vantictumab (OMP-18R5) / Mereo Biopharma, Novartis - LARVOL DELTA

A phase Ib dose escalation study of vantictumab (VAN) in combination with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients with previously untreated stage IV pancreatic cancer. (ASCO-GI 2019) - P1b; "The MTD of VAN plus Nab-P and G was not determined, but the maximum administered dose (MAD) of VAN, 7 mg/kg every 2 weeks, was considered unsafe related to bone toxicity, a known effect of WNT inhibition. After the study was revised, the MAD was 5 mg/kg every 4 weeks, with no protocol-specified bone toxicity observed (n = 16)."

Clinical • Combination therapy • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

A phase Ib dose escalation study of vantictumab (VAN) in combination with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients with previously untreated stage IV pancreatic cancer. (ASCO-GI 2019) - P1b; "The MTD of VAN plus Nab-P and G was not determined, but the maximum administered dose (MAD) of VAN, 7 mg/kg every 2 weeks, was considered unsafe related to bone toxicity, a known effect of WNT inhibition. After the study was revised, the MAD was 5 mg/kg every 4 weeks, with no protocol-specified bone toxicity observed (n = 16)."

Clinical • Combination therapy • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Recent updates on Wnt signaling modulators: a patent review (2014-2020). (PubMed, Expert Opin Ther Pat) - "Lorecivivint, Wnt inhibitor, for the treatment of knee osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules like LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical development for the treatment of cancer. Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of relapsed or refractory synovial sarcoma while OMP-18R5 is under Phase I for metastatic breast cancer. Ongoing preclinical and clinical trials will define the role of the Wnt pathway in different therapeutic areas and have opened new opportunities."

Journal • Review • Alopecia • Alzheimer's Disease • Breast Cancer • CNS Disorders • Hepatology • Immunology • Nephrology • Oncology • Osteoarthritis • Pain • Renal Disease • Rheumatology • Sarcoma • Solid Tumor • Synovial Sarcoma

[VIRTUAL] Analysis of clinical trials targeting the Wnt signaling pathway for cancer therapy (ASHP 2020) - "The most commonly used drugs, investigated in 3 or more clinical trials included DKN-01 [DKK1 neutralizing monoclonal antibody] (9.9%), PRI-724 [CBP/ β-catenin complex inhibitor] (4%), OMP-54F28 [Decoy Receptor for Wnt lignads] (4%), Vantictumab [monoclonal antibody against Frizzled receptors] (4%), Cirmtuzumab [monoclonal antibody against ROR1] (4%), and BHQ880 [monoclonal antibody against DKK1] (3%). Based on our analysis, we reckon that DKK1 is the most investigated Wnt pathway target in cancer clinical trials, with DKN-01 being the most explored drug. Out of the 91 studies, the highest number of trials were carried out in colorectal cancer, followed by multiple myeloma. The preponderance of the clinical trials in early phases and active status could be the possible reasons for the deficit of Wnt pathway modifiers for cancer therapy in clinical practice."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Hepatology • Leukemia • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor • DKK1 • ROR1 • SPON1

Adipocytes sustain pancreatic cancer progression through a non-canonical WNT paracrine network inducing ROR2 nuclear shuttling (AACR 2018) - "...Vantictumab, an anti-Frizzled monoclonal antibody, reduced ROR2 nuclear translocation and in turn the EMT and aggressiveness in HPDE and HPDE/KRAS cells. We demonstrated that adipocytes could induce EMT and aggressiveness in models of pancreatic preneoplastic lesions by orchestrating a complex paracrine signaling of soluble modulators of the non-canonical WNT signaling pathway that determine, in turn, the activation and nuclear translocation of ROR2. We demonstrated that adipocytes could induce EMT and aggressiveness in models of pancreatic preneoplastic lesions by orchestrating a complex paracrine signaling of soluble modulators of the non-canonical WNT signaling pathway that determine, in turn, the activation and nuclear translocation of ROR2. This signaling pathway could represent a novel target for pancreatic cancer chemoprevention. Most importantly, these factors could serve as novel biomarkers toselect a risk population among obese subjects for screening and, thus,...&q

Pancreatic Cancer

Wnt antagonists synergize with immune checkpoint inhibitors to enhance anti-tumor responses (AACR 2018) - "Here, we show that in various syngeneic murine tumor models, targeting Wnt signaling using the Fzd receptor monoclonal antagonist antibody, OMP-18R5 (vantictumab) or the pan-Wnt decoy receptor Fc fusion protein OMP-Fzd8-Fc (ipafricept) in combination with immune checkpoint inhibitors anti-CTLA-4 or anti-PD1 induce synergistic anti-tumor responses leading to decreased tumor volume and increased infiltration of activated CD8+ T cells into the tumor microenvironment. More importantly, we demonstrate that anti-PD1 and the Wnt antagonists decrease immune suppressive myeloid cell populations, which may enhance therapeutic efficacy and anti-tumor responses. Therefore, these results suggest that co-targeting Wnt and immune checkpoint proteins may provide valuable opportunities for novel combination strategies for immunotherapeutic clinical development."

