Longkanker: Peptide vaccin - L-BLP25 - tegen uitgezaaide inoperabele niet-klein-cellige longkanker - fase IIIB - effectief. Nieuwe fase III studie moet resultaten bevestigen

10 november 2011: Bij het herzien van kanker-actueel kwam ik onderstaand artikel over een vaccin voor niet-klein-cellige longkanker tegen. Nu blijkt dat een grote fase III studie geopend is met het vaccin in te brengen via liposomen (vetbolletjes) bij niet-klein-cellige longkanker bij Aziatische longkankerpatienten. Klik hier voor het studieprotocol waar als u meer wilt weten informatie kunt inwinnen. Hier het abstract van deze placebo gecontroleerde gerandomiseerde fase III studie. daaronder de resultaten van een eerdere fase III studie met uitstekende resultaten uit 2004.

BMC Cancer. 2011; 11: 430.

Published online 2011 October 7. doi: 10.1186/1471-2407-11-430

PMCID: PMC3203100

INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer

Yi-Long Wu,¹ Keunchil Park,² Ross A Soo,³ Yan Sun,⁴ Karin Tyroller,⁵ David Wages,⁶ Guy Ely, James Chih-Hsin Yang,⁷ and Tony Mok⁸

¹Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China

²Samsung Medical Center, 50, Irwon-Dong, Gangnam-gu, Seoul, 135-710 Korea

³National University Cancer Institute Singapore (NCIS), National University Hospital, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore

⁴Cancer Hospital and Institute Chinese Academy of Medical Sciences, China

⁵Merck KGaA, Darmstadt, Germany

⁶EMD Serono, Rockland, USA

⁷National Taiwan University Hospital Department of Oncology, 4404 Room, 4F, No.1 Chang De St, 100 Taipei, Taiwan

⁸State Key Laboratory of Southern China, The Chinese University of Hong Kong, Sir YK Pau Cancer Center, Prince of Wales Hospital, Hong Kong, China

Corresponding author.

Yi-Long Wu: syylwu@live.cn ; Keunchil Park: kpark@skku.edu ; Ross A Soo: ross_soo@nuhs.edu.sg ; Yan Sun: suny@csco.org.cn ; Karin Tyroller: KARIN.TYROLLER@merck.de ; David Wages: DAVID.WAGES@emdserono.com ; Guy Ely: guy.ely@merck.de ; James Chih-Hsin Yang: chihyang@ntu.edu.tw ; Tony Mok: tony@clo.cuhk.edu.hk

Received May 11, 2011; Accepted October 7, 2011.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population.

Methods/design

The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m²) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 μg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study.

Discussion

The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available.

3 december 2004: bron: Walstreet Journal

7 december 2004: enkele patiënten hebben contact gehad met het bedrijf dat het vaccin uit onderstaand bericht produceert en onderzoekt en dit is hun antwoord.

Dear ......:

I was sent your e-mail to answer. Regarding our phase IIb trial, the results indicated that patients with stage IIIB disease who received the vaccine did considerably better in terms of survival than did patients with the same stage of disease but who did not receive the vaccine. Patients with stage IV disease did not receive as much benefit from the vaccine as those with the earlier stage. Because of these results, we are planning our next trials to include only patients with stage III NSCLC.

As we do not have a compassionate use program, the only way for an individual to receive L-BLP25 is by entering a clinical trial. We are currently planning two trials, a small trial that will probably take place only in Canada, and a large phase III trial that will be conducted internationally, including in Europe. We hope to begin the small trial in the next several months, and the large one toward the end of next year. I realize the timing of these trials is not going to help you in the immediate future, and I’m sorry about that.

