This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with sorafenib. OMP-54F28 will be administered IV on Day 1 of each 21-day cycle. The planned dose levels of OMP-54F28 are 5 and 10 mg/kg. Depending on safety in this study, additional lower or intermediate dose levels may be evaluated.

Start Date01 Jan 2014

Sponsor / Collaborator-

NCT02092363

/ CompletedPhase 1

A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Paclitaxel and Carboplatin in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with paclitaxel and carboplatin. OMP-54F28 will be administered IV on Days 1 of each 21-day cycle. Paclitaxel (175 mg/m2) and carboplatin (AUC = 5 mg/mL • min) will be administered IV on Day 1 of each cycle. A total of 6 cycles of paclitaxel and carboplatin will be given. Additional cycles may be given as per institutional standard of care after discussion with the Medical Monitor. Treatment with OMP-54F28 will continue after completion of treatment with paclitaxel and carboplatin. The planned dose levels of OMP-54F28 are 5 and 10 mg/kg.

Start Date01 Jan 2014

Sponsor / Collaborator-

NCT02050178

/ CompletedPhase 1

A Phase 1b Dose Escalation Study of OMP-54F28 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 OMP-54F28 when combined with nab-paclitaxel and gemcitabine. OMP-54F28 will be administered IV on Days 1 and 15 of each 28-day cycle. Nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered IV on Days 1, 8, and 15 of each cycle. The planned dose levels of OMP-54F28 are 3.5 mg/kg and 7.0 mg/kg.

Start Date01 Nov 2013

Sponsor / Collaborator-

100 Clinical Results associated with Ipafricept

100 Translational Medicine associated with Ipafricept

100 Patents (Medical) associated with Ipafricept

Literatures (Medical) associated with Ipafricept

15 Oct 2020·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

Phase Ib Study of Wnt Inhibitor Ipafricept with Gemcitabine and nab-paclitaxel in Patients with Previously Untreated Stage IV Pancreatic Cancer

Q1 · MEDICINE

Article

Author: Weekes, Colin ; Cohen, Steven J. ; Cardin, Dana B. ; Shahda, Safi ; Brachmann, Rainer K. ; Dotan, Efrat ; Messersmith, Wells ; Denlinger, Crystal S. ; Kapoun, Ann M. ; Astsaturov, Igor ; Stagg, Robert J. ; Lenz, Heinz-Josef ; O'Neil, Bert ; Uttamsingh, Shailaja

Abstract:

Purpose::

The recombinant fusion protein ipafricept blocks Wnt signaling, and in combination with gemcitabine and nab-paclitaxel caused tumor regression in xenografts. This phase Ib study evaluated the combination of ipafricept with nab-paclitaxel + gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma (mPDAC).

Patients and Methods::

Dose escalation started with standard dose nab-paclitaxel + gemcitabine and ipafricept (3.5 mg/kg days 1, 15). Because of fragility fractures seen with different anti-Wnt agents, following cohorts had ≥6 patients treated with ipafricept 3 to 5 mg/kg on day 1, and included bone marker monitoring and prophylactic bisphosphonates as indicated. On the basis of preclinical data, sequential dosing was evaluated in cohort 4 (ipafricept day 1 followed nab-paclitaxel + gemcitabine day 3). Objectives included safety, MTD, recommended phase II dose, pharmacokinetics, immunogenicity, pharmacodynamics, and efficacy.

Results::

A total of 26 patients were enrolled, five in cohort 1 and seven each in cohorts 2–4. ipafricept-related adverse events (AEs) of any grade included fatigue, nausea, vomiting, anorexia, and pyrexia. ipafricept-related AEs grade ≥3 included two events of aspartate aminotransferase elevation, and one each of nausea, rash, vomiting, and leucopenia. No dose-limiting toxicities or fragility fractures were observed. Nine patients (34.6%) had partial response, 12 (46.2%) stable disease as best response, with clinical benefit rate of 81%. Median progression-free survival was 5.9 m [95% confidence interval (CI), 3.4–18.4], median overall survival was 9.7 m (95% CI, 7.0–14). The study was terminated by the sponsor due to bone-related toxicity within this therapeutic program and concerns for commercial viability. One patient remains on therapy under compassionate use.

Conclusions::

Ipafricept can be administered with nab-paclitaxel + gemcitabine with reasonable tolerance. Wnt pathway remains a therapeutic target of interest in mPDAC.

16 Mar 2020·Oncology researchQ2 · MEDICINE

Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies

Q2 · MEDICINE

Review

Author: Wang, Wei ; Zhao, Chenghai ; Sun, Yu

Wnt molecules play crucial roles in development and adult homeostasis through their receptors Frizzled proteins (Fzds). Fzds mediate canonical -catenin pathway and various noncanonical -catenin-independent pathways. Aberrant Fzd signaling is involved in many diseases including cancer. Wnt/-catenin is a well-established oncogenic pathway involved in almost every aspect of tumor development. However, Fzd-mediated noncanonical Wnt pathways function as both tumor promoters and tumor suppressors depending on cellular context. Fzd-targeted therapies have proven to be effective on cultured tumor cells, tumor cell xenografts, mouse tumor models, and patient-derived xenografts (PDX). Moreover, Fzd-targeted therapies synergize with chemotherapy in preclinical models. 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.

