Delving into the Latest Updates on CV-9202 with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine, mRNA vaccine

Synonyms

+ [1]

Target

5T4 x MAGEC1 x MAGEC2 x MUC1 x NY-ESO-1 x survivin

Mechanism

5T4 inhibitors(Trophoblast glycoprotein inhibitors), MAGEC1 antagonists(MAGE family member C1 antagonists), MAGEC2 antagonists(MAGE family member C2 antagonists)

+ [3]

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication

metastatic non-small cell lung cancer

Originator Organization

Cancer Research Institute

Active Organization

Ludwig Institute for Cancer Research Ltd.C.H. Boehringer Sohn AG & Co. KG

Cancer Research Institute

Inactive Organization

CureVac NV

PharmaJet, Inc.

CureVac SE

+ [2]

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 1038074778

Sequence Code 1038074779

Sequence Code 1038074782

Sequence Code 1038074781

Sequence Code 1038074783

Sequence Code 1038074780

This is an open-label, multicenter, 2-arm study to evaluate the safety and preliminary efficacy of the addition of a vaccine therapy to 1 or 2 checkpoint inhibitors for NSCLC.
Arm A: messenger ribonucleic acid (mRNA) Vaccine [BI 1361849 (formerly CV9202)] + anti-programmed death ligand 1 (PD-L1) antibody [durvalumab]
Arm B: messenger ribonucleic acid (mRNA) Vaccine [BI 1361849] + anti-programmed death ligand 1 (PD-L1) [durvalumab] + anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody [tremelimumab]
The run-in evaluation phase is followed by an expansion phase in which the cohort is expanded to 20 subjects (inclusive of subjects from the run-in).

Start Date20 Dec 2017

Sponsor / Collaborator

Ludwig Institute for Cancer Research Ltd.

[+5]

EUCTR2014-004959-30-BE

/ Not yet recruitingPhase 2

A randomised, double-blind phase II trial to determine efficacy, safety and immunogenicity of BI 1361849 (CV9202) maintenance vaccination therapy versus placebo given intradermally in patients with inoperable locally advanced NSCLC after definitive concurrent chemoradiation (CRT) therapy - Phase II study of BI 1361849 (CV9202) vs. placebo after definitive CRT

Start Date11 May 2016

Sponsor / Collaborator

SCS Boehringer Ingelheim Comm.V

NCT01915524

/ TerminatedPhase 1

An Exploratory, Open-label Phase Ib Study of RNActive®-Derived Cancer Vaccine and Local Radiation as Consolidation and Maintenance Treatment in Patients With Stage IV NSCLC and a Response or Stable Disease After First-line Chemotherapy or Therapy With an EGFR Tyrosine Kinase Inhibitor

The purpose of this study is to determine whether the new RNActive derived lung cancer vaccine CV9202 in combination with local radiation therapy is safe, tolerable and immunogenic for the consolidation and maintenance treatment of stage IV non small cell lung cancer (NSCLC) after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor.

Start Date01 Apr 2013

Sponsor / Collaborator

CureVac NV

100 Clinical Results associated with CV-9202

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100 Translational Medicine associated with CV-9202

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100 Patents (Medical) associated with CV-9202

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2

Literatures (Medical) associated with CV-9202

01 Dec 2019·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer

Q2 · MEDICINE

ArticleOA

Author: Fotin-Mleczek, Mariola ; Wehler, Thomas ; Sebastian, Martin ; Koch, Sven D ; Griesinger, Frank ; Gnad-Vogt, Ulrike ; Alt, Jürgen ; Geißler, Michael ; Schröder, Andreas ; Stosnach, Claudia ; Seibel, Tobias ; Pless, Miklos ; Doener, Fatma ; Weiss, Christian ; Muth, Anke ; Papachristofilou, Alexandros ; Cathomas, Richard ; Scheel, Birgit ; Bischoff, Helge ; Hipp, Madeleine M ; Hong, Henoch S ; Kallen, Karl-Josef ; Zippelius, Alfred ; Klinkhardt, Ute ; Früh, Martin ; Pall, Georg ; Hilbe, Wolfgang

BACKGROUNDPreclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses.METHODSWe describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61).RESULTSStudy treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions.CONCLUSIONThe results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT01915524 .

01 Dec 2014·BMC CancerQ2 · MEDICINE

Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive®) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer

Q2 · MEDICINE

ArticleOA

Author: Karl-Josef Kallen ; Richard Cathomas ; Mariola Fotin-Mleczek ; Regina Heidenreich ; Martin Sebastian ; Martin Früh ; Ulrike Gnad-Vogt ; Alfred Zippelius ; Sven D Koch ; Thomas Wehler ; Wolfgang Hilbe ; Alexandros Papachristofilou ; Birgit Scheel ; Gerd Rippin ; Christian Weiss

BACKGROUNDAdvanced non-small cell lung cancer (NSCLC) represents a significant unmet medical need. Despite advances with targeted therapies in a small subset of patients, fewer than 20% of patients survive for more than two years after diagnosis. Cancer vaccines are a promising therapeutic approach that offers the potential for durable responses through the engagement of the patient's own immune system. CV9202 is a self-adjuvanting mRNA vaccine that targets six antigens commonly expressed in NSCLC (NY-ESO-1, MAGEC1, MAGEC2, 5 T4, survivin, and MUC1).METHODS/DESIGNThe trial will assess the safety and tolerability of CV9202 vaccination combined with local radiation designed to enhance immune responses and will include patients with stage IV NSCLC and a response or stable disease after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor. Three histological and molecular subtypes of NSCLC will be investigated (squamous and non-squamous cell with/without EGFR mutations). All patients will receive two initial vaccinations with CV9202 prior to local radiotherapy (5 GY per day for four successive days) followed by further vaccinations until disease progression. The primary endpoint of the study is the number of patients experiencing Grade >3 treatment-related adverse events. Pharmacodynamic analyses include the assessment of immune responses to the antigens encoded by CV9202 and others not included in the panel (antigen spreading) and standard efficacy assessments.DISCUSSIONRNActive self-adjuvanted mRNA vaccines offer the potential for simultaneously inducing immune responses to a wide panel of antigens commonly expressed in tumors. This trial will assess the feasibility of this approach in combination with local radiotherapy in NSCLC patients.TRIAL REGISTRATIONClinicaltrials.gov: NCT01915524/EudraCT No.: 2012-004230-41.