There is another company conducting vaccine trials in lung cancer, called Gemvax. I think they are located in Norway. Their web address is inoperabele niet-klein-cellige longkankerpatiënten stadium IIIB, dus met uitzaaiïngen. Dit tonen de onderzoekers aan met een tussenrapportage van een fase IIB trial van 171 mannen en vrouwen met niet-klein-cellige longkanker. De deelnemende patiënten hebben nu reeds de gemiddelde overlevingstijd bereikt die statistisch staat voor uitgezaaide niet operabele longkanker en deze kan aldus het persbericht van Merck alleen maar langer worden omdat nog een aantal van deze mensen bljikbaar in leven is. Er worden echter geen aantallen genoemd van de patiënten die nog in leven zijn Maar is o.i. toch wel een heel mooi bericht.

Wel opvallend dat Merck in samenwerking met Biomare nu komt met een capsule van aminozuren terwijl bv. verschillende klinieken in het buitenland en bv. ook enkele complementair werkende artsen in Nederland al jaren bepaalde aminozuren toedienen aan kankerpatiënten met vaak inderdaad een verlenging van de levensduur. En niet alleen bij longkankerpatiënten. Hier het persbericht zoals we dat kregen toegestuurd van Karel, waarvoor dank. Pas eind 2005 worden er nieuwe trials opgezet zoals een woordvoerder een patiënt die informeerde liet weten: "The Phase IIb study was conducted in Canada and the UK only. The next Phase of clinical testing will not commence until late 2005. Currently there are no trials running that are enrolling patients. Should that change, information will become available on the patient section of our website", Bill Wickson Manager, Public Relations & Special Assistant

-- PRESS RELEASE: Update of BLP25 Liposome Vaccine Phase IIb trial shows stage IIIB --

EDMONTON, Alberta and DARMSTADT, Germany, Dec. 3 /PRNewswire-FirstCall/ - Biomira Inc. (Nasdaq:BIOM) (TSX:BRA) and Merck KGaA of Darmstadt, Germany, announced today that the updated survival analysis of their completed Phase IIb study of the investigational immunotherapy BLP25 Liposome Vaccine (L-BLP25), used in this trial for the treatment of non-small cell lung cancer (NSCLC), showed that a median survival in the pre-stratified subset of locoregional Stage IIIB patients on the vaccine arm has still not been reached. Lung cancer is the leading cause of cancer-related mortality for both sexes in North America. An exploratory survival update of the randomized, open-label Phase IIb trial of L-BLP25 in 171 men and women with NSCLC, whose disease was stable or who had responded to treatment following first-line standard chemotherapy or a combination of standard chemotherapy and radiotherapy was just completed. This analysis showed that in the subset of men and women with locoregional Stage IIIB disease (locally advanced and unresectable) who received L-BLP25, a survival median has not yet been reached 23 months following the enrollment of the last patient into the trial.
"We believe that the results to date are very exciting, and we look forward to presenting the data," said Alex McPherson, MD, PhD, President and CEO of Biomira Inc.
The study's investigators plan to submit the updated survival data from this analysis for presentation at an upcoming scientific meeting and for publication in a peer reviewed medical journal.

"The data are encouraging and support plans for Merck KGaA and its U.S. subsidiary, EMD Pharmaceuticals, to continue the collaborative development of L-BLP25 with Biomira," said Bernhard Ehmer, MD, Vice President and Head of Merck's Oncology Business Area. "In the new year, the companies plan to discuss a Phase III multinational registration trial with regulatory authorities." In preparation for a potential multinational registration trial, Biomira is already scheduling for the manufacture of new vaccine supplies. These supplies will incorporate manufacturing changes intended to secure the future commercial supply of the vaccine. Scheduling these changes now ensures that the resulting pivotal data will be considered representative of the safety and effectiveness of the commercial supply of the vaccine. To assure the successful initiation of a pivotal trial, a comparability plan is now being developed.

L-BLP25
L-BLP25 is a synthetic MUC1 peptide vaccine. L-BLP25 incorporates a 25-amino acid sequence of the MUC1 cancer mucin, encapsulated in a liposomal delivery system. The liposome enhances recognition of the cancer antigen by the immune system and facilitates better delivery. L-BLP25 is designed to induce an immune response to cancer cells.