15 Dec 2017·Clinical cancer research : an official journal of the American Association for Cancer Research

A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors

Article

Author: Dupont, Jakob ; Jimeno, Antonio ; Mendelson, David ; Brachmann, Rainer K. ; Xu, Lu ; Kapoun, Ann M. ; Messersmith, Wells ; Gordon, Michael ; Chugh, Rashmi ; Smith, David C. ; Stagg, Robert ; Uttamsingh, Shailaja

Abstract:

Purpose: Wnt signaling is implicated in tumor cell dedifferentiation and cancer stem cell function. Ipafricept (OMP-54F28) is a first-in-class recombinant fusion protein with the extracellular part of human frizzled 8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands. This trial evaluated ipafricept in patients with solid tumors.Experimental design: A 3+3 design was used; ipafricept was given intravenously every 3 weeks. The objectives were determination of dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy.Results: 26 patients were treated in seven dose-escalation cohorts (0.5, 1, 2.5, 5, 10, 15, and 20 mg/kg). No further dose escalation was pursued as PK modeling indicated that the target efficacious dose was reached at 10 mg/kg, and fragility fractures occurred at 20 mg/kg. Most common related grade 1 and 2 adverse events (AEs; ≥20% of patients) were dysgeusia, decreased appetite, fatigue, and muscle spasms. Ipafricept-related grade 3 TEAEs included hypophosphatemia and weight decrease (1 subject each, 3.8%). Ipafricept half-life was ∼4 days and had low incidence of antidrug antibody formation (7.69%) with no impact on drug exposure. Six patients had β-C-terminal telopeptide (β-CTX) doubling from baseline, which was reversible. PD modulation of Wnt pathway genes in hair follicles occurred ≥2.5 mg/kg. Two desmoid tumor and a germ cell cancer patient experienced stable disease for >6 months.Conclusions: Ipafricept was well tolerated, with RP2D of 15 mg/kg Q3W. Prolonged SD was noted in desmoid tumor and germ cell cancer patients. Clin Cancer Res; 23(24); 7490–7. ©2017 AACR.

News (Medical) associated with Ipafricept

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 Ipafricept

External Link

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D11758	-	-	DB15045

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic hepatocellular carcinoma	Phase 1	United States	-	01 Jan 2014
Platinum-Sensitive Ovarian Carcinoma	Phase 1	United States	-	01 Jan 2014
Pancreatic Ductal Adenocarcinoma	Phase 1	United States	-	01 Nov 2013
Ovarian Cancer	Phase 1	United States	Bayer AG	01 Jun 2012
Prostatic Cancer	Phase 1	United States	Bayer AG	01 Jun 2012

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02050178 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Pancreatic Cancer First line	26	Gemcitabine+nab-paclitaxel+Ipafricept	efdircliqc(hadhcbtrkx) = wfgfxgbapl kgesqhrdbh (itjcfdtqjv, 3.4 - 18.4) View more	Negative	15 Oct 2020
NCT02092363 (Pubmed \| Obstet Gynecol Surv) Manual	Phase 1	Platinum-Sensitive Ovarian Carcinoma	37	paclitaxel+carboplatin+ipafricept	kmlpmvokhj(ywwtwyrrhn) = jdwjlffhco miobdicdvp (olplfebvyt ) View more	Positive	01 Aug 2019
NCT02050178 (ASCO_GI2019)	Phase 1	Pancreatic Cancer	26	Ipafricept + Nab-P/G	gpshaudgea(fwajhdrqut) = included 2 events of AST elevation, and 1 each of nausea, maculopapular rash, vomiting and WBC decrease bttvejbhfk (huukkwyjgp ) View more	Positive	29 Jan 2019
NCT01608867 (Pubmed) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	26	Ipafricept	bebescyuao(llbqbpcbgk) = 15 mg/kg；Q3W myihbwfjeo (rqyqdhzixb ) View more	Positive	15 Dec 2017
Phase 1b clinical studies (AACR2014)	Phase 1	Hepatocellular Carcinoma \| Ovarian Cancer	-	OMP-54F28	iqlsgmwlse(jfspjlfflv) = induction uqwluecesf (phdgfvuosx ) View more	Positive	01 Oct 2014
Phase 1b clinical studies (AACR2014)	Phase 1	Hepatocellular Carcinoma \| Ovarian Cancer	-	OMP-54F28 + Sorafenib		Positive	01 Oct 2014
NCT01608867 (ASCO2014)	Phase 1	HR-positive/HER2-low Solid Tumors	25	OMP-54F28	locisqcebr(xorkvxrtyv) = dzetjmhklm nliqwyamdx (eqkkkurvom ) View more	-	20 May 2014

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