OncoMed has eight therapeutic candidates currently in clinical development targeting cancer stem cell pathways and immuno-oncology. All of the therapeutic candidates in our pipeline were discovered by OncoMed scientists using our in-depth knowledge of cancer biology, antibody engineering and a number of proprietary technologies to aid in ongoing drug discovery, candidate validation and predictive biomarker efforts.
Demcizumab is a monoclonal antibody that selectively targets Delta-like ligand 4 (DLL4), an activator of the Notch signaling pathway. The Notch pathway is known to be important in cancer stem cells and cancer. Blocking DLL4 has been shown in preclinical studies to result in anti-tumor activity via multiple mechanisms, including inhibiting cancer stem cell growth and promoting cell differentiation, disrupting angiogenesis and potentially enhancing anti-tumor immune response.
In Phase 1a clinical studies, single-agent demcizumab demonstrated early evidence of durable anti-tumor responses. Results from Phase 1b studies of demcizumab plus standard-of-care chemotherapy in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and pancreatic cancer demonstrated safety, anti-tumor responses and encouraging signals of prolonged survival benefit.
A Phase 2 trial to assess the efficacy of demcizumab with carboplatin and pemetrexed in 82 first-line non-squamous NSCLC is expected to read out in the first half of 2017. A Phase 1b trial assessing the combination of demcizumab plus pembrolizumab (anti-PD1, Keytruda®) in solid tumor patients is ongoing. Top-line results from the company’s Phase 2 clinical trial of demcizumab in combination with Abraxane® plus gemcitabine in previously untreated patients with metastatic pancreatic cancer did not meet the primary endpoint of progression-free survival. Additionally, the interim median overall survival analysis did not show a benefit for demcizumab in combination with Abraxane plus gemcitabine compared to the Abraxane, gemcitabine plus placebo arm. Clinical enrollment is complete in these studies.
Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.
The most recent public presentations of the demcizumab clinical studies include:
Tarextumab is a novel anti-cancer stem cell antibody that prevents signaling through both the Notch2 and Notch3 receptors. Tarextumab has been shown in preclinical models to inhibit cancer stem cell growth and promote cell differentiation, as well as disrupt tumor angiogenesis by inhibiting vascular pericytes.
Tarextumab is currently being studied in the randomized Phase 2 portion of the Phase 1b/2 PINNACLE trial, testing tarextumab in combination with etoposide and physician's choice of cisplatin or carboplatin in 145 first-line extensive stage small cell lung cancer (SCLC) patients. The Phase 1b portion of the PINNACLE clinical trial demonstrated that tarextumab is well tolerated in combination with standard-of-care chemotherapies. Data from the Phase 1b trial showed improved survival outcomes associated with higher doses of tarextumab versus low doses of tarextumab. In patients whose tumors had high in expression levels of key genes in the Notch pathway, improved survival trends were also observed. The Phase 2 PINNACLE trial will assess the predictive potential of these genes. The Phase 2 clinical trial of tarextumab plus standard of care chemotherapy in SCLC is ongoing and results from this trial are anticipated in the first half of 2017; additional information is listed here: Tarextumab ClinicalTrials.gov
Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK).
Public presentations of tarextumab data include:
Vantictumab targets the Wnt cancer stem cell pathway. In preclinical models, vantictumab reduces cancer stem cell frequency and induces differentiation of tumorigenic cells to cell types that are less tumorigenic and more susceptible to conventional chemotherapy. We have seen strong anti-tumor activity using vantictumab in combination with multiple types of approved therapies in patient-derived xenograft models, including pancreatic, breast, lung, melanoma, hepatocellular, ovarian, colorectal and other cancers. We have also observed synergies preclinically when vantictumab is combined with taxane-based chemotherapies. We believe vantictumab is the first monoclonal antibody designed to inhibit Wnt signaling to enter clinical testing.
OncoMed is conducting two Phase 1b clinical trials of vantictumab in combination with standard-of-care chemotherapy – a Phase 1b trial in HER2-negative breast cancer (vantictumab + paclitaxel) and a Phase 1b trial in advanced pancreatic cancer (vantictumab + gemcitabine + Abraxane®). Information about OncoMed's clinical studies of vantictumab is available here: Vantictumab ClinicalTrials.gov.
Public presentations on vantictumab clinical studies include:
Ipafricept selectively binds Wnt ligands that are activators of Wnt signaling. It is a fusion protein that consists of a portion of the Frizzled 8 receptor from the Wnt pathway fused to the Fc domain of a human IgG1. In multiple preclinical models, ipafricept has shown evidence of strong anti-tumor activity in solid tumors including pancreatic, breast, hepatocellular, ovarian, colorectal and other cancers, and reduction of CSC frequency, either as a single agent or when combined with approved therapies.
