Delving into the Latest Updates on LMB-100 with Synapse

Overview

Basic Info

Drug Type

Fab fragment

Synonyms

anti-MSLN-PE24-cFP

+ [4]

Target

MSLN

Action

inhibitors

Mechanism

MSLN inhibitors(Mesothelin inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Mesothelioma

Inactive Indication

Adenocarcinoma of LungBile Duct NeoplasmsEpithelioid mesothelioma, malignant+ [9]

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization

Selecta Biosciences, Inc.F. Hoffmann-La Roche Ltd.

Inactive Organization

National Cancer InstituteHoffmann-La Roche, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Background:
Cancers that spread into the thin tissue lining your lungs (pleura) cause serious illness. They often recur when removed. These tumors include malignant pleural mesothelioma (MPM), caused by exposure to asbestos and related fibers. Malignant pleural effusions (MPEs) are caused when cancers in other parts of the body spread to the lungs and pleura. Many people diagnosed with pleural tumors survive less than a year.
Objective:
To test the safety of a study drug (LMB-100) in people. LMB-100 may help stop pleural tumors from recurring after surgery.
Eligibility:
People aged 18 years or older diagnosed with MPM or related cancer that has spread into the pleura.
Design:
Participants will undergo screening. They will have a physical exam with blood and urine tests. They will have CT scans. They will have tests that measure the how their heart and lungs function. They will provide a sample of tumor tissue to determine if their tumor expresses a protein called mesothelin.
Participants will undergo standard surgery to maximally remove the plural tumors. Then they will have LMB-100 pumped into their chest. The liquid will rinse the chest wall, diaphragm, heart sac, and surface of the lungs for 90 minutes. Then the liquid will be drained and the surgical incisions closed. The participants will be under anesthesia during this procedure.
Participants will remain in the intensive care unit for a least 48 hours. They will remain in the hospital for up to a week or more until recovered enough to be safely discharged.
Participants will return for regular follow-up visits for 2 years.

Start Date31 Jan 2024

Sponsor / Collaborator

National Cancer Institute

NCT04840615

/ TerminatedPhase 1IIT

Phase I Study of Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma

Background:
Mesothelioma is a type of cancer. It originates in cells that line human body cavities. Most people have advanced disease when they are diagnosed. Researchers want to see if a combination of drugs can help.
Objective:
To find a safe dose of LMB-100 in combination with ipilimumab when LMB-100 is injected into tumors.
Eligibility:
Adults ages 18 and older with malignant pleural or peritoneal mesothelioma, that cannot be cured with surgery and has not responded to standard first-line treatments for mesothelioma.
Design:
Participants will be screened with:
Tumor biopsy or effusion, if needed
Medical history
Physical exam
Blood and urine tests
Imaging scans
Heart and lung function tests
Pregnancy test, if needed
Some screening tests will be repeated during the study.
Participants will get LMB-100 on Days 1 and 4 for up to 2 cycles. Each cycle lasts 21 days. They will stay in the hospital for about 8 days each time they get LMB-100. It will be injected into their tumor with needles.
Participants will get ipilimumab through a tube that is put in a vein. It will be given on Day 2 of the first 2 cycles and Day 1 of the next 2 cycles.
Participants will be assessed for how well they do daily activities. They will give blood and tissue samples for research.
Participants will have a safety visit 4 to 6 weeks after the last dose of the study drugs. Then they will have scans every 6 weeks until their disease gets worse. If their tumor gets bigger, they will have phone, video, or email follow-ups every 12 weeks.
Participants will be on this study for life....

Start Date11 Jun 2021

Sponsor / Collaborator

National Cancer Institute

NCT04027946

/ TerminatedPhase 2IIT

A Phase II Study of LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Background:
Over 230,000 new lung cancer cases are diagnosed every year in the United States (U.S.) About 80% of lung cancers are non- small cell lung cancer (NSCLC). Most people have a more advanced stage of the disease that doesn't respond well to standard treatment. Researchers want to see if a combination of drugs may be able to help.
Objective:
To find out if LMB-100 followed by pembrolizumab can help tumors to shrink in people with NSCLC.
Eligibility:
People ages 18 and older with NSCLC that has not responded to standard therapies
Design:
Participants will be screened with:
Medical history
Physical exam
Tumor sample. If one is not available, they will have a biopsy.
Assessments of ability to perform normal activities
Lung function tests
Blood, heart, and urine tests
Computed tomography (CT) and positron emission tomography (PET). They will lie in a machine that takes pictures of the body.
Participants will take LMB-100 in 21-day cycles for up to 2 cycles. They will take the drug by injection into an arm vein on days 1, 3, and 5 of each cycle. They will stay in the hospital 7-10 days each cycle. Then they will get pembrolizumab by injection into an arm vein every 3 weeks for up to 2 years. They may be able to take pembrolizumab an additional year if their cancer gets worse.
Participants will have repeats of the screening tests throughout the study.
About 30 days and 90 days after they stop treatment, participants will have follow-up visits. Then they will have visits every 6-12 weeks. They will be followed for the rest of their life through phone calls and emails.

