crizotinib).
- In Nov 2015, US FDA approved Cobimetinib (Cotellic) for the combination treatment of Advanced Melanoma.
- In 2013, FDA and EMEA both approved T-DM1/Kadcyla™ for the treatment of patients with HER2-positive metastatic breast cancer who have received prior treatment with Herceptin® and a taxane chemotherapy.
- In Nov 2013, U.S. FDA approved Obinutuzumab /GAZYVA™ / GA101 for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).
- In Jun 2012, FDA approved Pertuzumab/Perjeta™ for the use in combination with Transtuzumab and Docetaxel for the treatment of patients with HER2+ metastatic breast cancer who have not received prior anti-Her2 or chemotherapy for metastatic disease.
- In Jan 2012, FDA approved Vismodegib/Erivedge™ for the treatment of adults with advanced basal cell carcinoma when surgery is no longer an option. Vismodegib was developed as a result of collaboration between Curis and Genentech, signed in Jun 2003.
- In Aug 2011, Vemurafenib/ Zelboraf® get FDA approval for late stage melanoma. Cobas 4800 BRAF V600 mutation diagnostic test (Roche) is required.
- In 2006, Genentech and Plexxikon entered into an agreement to co-develop and market Vemurafenib / Zelboraf® (a B-Raf inhibitor).
- In 2004, FDA also approved Erlotinib/Tarceva® for patients with locally advanced or metastatic NSCLC and pancreatic cancer.
- In 2004, FDA approved Genentech’s Bevacizumab/Avastin® for metastatic cancer of the colon or rectum and in 2006 for NSCLC.
- In 1998, Genentech’s Trastuzumab/Herceptin® was FDA approved for HER2 positive metastatic breast cancer and in 2010, in combination with chemotherapy for people with metastatic stomach (gastric) cancer with tumors exhibiting high levels of HER2.
- In 1998, Capecitabine/Xeloda® was FDA approved for the treatment of metastatic breast cancer and in 2001 and 2005 for colorectal cancer and Duke’s colon cancer respectively.
Roche Active Clinical Stage Oncology Pipeline (26 Active Molecules)
| Molecule | Target | Phase | Key Indications Only | NCT Number | Molecule Type |
|---|---|---|---|---|---|
| Atezolizumab /Tecentriq / RG7446 | PD-L1 | III | Hepatocellular Carcinoma | NCT04487067 | Monoclonal Antibody |
| III | Urinary Tract Cancer | NCT02928406 | |||
| III | Ovarian Cancer | NCT02891824 | |||
| III | Metastatic Prostate Cancer | NCT03016312 | |||
| III | Renal Cell Carcinoma | NCT04338269 | |||
| III | Head & Neck Squamous Cell Cancer | NCT03452137 | |||
| Glofitamab / RG6026 | CD20, CD3 | III | Diffuse Large B-cell Lymphoma | NCT04408638 | Bispecific Antibody |
| I | Non-Hodgkin's Lymphoma | NCT03075696 | |||
| I | Follicular Lymphoma | NCT04246086 | |||
| Mosunetuzumab | CD20, CD3 | III | R/R Follicular Lymphoma | NCT04712097 | Bispecific Antibody |
| I/II | B-cell Non-Hodgkin Lymphoma | NCT03671018 | |||
| Tiragolumab / RG6058 | TIGIT | III | Non-Small Cell Lung Cancer | NCT04294810 | Monoclonal Antibody |
| III | Small Cell Lung Cancer | NCT04665856 | |||
| III | Esophageal Squamous Cell Carcinoma | NCT04543617 | |||
| II | Head & Neck Squamous Cell Cancer | NCT04665843 | |||
| II | Cervical Cancer | NCT04300647 | |||
| Inavolisib / RG6114 /GDC-0077 | PI3K alpha | II/III | Metastatic Breast Cancer | NCT04191499 | Small Molecule |
| Giredestrant / RG6171/GDC-9545 | SERD | III | ER+ HER2- Metastatic Breast Cancer | NCT04546009 | Small Molecule |
| Ipatasertib /RG7440 | AKT | III | Metastatic Prostate Cancer | NCT03072238 | Small Molecule |
| III | Breast Cancer | NCT03337724 | |||
| III | Triple-Negative Breast Cancer | NCT04177108 | |||
| II | Metastatic Gastric Cancer | NCT01896531 | |||
| II | Non-Small Cell Lung Cancer | NCT04467801 | |||
