A Phase 1b Dose Escalation Study of Vantictumab (OMP-18R5) in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of vantictumab when combined with nab-paclitaxel and gemcitabine.

Start Date01 Sep 2013

Sponsor / Collaborator

Mereo BioPharma 5, Inc.

NCT01957007

/ CompletedPhase 1

A Phase 1b Study of Vantictumab (OMP-18R5) in Combination With Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of vantictumab when combined with docetaxel.

Start Date01 Sep 2013

Sponsor / Collaborator-

NCT01973309

/ CompletedPhase 1

A Phase 1b Dose Escalation Study of Vantictumab (OMP-18R5) in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Breast Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of vantictumab when combined with paclitaxel.

Start Date01 Sep 2013

Sponsor / Collaborator-

100 Clinical Results associated with Vantictumab

100 Translational Medicine associated with Vantictumab

100 Patents (Medical) associated with Vantictumab

Literatures (Medical) associated with Vantictumab

02 Nov 2021·Expert opinion on therapeutic patentsQ2 · MEDICINE

Recent updates on Wnt signaling modulators: a patent review (2014-2020)

Q2 · MEDICINE

Review

Author: Patel, Bhumika D. ; Goswami, Vishalgiri G.

Introduction: Wnt signaling is a signal transduction pathway that plays a vital role in embryonic development and normal tissue preservation. Dysfunction of it gives rise to various diseases like cancer, Alzheimer's, metabolic and skeletal disorders, kidney and liver disease, etc. Thus, targeting Wnt pathway can be a potential approach to design and develop novel therapeutic classes.Areas covered: Authors provided an overview of Wnt modulators from 2014 to 2020. Different heterocyclic scaffolds and their pharmacology from a total of 104 PCT applications have been summarized.Expert opinion: The scientific community is working extensively to bring first in the class molecule to the market which targets Wnt pathway. 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, 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/clinical trials will define the role of the Wnt pathway in different therapeutic areas and open new opportunities.

01 Nov 2020·Breast cancer research and treatmentQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Mita, Alain ; Xu, Lu ; Zhang, Chun ; O'Shaughnessy, Joyce ; Osborne, Cynthia ; Diamond, Jennifer R ; Brachmann, Rainer K ; Kapoun, Ann M ; Richards, Donald ; Stagg, Bob ; Becerra, Carlos ; Henner, Randall ; Farooki, Azeez ; Mita, Monica ; Uttamsingh, Shailaja

PURPOSE:

Vantictumab is a monoclonal antibody that binds to frizzled (FZD) receptors and inhibits canonical WNT signaling. This phase Ib dose escalation study enrolled patients with locally recurrent or metastatic HER2-negative breast cancer who were treated with weekly paclitaxel in combination with escalating doses of vantictumab.

METHODS:

Patients were enrolled in dose escalation cohorts treated with weekly paclitaxel 90 mg/m² on days 1, 8 and 15 in combination with vantictumab 3.5-14 mg/kg days 1 and 15 or 3-8 mg/kg day 1 of every 28-day cycle. Primary endpoints were safety, dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics, efficacy and an exploratory biomarker analysis.

RESULTS:

Forty-eight female patients with a mean age of 54 were enrolled. The majority (66.6%) received prior chemotherapy for recurrent or metastatic disease; 45.8% were hormone receptor (HR)-positive, HER2-negative and 54.2% triple-negative. The most frequent adverse events related to any study treatment were nausea (54.2%), alopecia (52.1%), fatigue (47.9%), and peripheral neuropathy (43.8%). No DLTs occurred; however, 6 patients experienced fractures outside of the DLT window. The overall response rate was 31.3% and the clinical benefit rate was 68.8%. A 6-gene WNT pathway signature showed significant association with progression-free survival (PFS) and overall survival (OS) for the biomarker high versus biomarker low groups (PFS: p = 0.029 and OS: p = 0.00045, respectively).

CONCLUSIONS:

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 TRIAL REGISTRATION:

ClinicalTrials.gov registration: NCT01973309.