Two Phase 1b clinical trials of ipafricept are ongoing: one in pancreatic cancer (gemcitabine/nab-paclitaxel + ipafricept) and one in ovarian cancer (carboplatin/paclitaxel + ipafricept). In a Phase 1a clinical trial, ipafricept was well tolerated as a single agent and demonstrated evidence of Wnt pathway modulation and potential early single-agent activity manifested by prolonged stable disease. Links to the ongoing ipafricept clinical trials on clinicatrials.gov can be accessed here: Ipafricept ClinicalTrials.gov.
Public presentations of ipafricept data include:
Navicixizumab, OncoMed's anti-DLL4/VEGF bispecific targets both DLL4 in the Notch cancer stem cell pathway and vascular endothelial growth factor (VEGF) receptors. This antibody is intended to have anti-angiogenic plus anti-cancer stem cell and immunomodulatory activity. In a Phase 1a clinical trial, navicixizumab demonstrated single-agent anti-tumor activity and was safe enough to be administered on a continuous basis. We have initiated two Phase Ib clinical trials to assess the safety, preliminary efficacy, immunogenicity and pharmacokinetics of navicixizumab in combination with standard of care chemotherapy in ovarian and colorectal cancers. See clinical trials listings here: Navicixizumab ClinicalTrials.gov).
This program is part of OncoMed's collaboration with Celgene Corporation.
Public presentations on navicixizumab Anti-DLL4/VEGF bispecific studies include:
In 2007, we identified that the R-spondin, or RSPO, ligands signal through the LGR receptor family and have since identified antibodies to proteins in this family that modulate RSPO-LGR signaling. RSPO appears to be an oncogenic driver in several tumor types, particularly colon cancer. RSPO is associated with the activation of Wnt signaling and tumorigenesis. Anti-RSPO3 (OMP-131R10) is our lead program targeting the RSPO-LGR pathway. OncoMed initiated a Phase 1a/1b clinical study for its first antibody targeting the RSPO-LGR pathway, anti-RSPO3 (OMP-131R10). A proprietary biomarker to prospectively screen patients for expression of RSPO is being developed in conjunction with this clinical program. Anti-RSPO3 has demonstrated activity in preclinical models against a variety of major tumor types, including colon, lung and ovarian cancers. Information on OncoMed's anti-RSPO3 clinical program is available here: Anti-RSPO3 clinical program.
This program is part of OncoMed’s collaboration with Celgene Corporation.
Public presentations on anti-RSPO3 (OMP-131R10) include:
Bronticuzumab is a novel anti-cancer stem cell antibody that binds the Notch1 receptor. Blocking Notch1 has been shown in preclinical models to inhibit cancer stem cell growth, and promote cell differentiation, as well as to disrupt tumor angiogenesis. Notch1 signaling is prevalent in several solid tumor types, including certain breast, esophageal, colorectal, gastric, pancreatic and small cell lung cancers, as well as adenoid cystic carcinoma and cholangiocarcinoma. Single-agent anti-tumor activity was observed in OncoMed’s Phase 1a study of brontictuzumab in patients with certain advanced solid tumors, particularly in biomarker-defined patients whose tumors tested positive for overexpression of the activated form of Notch1. OncoMed is currently enrolling patients with metastatic colorectal cancer in a Phase 1b clinical trial intended to assess safety, preliminary efficacy and immunogenicity, as well as predictive and pharmacodynamics biomarkers of brontictuzumab in combination with trifluridine/tipiracil (Lonsurf®). Information on ongoing brontictuzumab clinical trials can be found here: Brontictuzumab ClinicalTrials.gov
OncoMed retains worldwide rights to develop brontictuzumab.
Public presentations of data from brontictuzumab studies include:
OncoMed has multiple new discovery and preclinical efforts advancing internally. Among the disclosed preclinical immuno-oncology compounds being advanced is an anti-TIGIT program in collaboration with Celgene. TIGIT (T-cell immunoreceptor with Ig and ITIM domains) blocks T-cells from attacking tumor cells, similar to the inhibitory protein PD-1. Our anti-TIGIT therapeutic is intended to activate the immune system, through multiple mechanisms, and enable anti-tumor activity. A Phase I clinical trial of our anti-TIGIT therapeutic candidate is expected to begin enrolling patients during the first half of 2017.
Public presentations of data from OncoMed's emerging pileine include:
OncoMed expects to file an Investigational New Drug Application for its wholly owned GITRL-Fc trimer in the first half of 2017. GITRL is a member of the tumor necrosis factor (TNF) family of ligands and functions to activate the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor) to enhance T-cell modulated immune responses. OncoMed’s GITRL-Fc agent is engineered using a novel single-gene linkerless GITRL trimer which is designed to enable effective GITR activation and robust anti-tumor immune response.