| Autogene cevumeran / iNeST / RG6180 | - | II | Advanced Melanoma | NCT03815058 | Vaccine |
| II | Advanced Colorectal Cancer | NCT04486378 | |||
| I | Pancreatic Cancer | NCT04161755 | |||
| Selicrelumab / RG7876 | CD40 | I | Pancreatic Cancer | NCT02588443 | Monoclonal Antibody |
| I | Advanced/Metastatic Solid Tumors | NCT02665416 | |||
| RG7827 / RO7122290 | FPA , 4-1BBL | I/II | Metastatic Colorectal Cancer | NCT04826003 | Fusion Antibody |
| Cibisatamab / RG7802 | CEA, CD3 | I | Colorectal Cancer | NCT03866239 | Bispecific Antibody |
| RG7769 / RO7121661 | PD1, TIM3 | I | Solid Tumors | NCT03708328 | Bispecific Antibody |
| RG6330 / GDC-6036 | KRAS G12C | I | Non-Small Cell Lung Cancer | NCT04449874 | Small Molecule |
| Colorectal Cancer | |||||
| Solid Tumors (KRAS G12C mutation) | |||||
| RG6323/ XmAb24306 | IL15/IL15Ra-Fc | I | Metastatic Solid Tumors | NCT04250155 | Fusion Protein |
| RG6296/ AFM26 / | BCMA, CD16a | I | R/R Multiple Myeloma | NCT04434469 | Bispecific Antibody |
| RG6292/ RO7296682 | CD25 (IL-2Rα) | I | Advanced Solid Tumors | NCT04158583 | Monoclonal Antibody |
| RG6286 / BLYG8824A | Undisclosed | I | Metastatic Colorectal Cancer | NCT04468607 | Small Molecule |
| RG6076 / RO7227166 | CD19, 4-1BBL | I | R/R B-Cell Non-Hodgkin's Lymphoma | NCT04077723 | Fusion Protein |
| RG6115 / RO7119929 | TLR7 | I | Hepatocellular Carcinoma | NCT04338685 | Small Molecule |
| Biliary Tract Cancer | |||||
| RG6007 / RO7283420 | HLA-A2-WT1, CD3 | I | Adult Acute Myeloid Leukemia | NCT04580121 | Bispecific Antibody |
| RG6139 / RO7247669 | PD1, LAG3 | I | Solid Tumors | NCT04140500 | Bispecific Antibody |
| Metastatic Melanoma | |||||
| Non-small Cell Lung Cancer | |||||
| Esophageal Squamous Cell Carcinoma | |||||
| Cevostamab / RG6160 / RO7425781 | FcRH5, CD3 | I | Multiple Myeloma | NCT04557150 | Bispecific Antibody |
| RG6194 / DHES0815A | HER2, CD3 | I | Breast Cancer | NCT03451162 | Bispecific Antibody |
| RG6232 / RO7293583 | TYRP1, CD3 | I | Metastatic Melanoma | NCT04551352 | Bispecific Antibody |
| Belvarafenib/ RG6185 / HM95573 | RAS | I | Advanced Melanoma | NCT04835805 | Small Molecule |
| RG6279/ RO7284755 | PD1, IL2v | I | Metastatic Solid Tumors | NCT04303858 | Fusion Protein |
Roche Active Oncology Pipeline Drug Description
- Atezolizumab (anti-PDL1, RG7446, MPDL3280A) is an engineered monoclonal antibody that targets the ligand PD-L1 (programmed death ligand 1) aiming to prevent cancer immune evasion.
- Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells.
- Glofitamab is in clinical development, as a monotherapy and in combination with other medicines, for the treatment of people with CD20 positive B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, and other blood cancers.
- Mosunetuzumab is an investigational CD20xCD3 T-cell engaging bispecific designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells.
- Tiragolumab is a monoclonal antibody designed to bind with TIGIT, a protein receptor on immune cells. Tiragolumab works as an immune amplifier, by potentially enhancing the body’s immune response.1 By binding to TIGIT, tiragolumab blocks its interaction with a protein called poliovirus receptor (PVR, or CD155) that can suppress the body’s immune response.4 Blockade of TIGIT and PD-L1 may synergistically enable the re-activation of T cells and enhance NK cell anti-tumour activity.
Tiragolumab is the first anti-TIGIT therapy to be granted Breakthrough Therapy Designation (BTD) by the FDA. - Inavolisib / RG6114 (GDC-0077) is a small molecule PI3 kinase (PI3K) inhibitor. Dysregulation of PI3K signaling is implicated in a broad range of human cancers, and activating mutations in the PI3K alpha-isoform gene (PIK3CA) are common oncogenic drivers.