01 Jun 2020·Investigational new drugsQ3 · MEDICINE

A phase 1b dose escalation study of Wnt pathway inhibitor vantictumab in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic pancreatic cancer

Q3 · MEDICINE

Article

Author: O'Neil, Bert H ; Berlin, Jordan ; Dotan, Efrat ; Cardin, Dana B ; Shahda, Safi ; Lenz, Heinz-Josef ; Kapoun, Ann M ; Davis, S Lindsey ; Cohen, Steven J ; Stagg, Robert J ; Messersmith, Wells A

Summary:

Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. This phase Ib study evaluated vantictumab in combination with nab-paclitaxel and gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma. Patients received vantictumab at escalating doses in combination with standard dosing of nab-paclitaxel and gemcitabine according to a 3 + 3 design. A total of 31 patients were treated in 5 dosing cohorts. Fragility fractures attributed to vantictumab occurred in 2 patients in Cohort 2 (7 mg/kg every 2 weeks), and this maximum administered dose (MAD) on study was considered unsafe. The dosing schedule was revised to every 4 weeks for Cohorts 3 through 5, with additional bone safety parameters added. Sequential dosing of vantictumab followed by nab-paclitaxel and gemcitabine was also explored. No fragility fractures attributed to vantictumab occurred in these cohorts; pathologic fracture not attributed to vantictumab was documented in 2 patients. The study was ultimately terminated due to concerns around bone-related safety, and thus the maximum tolerated dose (MTD) of the combination was not determined. The MAD of vantictumab according to the revised dosing schedule was 5 mg/kg (n = 16).

News (Medical) associated with Vantictumab

17 Apr 2017

·www.biospace.com

When It Rains, It Pours: Bay Area’s OncoMed Tanks Again as Lung Cancer Med Fails Phase II, Discontinues Phase I Study

April 17, 2017 By Alex Keown , BioSpace.com Breaking News Staff REDWOOD CITY, Calif. – Shares of OncoMed Pharmaceuticals are down more than 18 percent this morning after the company announced its mid-stage combination lung cancer treatment failed to meet endpoints. OncoMed said tarextumab (anti-Notch2/3, OMP-59R5) in combination with etoposide and a chemotherapy drug to treat patients with extensive-stage small cell lung cancer showed results that were “undifferentiated from those of chemotherapy plus placebo.” As a result, the company said the trial did not meet primary endpoints of progression-free survival, nor secondary endpoints of overall survival. The median progression-free survival for tarextumab plus chemotherapy was 5.6 months versus 5.5 months for chemotherapy plus placebo. Overall response rates were 68.5 percent and 70.8 percent in the tarextumab and placebo arms respectively, the company said. Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. The drug is part of OncoMed’s collaboration with GlaxoSmithKline . Small cell lung cancer is expected to make up between 10 and 15 percent of the 224,390 newly diagnosed lung cancer cases and the 158,080 deaths estimated to occur in the U.S. Current standard of care in treating small cell lung cancer is the chemotherapeutic etoposide in combination with either cisplatin or carboplatin. “Small cell lung cancer is a very difficult-to-treat disease and unfortunately, tarextumab did not show benefit over placebo in this Phase 2 trial,” Paul Hastings , OncoMed’s chairman and chief executive officer said in a statement. Additionally, OncoMed said it will discontinue enrollment in the Phase 1b clinical trial of brontictuzumab (anti-Notch1, OMP-52M51) in combination with trifluridine/tipiracil (Lonsur) in third-line colorectal cancer patients. The combination of brontictuzumab plus chemotherapy was not tolerable in this patient population. April has not been kind to OncoMed. On April 10, the company announced its partnership with Bayer to develop two drugs, vantictumab and ipafricept , both Wnt pathway inhibitors, had ended due to “strategic reasons.” With Bayer’s withdrawal, OncoMed retains worldwide rights to both drugs. Also on April 10, the company announced it was terminating a Phase II trial testing demcizumab in combination with Abraxane as a first-line treatment in metastic pancreatic cancer after the drug failed to meet endpoints. Due to the events announced today and last week, Hastings said the company will undergo an immediate comprehensive portfolio prioritization review. “The immediate task ahead is to thoroughly examine the available data, our resources and the opportunities to re-focus our efforts. We ended the first quarter of 2017 with $156.9 million in cash and short-term investments,” Hastings said.