1

News (Medical) associated with CV-9202

17 Aug 2021

·www.biospace.com

Boehringer, CureVac Terminate Lung Cancer Project on Poor Performance

Andreas Arnold/picture alliance via Getty Images Tübingen-based biopharmaceutical firm CureVac has revealed in its latest financial report that its lung cancer program with German biotechnology company Boehringer Ingelheim has been terminated. The move ends a €500m exclusive treatment exploration and development partnership which both parties signed seven years ago (2014). The collaboration focused on the viability of using CureVac's CV9202 therapeutic mRNA vaccine with afatinib in patients who have been diagnosed with advanced or metastatic epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). It was also being tested in combination with chemo-radiation therapy in patients who have unresectable stage III NSCLC. However, in a brief statement hidden among its financials, CureVac said that it had terminated the agreement in June, with the process expected to be finalized by November 2021. The company said that despite the decision to discontinue their partnership on the project, the two firms will still continue to find ways to collaborate on other ways to use CureVac's RNA technology for other potential treatment purposes. While it did not explicitly state a reason, CureVac added that they were working with a "legacy program" that used an older protamine formulation, which was being developed seven years ago. It also stated that it is continuing its Phase I of II clinical trial for the potential of BI1361849 for NSCLC. CureVac did not provide any further details about the termination or any other plans moving forward. However, what is noticeable is that it comes just two months after it reported weak efficacy results of only 47% for an mRNA vaccine against COVID-19. Other rival medications had an efficacy of more than 90%. Industry observers had been setting their sights on the vaccine as it was thought to last longer and cost less. "While we were hoping for a stronger interim outcome, we recognize that demonstrating high efficacy in this unprecedented broad diversity of variants is challenging," said CureVac's Chief Executive Officer, Dr. Franz-Werner Haas, in a statement. "In addition, the variant-rich environment underlines the importance of developing next-generation vaccines as new virus variants continue to emerge." The CureVac-Boehringer trial involved 40,000 participants, with 75% based in Latin America and 25% in Europe. The 47% who showed efficacy represented around 46 cases from the vaccinated group and 88 cases in the placebo group. As part of that deal, CureVac received €35 million and was set to achieve milestone payments of as much as €430 million plus royalties from future sales. Boehringer has yet to issue an official statement about this revelation.

VaccineRadiation TherapyFinancial StatementCollaboratemRNA

100 Deals associated with CV-9202

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 2	-	Cancer Research Institute	-
Non-Small Cell Lung Cancer	Phase 2	-	C.H. Boehringer Sohn AG & Co. KG	-
Non-Small Cell Lung Cancer	Phase 2	-	Ludwig Institute for Cancer Research Ltd.	-
metastatic non-small cell lung cancer	Preclinical	US	MedImmune LLC	20 Dec 2017
metastatic non-small cell lung cancer	Preclinical	US	CureVac NV	20 Dec 2017
metastatic non-small cell lung cancer	Preclinical	US	PharmaJet, Inc.	20 Dec 2017
metastatic non-small cell lung cancer	Preclinical	US	MedImmune LLC	20 Dec 2017
metastatic non-small cell lung cancer	Preclinical	US	PharmaJet, Inc.	20 Dec 2017
metastatic non-small cell lung cancer	Preclinical	US	CureVac NV	20 Dec 2017
Non-Small Cell Lung Cancer	Preclinical	DE	CureVac SE	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2024 Manual	Phase 1	Non-Small Cell Lung Cancer	57	BI1361849 + durvalumab	(pewpdqngkc) = szsvvmoftd ezdfkwpsvw (azrhzfusma ) View more	Positive	05 Apr 2024
				BI1361849 + durvalumab + tremelimumab	(pewpdqngkc) = sjtbtgyrrb ezdfkwpsvw (azrhzfusma ) View more
NCT03164772 (CTgov)	Phase 1/2	metastatic non-small cell lung cancer	61	PharmaJet Tropis® device+Durvalumab+BI 1361849 (Arm A: BI 1361849 mRNA Vaccine + Durvalumab)	(wkqjfhzfjl) = bvtxsbcfya xtfhltpamy (yehnbnuzhs, ynwfdrshnq - rcdjbsvrrz) View more	-	27 Sep 2022
				PharmaJet Tropis® device+Tremelimumab+Durvalumab+BI 1361849 (Arm B: BI 1361849 mRNA Vaccine + Durvalumab + Tremelimumab)	(wkqjfhzfjl) = dfhbsqeirg xtfhltpamy (yehnbnuzhs, ztcvppapfw - aczukaiehb) View more
NCT01915524 (Pubmed \| J Immunother Cancer) Manual	Phase 1	metastatic non-small cell lung cancer	26	local radiation+BI1361849	(lsdxwqtwcd) = Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia) becjujshng (ttkdzyjygv ) View more	Positive	08 Feb 2019