On October 10, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported the presentation of interim clinical data from its ongoing Phase 1b trials of ipafricept (FZD8-Fc, OMP-54F28) and vantictumab (anti-Fzd, OMP-18R5) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress (Press release, OncoMed, OCT 10, 2016, View Source [SID:SID1234515712]).

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Ipafricept and vantictumab are first-in-class Wnt pathways inhibitors that are each being tested in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with previously untreated metastatic pancreatic cancer. Each Phase 1b clinical trial is designed as a dose-escalation study to primarily assess safety and tolerability. Secondary objectives include a preliminary assessment of efficacy and exploratory objectives include the identification of pharmacodynamic and predictive biomarkers.

"In the pancreatic cancer setting, ipafricept and vantictumab in combination with standard-of-care chemotherapy have demonstrated acceptable safety and encouraging early signs of efficacy and biomarker effects," said Jakob Dupont, M.D., Chief Medical Officer. "The data presented at ESMO (Free ESMO Whitepaper), alongside the data presented at ASCO (Free ASCO Whitepaper) for ipafricept and vantictumab, provide evidence supporting the Phase 2 readiness of each drug. Upon the completion of additional dose cohorts and subsequent follow-up, we look forward to presenting an opt-in package to our partner Bayer for these distinct Wnt pathway inhibitors in the first half of next year."

Ipafricept and vantictumab are both part of OncoMed’s collaboration with Bayer Pharma AG. Bayer can elect to exercise its options on ipafricept and vantictumab through completion of Phase 1b trials.

Ipafricept — Interim Phase 1b Data in Pancreatic Cancer
The ipafricept Phase 1b clinical trial has enrolled a total of 22 patients in four dose cohorts. Median follow up for the subjects was 5.9 months (range 0.97-17.5months) as of the data cut-off of August 1, 2016.

Safety
Interim safety results showed that the combination of ipafricept with chemotherapy was well tolerated. The most common toxicities were fatigue, nausea and decreased appetite and vomiting. No Grade 4 or 5 ipafricept-related toxicities were observed. Ipafricept did not appear to enhance chemotherapy-related toxicities.

Following the incidence of bone fractures in the Phase 1a clinical trials of Wnt inhibitors, OncoMed implemented an enhanced bone safety plan that includes monitoring of blood bone markers and bone density, and the administration of zoledronic acid bone protection in at-risk patients. Twelve of 22 patients received bone protective therapy on study and no fragility fractures were observed.

A maximum-tolerated dose has not yet been established and a fourth cohort is currently enrolling.

Efficacy
An interim efficacy assessment demonstrated evidence of anti-tumor effects for the combination of ipafricept with chemotherapy. Of the 18 patients evaluable for response, the overall response rate was 39 percent with seven patients achieving partial response. Another eight patients have achieved stable disease for a clinical benefit rate of 83 percent. Early evidence of durability was observed, with nine patients on study greater than 168 days and two patients on study for greater than one year. Progression-free survival (PFS) and overall survival (OS) data are not yet mature. At the time of the data cut-off eight subjects were still on study treatment.

Biomarker analysis
Interim analysis showed that patients with higher expression of Wnt pathway genes at baseline had greater than 40 percent reduction in tumor size compared to those patients with lower Wnt pathway gene expression at baseline, suggesting activated Wnt pathway signaling at baseline may be predictive of patients with a more favorable response to treatment.

A poster discussion of data from the ipafricept Phase 1b clinical trial was presented on Sunday, October 9, during the Developmental Therapeutics session in a poster titled, "Phase 1b study of WNT inhibitor ipafricept (IPA, decoy receptor for WNT ligands) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (PC)" (Abstract #3410).

Vantictumab – Interim Phase 1b Data in Pancreatic Cancer:
The vantictumab Phase 1b clinical trial has enrolled a total of 24 patients in four dose cohorts. As of the data cut-off of August 1, 2016 for results reported at ESMO (Free ESMO Whitepaper), median follow up for subjects was 5.9 months (range: 0.77-28.5 months).

Safety
Interim safety results showed that the combination of vantictumab with chemotherapy was well tolerated. The most common vantictumab-related toxicities were fatigue, nausea and dysgeusia. No Grade 4 or 5 vantictumab-related toxicities were observed. Further, vantictumab did not appear to enhance chemotherapy-related toxicities.

Following the incidence of bone fractures in the Phase 1a clinical studies of Wnt inhibitors, OncoMed implemented an enhanced bone safety plan that includes monitoring of blood bone markers and bone density, and the administration of zoledronic acid bone protection in at-risk patients. Seventeen of 24 patients received bone protective therapy and no fragility fractures have been observed.

A maximum-tolerated dose has not yet been established and a fifth cohort is currently enrolling.

Efficacy
An interim efficacy assessment demonstrated evidence of anti-tumor effects for the combination of vantictumab with chemotherapy. Of the 21 patients evaluable for response, the overall response rate was 48 percent with 10 patients achieving partial response. Further, the clinical benefit rate was 86 percent as an additional eight patients achieved stable disease. PFS and OS data are not yet mature. Nine of 24 patients were on study greater than 168 days with two patients on study for more than a year. At the time of the data cut-off five subjects were still on study treatment.

Biomarker analysis
Exploratory interim analysis of baseline tumors suggested OncoMed’s three-gene predictive biomarker successfully identified patients with better overall responses. Of the eight patients whose tumors were positive for the biomarker, seven achieved partial responses and one achieved stable disease.

Data from the vantictumab Phase 1b clinical trial were presented on Saturday, October 8, during the Gastrointestinal Tumors session in a poster titled, "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)" (Abstract #3412).