Phase 2Clinical ResultPhase 1Phase 3Clinical Trial Failure

04 Sep 2014

·www.biospace.com

Redwood City’s OncoMed Pharmaceuticals, Inc. Moves Forward On Drug Trials Halted Due To Side Effects

September 5, 2014 By Krystle Vermes , BioSpace.com Breaking News Staff California-based OncoMed Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration has removed the partial hold on its ipafricept Phase 1 clinical trials. As a result, OncoMed will continue enrollment, and patients will begin participating in experiments within the next few weeks. “With important input from our clinical investigators and academic bone experts, the OncoMed team has developed modified study parameters intended to avoid potential risks while allowing us to evaluate the therapeutic impact of ipafricept for patients with pancreatic, hepatocellular and ovarian cancers in combination with standard therapy,” said Jakob Dupont , M.D., OncoMed’s Chief Medical Officer. “We appreciate the FDA’s prompt response to our submission and their acceptance of our proposed amendments to the trial protocols.” OncoMed gave the FDA a clinical safety and efficacy package for the drug. In turn, the FDA placed the partial clinical trial on hold. Modified dosing regimens, risk mitigation measures and modified enrollment criteria were the amendments of the Phase 1b trials. On June 13, OncoMed announced that it would voluntarily be halting enrollment in its Phase 1 vantictumab and ipafricept Wnt pathway programs. This came after reported incidents of mild-to-moderate bone adverse events. After the FDA looked at more data and amended study protocols given to it by OncoMed, it decided to remove the partial hold on the clinical trials. “We expect enrollment in our first-in-class Wnt pathway programs, ipafricept and vantictumab, to be back underway soon,” said Paul J. Hastings , Chairman and Chief Executive Officer of OncoMed. “The Wnt pathway represents a highly promising target for disrupting cancer stem cell activity and inducing tumor differentiation. As we advance ipafricept and vantictumab through clinical studies in combination with standard of care, we expect to generate key data from these Phase 1b studies that will support a potential opt-in by our partner Bayer as well as late-stage clinical development.” Ipafricept is a fusion protein that inhibits a signaling pathway in cancer called the Wnt pathway. It binds to ligands that are activators in Wnt signaling. Patients who received ipafricept in a Phase 1a study tolerated the treatment well, and experimentations showed that the fusion protein demonstrated on-target Wnt pathway modulation. OncoMed Pharmaceuticals is dedicated to discovering and developing therapeutics that target cancer stem cells. The company has five anti-cancer products in clinical development. var switchTo5x=true; stLight.options({publisher: "0341611e-38a4-415d-9e18-75e093ff27e0", doNotHash: false, doNotCopy: false, hashAddressBar: false});

Phase 1

100 Deals associated with Vantictumab

External Link

KEGG	Wiki	ATC	Drug Bank
D10410	Vantictumab	-	DB12956

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic breast cancer	Phase 1	United States	-	01 Sep 2013
Recurrent Non-Small Cell Lung Cancer	Phase 1	United States	-	01 Sep 2013
Pancreatic Cancer	Phase 1	United States	Mereo BioPharma 5, Inc.	01 Sep 2013
Breast Cancer	Phase 1	-	Bayer AG	-
Non-Small Cell Lung Cancer	Phase 1	-	Bayer AG	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01973309 (Pubmed \| Breast Cancer Res \| Breast Cancer Res Treat) Manual	Phase 1	Metastatic HER2-Negative Breast Carcinoma HER2-negative	48	paclitaxel+vantictumab	lawwzxwuep(ipncugudlj) = werodrnlmx vnhfjukzxf (adnofmkgpg ) View more	Positive	01 Nov 2020
NCT02005315 (Pubmed \| Invest New Drugs) Manual	Phase 1	Metastatic Pancreatic Cancer First line	31	nab-paclitaxel+gemcitabine+vantictumab	xvmeyjkfhs(ztxmzdkepz) = not determined alujlysvqz (bgupanlfur ) View more	Negative	01 Jun 2020
NCT02005315 (ASCO_GI2019)	Phase 1	Pancreatic Cancer	31	Vantictumab + Nab-P + G	dvjkuksvie(dmciuioryg) = grade 3 dehydration in 1 of 9 patients in cohort 4 (5 mg/kg q4w) rhzvipuecq (xlygruglaa ) View more	Negative	29 Jan 2019
NCT01973309 (ASCO2016)	Phase 1	Metastatic HER2-Negative Breast Carcinoma	23	Paclitaxel	fmgoofcigm(hvlaycethb) = n = 3 zswaesrqpb (oeujwjgeeq ) View more	-	20 May 2016

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