Delving into the Latest Updates on Ipafricept with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

Ipafricept (USAN/INN)

+ [2]

Target

Wnt

Mechanism

Wnt ligand inhibitors

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Hepatocellular CarcinomaOvarian CancerPancreatic Cancer+ [2]

Originator Organization

Mereo BioPharma 5, Inc.

Active Organization-

Inactive Organization

Bayer AG

Mereo BioPharma 5, Inc.

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9645812

Source: *****

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

Mereo BioPharma 5, Inc.

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

Mereo BioPharma 5, Inc.

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

Mereo BioPharma 5, Inc.

100 Clinical Results associated with Ipafricept

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100 Translational Medicine associated with Ipafricept

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100 Patents (Medical) associated with Ipafricept

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8

Literatures (Medical) associated with Ipafricept

15 Oct 2020·Clinical 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: Kapoun, Ann M. ; Brachmann, Rainer K. ; O'Neil, Bert ; Stagg, Robert J. ; Denlinger, Crystal S. ; Dotan, Efrat ; Lenz, Heinz-Josef ; Shahda, Safi ; Uttamsingh, Shailaja ; Astsaturov, Igor ; Cardin, Dana B. ; Cohen, Steven J. ; Weekes, Colin ; Messersmith, Wells

AbstractPurpose: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 Research Featuring Preclinical and Clinical Cancer TherapeuticsQ2 · 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.

01 Aug 2019·Gynecologic OncologyQ2 · MEDICINE

A phase 1b dose escalation study of ipafricept (OMP 54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer

Q2 · MEDICINE

Article

Author: Burger, Robert A ; Morgan, Mark A ; Farooki, Azeez ; Moore, Kathleen N ; Brachmann, Rainer Karl ; McMeekin, D Scott ; Gunderson, Camille C ; Stagg, Robert ; Mantia-Smaldone, Gina ; Kapoun, Ann M ; O'Cearbhaill, Roisin E ; Sabbatini, Paul

OBJECTIVESThe WNT pathway is an important oncologic driver of epithelial ovarian cancer (EOC). The first-in-class recombinant fusion protein ipafricept (IPA) blocks Wnt signaling through binding of Wnt ligands. This phase Ib trial was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RPh2) for IPA in combination with taxane and platinum therapy (C/P).METHODSDose escalation started with a standard 3 + 3 design for IPA/C/P with q3w intravenous IPA on Day 1, in cycles 1 to 6 with C (AUC = 5 mg/ml·min) and P (175 mg/m²). For enhanced bone safety the trial was revised to 6-patient cohorts with a q3w regimen of IPA on Day 1 and C/P on Day 3 (IPA → C/P).RESULTS37 patients have been treated; 30 of whom were treated following protocol revision to q3w IPA(D1) → C/P(D3) (2 & 4 mg/kg). IPA-related TEAEs that occurred in ≥15% included: fatigue (40%); nausea (35%); diarrhea and decreased appetite (22%) each; dysgeusia (19%); and vomiting (16.2%). 22% reported ≥1 IPA related TEAE Grade ≥3 the most common of which was neutropenia at 16%. There were no DLTs; the MTD was not reached. The maximum administered dose based on bone safety was 6 mg/kg. The overall response rate (ORR) was 75.7%. Median PFS was 10.3 months (95% CI 8.5-14.2) and OS 33 months (95% CI 23.4-NR).CONCLUSIONSIPA is well tolerated in combination with sequential C/P. ORR, PFS and OS are comparable to historical data but bone toxicity at efficacy doses of this particular Wnt inhibitor limit further development in EOC.

100 Deals associated with Ipafricept

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External Link

KEGG	Wiki	ATC	Drug Bank
D11758	-	-	DB15045

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Platinum-Sensitive Ovarian Carcinoma	Phase 1	US	Mereo BioPharma 5, Inc.	01 Jan 2014
Hepatocellular Carcinoma	Phase 1	-	Bayer AG	-
Hepatocellular Carcinoma	Phase 1	-	Bayer AG	-
Ovarian Cancer	Phase 1	-	Bayer AG	-
Ovarian Cancer	Phase 1	-	Bayer AG	-
Pancreatic Cancer	Phase 1	-	Bayer AG	-
Pancreatic Cancer	Phase 1	-	Bayer AG	-
Prostatic Cancer	Preclinical	US	Bayer AG	01 Jun 2012

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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	(voxuzpeogl) = tjtzvpxkrk acmswprbbd (rtfuxcljoq, 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	(msgfvdhabx) = ocgelprdmf uwomtfbgyf (yndygzxrfs ) View more	Positive	01 Aug 2019
NCT02050178 (ASCO_GI2019)	Phase 1	Pancreatic Cancer	26	Ipafricept + Nab-P/G	(pmbywhcekh) = included 2 events of AST elevation, and 1 each of nausea, maculopapular rash, vomiting and WBC decrease bhuctuenzq (ftikahkmhn ) View more	Positive	29 Jan 2019
NCT01608867 (Pubmed) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	26	Ipafricept	(doyywovqyk) = 15 mg/kg；Q3W krdwovxnon (arykidjwxd ) View more	Positive	15 Dec 2017
AACR2014	Phase 1	Hepatocellular Carcinoma \| Ovarian Cancer	-	OMP-54F28	dvhybisyxw(hzovpipzyq) = induction zyxmhrzuox (kjerwxfdyg ) View more	Positive	01 Oct 2014
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	(zddwyssvzl) = afdbbgtdls srxzkxuryr (mlmrraoqun ) View more	-	20 May 2014