Start Date11 Sep 2019

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with LMB-100

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100 Translational Medicine associated with LMB-100

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100 Patents (Medical) associated with LMB-100

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25

Literatures (Medical) associated with LMB-100

29 Nov 2022·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Anti-mesothelin immunotoxin induces mesothelioma eradication, anti-tumor immunity, and the development of tertiary lymphoid structures

Q1 · CROSS-FIELD

Article

Author: Pastan, Ira ; Liu, Xiufen ; Tai, Chin-Hsien ; Liu, Wenlong

LMB-100 is a recombinant immunotoxin composed of a Fab linked to a toxin. It kills cells expressing human mesothelin (hMSLN), which is highly expressed on the surface of mesothelioma and many other cancer cells. Clinically, we observed some patients had delayed responses to an anti-hMSLN immunotoxin treatment, suggesting the induction of anti-tumor immunity. We aimed to develop a mouse model to investigate whether immunotoxin alone can induce anti-tumor immunity and to study the mechanism of this immunity. An immunocompetent transgenic mouse was used to grow mouse mesothelioma AB1 cells expressing hMSLN in the peritoneal cavity. Mice were treated with LMB-100, and mice with complete responses (CRs) were rechallenged with tumor cells to determine whether anti-tumor immunity developed. Changes in gene expression profiles were evaluated by Nanostring, and changes in cytokines and chemokines were checked by protein arrays. The distribution of various immune cells was assessed by immunohistochemistry. Our results show that the mice with tumor reached CRs and developed anti-tumor immunity after LMB-100 treatment alone. The primary response requires CD8 + T cells, CD4 + T cells, and B cells. Transcriptional profiling shows that LMB-100 treatment reshapes the tumor immune microenvironment by upregulating chemotaxis signals. LMB-100 treatment upregulates genes associated with tertiary lymphoid structures (TLS) development and induces TLS formation in tumors. In sum, immunotoxin-mediated cell death induces anti-tumor immunity and the development of TLS, which provides insights into how immunotoxins cause tumor regressions.

01 Jul 2020·Science Translational MedicineQ1 · MEDICINE

Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti–PD-1 antibody in patients with mesothelioma and mouse tumor models

Q1 · MEDICINE

Article

Author: Hassan, Raffit ; Zhang, Jingli ; Jiang, Qun ; Ghafoor, Azam ; Morrow, Betsy ; Thomas, Anish ; Mian, Idrees ; Sengupta, Manjistha ; Ahlman, Mark A. ; Rathkey, Daniel ; Steinberg, Seth M. ; Pastan, Ira ; Alewine, Christine

Mesothelin-targeted immunotoxin LMB-100 with anti–PD-1 antibody enhanced antitumor activity in patients with mesothelioma and mouse tumor models.

15 Feb 2020·Clinical Cancer ResearchQ1 · MEDICINE

Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma

Q1 · MEDICINE

Article

Author: Yuno, Akira ; Hassan, Raffit ; Steinberg, Seth M. ; Alewine, Christine ; Pastan, Ira ; Lee, Min-Jung ; Trepel, Jane B. ; Kindrick, Jessica D. ; Hu, Zishuo I. ; Thomas, Anish ; Ahmad, Mehwish ; Peer, Cody J. ; Figg, William D.

AbstractPurpose:LMB-100 is a recombinant immunotoxin (iTox) consisting of a mesothelin-binding Fab for targeting and a modified Pseudomonas exotoxin A payload. Preclinical studies showed that combining taxanes with iTox results in synergistic antitumor activity. The objectives of this phase I/II study were to determine the MTD of LMB-100 when administered with nanoalbumin bound (nab)-paclitaxel to patients with previously treated advanced pancreatic adenocarcinoma and to assess the objective response rate.Patients and Methods:Patients (n = 20) received fixed-dose nab-paclitaxel (125 mg/m2 on days 1 and 8) with LMB-100 (65 or 100 μg/kg on days 1, 3, and 5) in 21-day cycles for 1–3 cycles.Results:Fourteen patients were treated on the dose escalation and an additional six in the phase II expansion. MTD of 65 μg/kg was established for the combination. Dose-limiting toxicity resulting from capillary leak syndrome (CLS) was seen in two of five patients treated at 100 μg/kg and one of six evaluable phase I patients receiving the MTD. Severity of CLS was associated with increases in apoptotic circulating endothelial cells. LMB-100 exposure was unaffected by anti-LMB-100 antibody formation in five of 13 patients during cycle 2. Seven of 17 evaluable patients experienced >50% decrease in CA 19-9, including three with previous exposure to nab-paclitaxel. One patient developed an objective partial response. Patients with biomarker responses had higher tumor mesothelin expression.Conclusions:Although clinical activity was observed, the combination was not well tolerated and alternative drug combinations with LMB-100 will be pursued.