Checkpoint inhibition • IO Biomarker • PD(L)-1 Biomarker • Oncology

Frizzled receptors in tumors, focusing on signaling, roles, modulation mechanisms, and targeted therapies. (PubMed, Oncol Res) - "However, the occurrence of fragility fractures in patients treated with Fzd-targeted agents such as OMP-54F28 and OMP-18R5 limits the development of this combination. Along with new insights on signaling, roles, and modulation mechanisms of Fzds in human tumors, more Fzd-related therapeutic targets will be developed."

Journal • Musculoskeletal Diseases • Oncology

Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer. (PubMed, Breast Cancer Res Treat) - P1b | "The combination of vantictumab and weekly paclitaxel was generally well tolerated with promising efficacy; however, the incidence of fractures limits future clinical development of this particular WNT inhibitor in metastatic breast cancer."

Clinical • Journal • P1 data • Alopecia • Breast Cancer • Dermatopathology • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Diseases • Oncology • Pain • Solid Tumor • Triple Negative Breast Cancer

Phase 1b study of WNT inhibitor vantictumab (VAN, human monoclonal antibody) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC) (ESMO 2016) - P1b; "A revised safety plan appears to have addressed bone toxicity encountered early in the study. Updated results, including predictive biomarker analyses in pt tumors, with PFS and overall survival, will be presented."

Biomarker • Clinical • Biosimilar • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Oncomed announces multiple abstracts accepted for presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Among the abstracts accepted for presentation are Phase 1a data for single-agent brontictuzumab (anti-Notch1, OMP-52M51) in advanced solid tumors, including initial results from an expansion cohort of patients whose tumors demonstrate an overexpression of the activated form of Notch1 as measured by a companion biomarker.  In addition, biomarker data for vantictumab (anti-Fzd7, OMP-18R5) in non-small cell lung cancer, as well as results of preclinical studies for OncoMed’s anti-DLL4/VEGF bispecific (OMP-305B83), will also be presented."

Anticipated conference • Anticipated P1 data • Anticipated preclinical • Biomarker • Non Small Cell Lung Cancer • Oncology

A Dose Escalation Study of OMP-18R5 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=35; Completed; Sponsor: OncoMed Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed; N=44 ➔ 35; Trial primary completion date: Dec 2015 ➔ May 2014

Enrollment change • Trial completion • Trial primary completion date • Biosimilar • Oncology

Morphosys: J.P. Morgan Healthcare Conference (Morphosys) - Anticipated data from P1 trial for solid tumors in 2014; Anticipated data from P1 trial for pancreatic cancer in 2015; Anticipated data from P1 trial for NSCLC in 2015; Anticipated data from P1 trial for breast cancer in 2015

Anticipated P1 data • Breast Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

Morphosys: BioEquity Europe (Morphosys) - Anticipated data from P1 trial (NCT01973309) for breast cancer in 2015; Anticipated data from P1 trial (NCT01957007) for NSCLC in 2015; Anticipated data from P1 trial (NCT02005315) for pancreatic cancer in 2015; Anticipated data from P1 trial (NCT01345201) for solid tumors in 2016

Anticipated P1 data • Breast Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

Oncomed: Q2 FY 2014 Results (OncoMed) - "Voluntarily halted vantictumab (Anti-Fzd7, OMP-18R5) and ipafricept clinical trials due to observed mild-to-moderate bone adverse safety events.  The FDA concurred with the company's actions and placed the programs on partial clinical hold.  The company continues to dose vantictumab and ipafricept to existing patients in their respective single-agent Phase 1a clinical trials who have remained on treatment for extended periods of time without disease progression and without significant drug-related adverse events. The company is working diligently with investigators and the FDA towards restarting all trials"

Adverse events • Trial status • Oncology

OncoMed: Q2 FY 2016 Results (OncoMed) - Anticipated initial data presentation from P1b trial (NCT02005315) of vantictumab in combination with nab-paclitaxel and gemcitabine for pancreatic cancer at ESMO (October 7-11, 2016)