- Giredestrant / GDC-9545 is a potent, orally available, selective estrogen receptor degrader developed for the treatment of ER-positive (ER+) breast cancer alone or combined with CDK4/6 inhibitors.
- Ipatasertib is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity.
- Autogene cevumeran or Individualised Neoantigen-Specific Therapy, iNeST (RG6180) is a messenger RNA (mRNA)-based, individually tailored, personalized cancer vaccine. Each vaccine will be made using unique neoantigen signatures from an individual patient’s tumor, which is expected to elicit an effective immune response against that patient’s tumor.
Autogene cevumeran is developed in collaboration with BioNTech SE - Selicrelumab (RG7876) is a fully human (IgG2) agonistic antibody against CD40. The antibody induces T cell-driven tumor killing by activation of CD40 on antigen-presenting cells which in turn prime T cells to attack the tumor.
- RG 7827 is a next generation antibody fusion protein that has an antibody-like structure, with one arm binding to fibroblast activated protein (FAP, which is a protein found in the stroma of many solid tumor types, and the other arm carrying the signaling molecule, 4-1BBL and is significantly more potent and efficacious than first generation, standard 4-1BB agonistic antibodies when compared side-by-side in preclinical models.
In preclinical models, combination of FAP-4-1BBL with T-cell bispecific antibodies leads to significant increases in T cell infiltration into the tumor, CD8/Treg ratio and anti-tumoral efficacy. We conclude that the tumor-targeted cross-linking of 4-1BB provides a safe and effective way for co-stimulation of T cells for cancer immunotherapy and its combination with T-cell bispecific antibodies may provide a convenient “off-the-shelf,” systemic cancer immunotherapy approach for many tumor types. - RG 7769 is an anti-programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM-3) bispecific antibody.
- XmAb24306 is an IL-15/IL-15Rα cytokine complex engineered designed for IL15/IL15R heterodimeric Fc-fusions display enhanced in vivo activity through increased exposure.
- XmAb 24306 is a recombinant fusion protein being developed by Xencor, in collaboration with Genentech, for the treatment of multiple oncology.
- RG6296 / AFM26 is a novel tetravalent, bispecific antibody designed to specifically enhance NK-cell anti-Multiple Myeloma activity by redirecting NK-cell lysis to BCMA, an antigen expressed on relapsed/refractory multiple myeloma cells.
- RG6292 is a monoclonal antibody that targets CD25 (IL-2Rα). The antibody mediates the depletion of regulatory T-cells (Tregs), a major suppressor of the anti-cancer immune response. RG6292 does not interfere with IL-2 signaling of other immune cells which are acting against the tumor.
- RG6279 is an antibody fusion protein blocking PD1 combined with an engineered interleukin-2 variant (IL2v) inducing immune-modulating activity.
- CD19-4-1BBL(RG6076) is a fusion protein targeting the 4-1BB ligand to cells bearing CD19 acting as an NK- and T-cell co-stimulator.
TLR7 agonist is an oral, small molecule immuno-modulator activating the TLR (toll-like receptor) 7. It stimulates the production of cytokines and may promote an inflammatory microenvironment, fostering T-cell activation and anti-tumor immunity. - RG6139 is a bispecific monoclonal antibody PD1 x LAG3 (RG6139) binds to the PD-1 and LAG-3 inhibitory checkpoint receptors on the surface of T-cells. PD1 x LAG3 MAb enable preferential targeting of dysfunctional effector T-cells over regulatory T-cells mediating immunosuppressive effects while restoring anti-tumor immune response.
- RG6194 is a bispecific antibody designed to target both the HER2-positive cells and CD3 on T cells. This dual-targeting antibody is designed to induce a polyclonal T-cell response against HER2-positive tumors. A phase I clinical trial is evaluating RG6194 for the treatment of metastatic HER2-positive cancers.
- RG6232 (TYRP1 x CD3) is a T-cell bispecific antibody targeting the tyrosinase-related protein 1 (TYRP1) expressed on melanoma cells and CD3 on T-cells.
- RG6185 (GDC-5573, HM95573) is a selective small-molecule inhibitor of the RAF family kinases designed to inhibit the MAPK pathway, which is frequently activated in human tumors and drives tumor growth. A phase I clinical trial is evaluating RG6185 for the treatment of solid tumors.