100 Deals associated with LMB-100

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of Lung	Phase 2	United States	National Cancer Institute	11 Sep 2019
Squamous non-small cell lung cancer	Phase 2	United States	National Cancer Institute	11 Sep 2019
Malignant Mesothelioma of Peritoneum	Phase 2	United States	National Cancer Institute	28 Feb 2018
Mesothelin positive Solid Tumors	Phase 2	United States	National Cancer Institute	03 Aug 2016
Mesothelioma	Phase 2	-	Selecta Biosciences, Inc.	-
Mesothelioma	Phase 2	-	F. Hoffmann-La Roche Ltd.	-
Mesothelioma	Phase 2	United States	National Cancer Institute	-
Pancreatic Cancer	Phase 2	United States	National Cancer Institute	-
Mesothelin positive Solid Tumors	Phase 1	United States	National Cancer Institute	03 Aug 2016
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 1	United States	National Cancer Institute	03 Aug 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04840615 (CTgov)	Phase 1	Mesothelioma, Malignant \| Malignant Mesothelioma of Peritoneum	2	LMB-100 (All Participants in Dose Level 1: 400 mcg LMB-100)	bbuongujrx(rxzbyvdozc) = evuchctuwx bleaqqzuqs (ingnmefkna, vicspcaweq - eoijnsrilt)	-	02 Feb 2024
NCT04840615 (CTgov)	Phase 1		2	LMB-100 (Dose Level 1: 400 mcg LMB-100)	whwsrduaep(bknhaatyvc) = brfuieplfl xbhkgndagm (qtetupuppz, vpvweqidnx - mpnfnnjrvd) View more	-	02 Feb 2024
NCT02798536 (CTgov)	Phase 1	Mesothelioma, Malignant	21	LMB-100+Nab-Paclitaxel (All Participants)	tztgaxxict(fjfebextbp) = lifscmyzbu nawjxnaxey (jvzdmyadpv, kulfxbdyoz - jjzicfzege) View more	-	23 Aug 2022
NCT02798536 (CTgov)	Phase 1	Mesothelioma, Malignant	21	LMB-100 (Dose Level -1: 140mcg LMB-100)	(nelxdxjlks) = mggslvyiyg osklmeugvp (emtjmhgnpu, ovnswzaitn - achlvrfjnb) View more	-	23 Aug 2022
NCT03644550 (CTgov)	Phase 2	Mesothelioma, Malignant \| Malignant Mesothelioma of Peritoneum	18	LMB-100+pembrolizumab	(woypdphdib) = fucgzzybst pbnlpurqcx (lwqqyreqsg, rylghgevls - zmgwztwddq) View more	-	02 Dec 2021
NCT04034238 (ASCO_GI 12021 \| ASCO_GI 22021) Manual	Phase 1	Advanced Bile Duct Carcinoma	13	tofacitinib+LMB-100	(buxmpxwvex) = Of the 8 patients who received two cycles of treatment at MTD, 4 met prespecified criteria for ADA prevention, and 2 patients who went on ~ receive cycle 3 had detectable LMB-100 plasma drug levels after administration snzxmfpjkp (sijtjyzfqh ) View more	Negative	22 Jan 2021
NCT02810418 (Pubmed \| Clin Cancer Res) Manual	Phase 1/2	Advanced Pancreatic Adenocarcinoma	20	Albumin-Bound Paclitaxel+LMB-100	(ykdmzlhusa) = rljfnbdios lxaapykjrs (djgeoaykbv ) View more	Negative	15 Feb 2020
NCT03644550 (WCLC2019)	Phase 2	Mesothelioma	18	LMB-100	(elnzaywmui) = mobetitdag xbsuvqiwjr (egnibpyrzd ) View more	-	09 Sep 2019
SITC2015	Phase 1	Neoplasms human mesothelin	-	RG7787 + anti CTLA4	twsdqkrrzf(fhbpnmaeht) = kacscaizyq ngpiooevsv (cqwlfipxcy )	Positive	04 Nov 2015
SITC2015	Phase 1	Neoplasms human mesothelin	-	anti CTLA4	twsdqkrrzf(fhbpnmaeht) = bkbaschfll ngpiooevsv (cqwlfipxcy )	Positive	04 Nov 2015

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