Anticipated P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

OncoMed: ASCO 2016 (OncoMed) - "Vantictumab can be safely administered at pharmacologically active doses in combination with paclitaxel to patients with advanced HER2-negative breast cancer"; "Fatigue, constipation, diarrhea and nausea were the most commonly reported related toxicities. Vantictumab does not appear to worsen typical paclitaxel side effects"; "A revised bone safety plan, triggered by two fragility fractures, resulted in all patients receiving bone-protective therapy either at baseline or by end of Cycle 1. No further fragility fractures were observed"; "Paclitaxel did not appear to influence the pharmacokinetics of vantictumab"; "Encouraging anti-tumor activity was seen, both with dosing of every 2 and 4 weeks"

P1 data • Breast Cancer • Oncology

OncoMed: Clinical Trial Update (OncoMed) - “Vantictumab is well tolerated, Further dose escalation is ongoing”; “Vantictumab clearance is dose-dependent, consistent with target-mediated disposition”; “Vantictumab has pharmacodynamic (PD) effects on hair follicles, PD effects are consistent with Wnt biology, PD effects extend beyond serum exposure”; “Target efficacious dose was reached at dose level of 10 mg/kg every three weeks, C_max is PK driver of efficacy n nonclinical efficacy models” “Vantictumab has PD effects on bone, as evidenced by β-CTX increases, C_min (or time above a certain threshold appears to be the PK driver of toxicity”; “Increased bone turnover can be safely managed through careful monitoring, prophylactic Vitamin D and calcium supplements, and administration of zoledronic acid, if indicated”; “Prolonged stable disease in 3 patients with neuroendocrine tumors may represent single-agent activity”

P1 data • Oncology

Vantictumab: Anticipated expiry of patents in US related to composition-of-matter, method-of-use and polynucleotides in 2029 (OncoMed) - Annual Report 2016: Anticipated expiry of patents in US and ex-US related to vantictumab, certain of its uses, and/or related biomarkers between 2024 and 2036

Anticipated patent expiry • Oncology

Oncomed: Q2 FY 2014 Results (OncoMed) - Anticipated discussions with investigators and the FDA to resume enrollment and dosing in vantictumab and ipafricept programs in H2 2014

Anticipated FDA event • Oncology

OncoMed: ESMO 2016 (OncoMed) - "Encouraging anti-tumor activity was seen in patients, with an overall unconfirmed response rate of 48%"

P1 data • Oncology • Pancreatic Cancer

OncoMed: Clinical Trial Update (OncoMed) - “Vantictumab is well tolerated, Further dose escalation is ongoing”; “Vantictumab clearance is dose-dependent, consistent with target-mediated disposition”; “Vantictumab has pharmacodynamic (PD) effects on hair follicles, PD effects are consistent with Wnt biology, PD effects extend beyond serum exposure”; “Vantictumab has PD effects on bone, as evidenced by β-CTX increases”; “Increased bone turnover can be safely managed through careful monitoring, prophylactic Vitamin D and calcium carbonate, and administration of zoledronic acid, if indicated”; “Prolonged stable disease in 3 patients with neuroendocrine tumors may represent single-agent activity”

P1 data • Oncology

OncoMed: Q4 FY 2015 Results (OncoMed) - Anticipated data from P1 trial (NCT02005315) for pancreatic cancer in 2016; Anticipated data from P1 trial (NCT01973309) for breast cancer in 2016

Anticipated P1 data • Breast Cancer • Oncology • Pancreatic Cancer

OncoMed: Cowen & Company Healthcare Conference (OncoMed) - "Vantictumab"; "Interim Phase 1 Clinical Data: Ongoing Phase 1a Study, N=29 (Dose levels: 0.5 to 15 mg/kg, Safety: Vantictumab is well tolerated, Effective bone protection strategy, Biomarker: Modulation of WNT pathway in patient samples, Efficacy: Single-agent activity in 3/3 NET pts (pNET and Carcinoid)" 

P1 data • Oncology

OncoMed says FDA lifts partial hold on cancer drug trials (Reuters) - "OncoMed Pharmaceuticals Inc said the U.S. Food and Drug Administration lifted a partial hold on patient enrolments for three trials testing its experimental cancer drug, vantictumab. Enrolment of new patients is expected to resume in the next few weeks pending revised trial protocol approvals..."

Anticipated enrollment status • FDA event • Non Small Cell Lung Cancer • Oncology

MorphoSys: Company Update (Morphosys) - Anticipated data from P1 trial (NCT01957007) for NSCLC in 2015; Anticipated data from P1 trial (NCT02005315) for pancreatic cancer in 2015; Anticipated data from P1 trial (NCT01345201) for solid tumors in 2016

Anticipated P1 data • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer