Presentation on theme: "New therapeutic approaches in lung cancer Dr Marc Lambrechts."— Presentation transcript:
New therapeutic approaches in lung cancer Dr Marc Lambrechts
Anti-cancer strategies for NSCLC today Traditional therapies Modest but significant benefits Chemo-radiotherapy improves survival in advanced NSCLC Adjuvant chemotherapy improves survival in early stage NSCLC Has reached plateau Targeted therapies Addition of targeted therapies to 1 st -line chemotherapy Use of EGFR tyrosine kinase inhibitors in advanced disease Targeted populations Significant side-effects There is a need for new treatment options that prolong survival and improve quality of life in this group of patients
Body’s natural defence mechanism Recognises foreign and harmful agents (e.g. viruses, bacteria, etc) Initiates response to eliminate potential threats The immune system Activates natural immune system Helps body identify cancer cells Boosts immune response against cancer Immunotherapy
Rationale for therapeutic cancer vaccines Echchakir H, et al. Int Immunol 2000;12:537–546 Wei YQ, et al. Immunol Invest 1989;18:1095–1105 Evidence for the ability of the immune system to recognize tumors Wide range of newly identified potential tumor targets Favourable toxicity profile Possible immuno-stimulating effects of existing therapies Preventive cancer vaccines Used BEFORE the disease is established Used to PREVENT the disease Stimulate the immune system to target INFECTIOUS agents Therapeutic cancer vaccines Used AFTER the disease is established Used to TREAT the disease Stimulate the immune system to target CANCER cells
Identifying a vaccine target/antigen Tumor antigens in lung cancer MUC1MAGE-A3GD3 Can prevent anti-tumor immune response MUC1 tumor antigen Suppresses immune cell function Associated with increased risk of disease progression and poor prognosis
MUC1 expression in lung cancer Tumor type MUC1 expression No. of tissues Reference Breast91 %1447Rakha et al (2005) NSCLC99 %231Merck Serono. Data on file Renal cell carcinoma84 %133Langner et al (2004) Colorectal81 %243Baldus et al (2002) Ovarian83 %63Chauhan et al (2006) SCCHN82 %29Croce et al (2001) Nasopharyngeal100 %38Zhong et al (1993) Gastric77 %136Utsunomiya et al (1998) Prostate79 %89DeNardo et al (2005) Pancreatic81 %53Qu et al (2004) Mesothelioma75 %20Saad et al (2005) Multiple myeloma73 %26Cloosen et al (2006) Esophagus32 %53Kijima et al (2001)
59 studies in NSCLC Results 22 studies active 3 agents in Phase III trials BLP25 Liposome Vaccine (START trial) MAGE-A3 (MAGRIT trial) Belagenpumatucel-L (STOP trial) 917 studies with “cancer vaccines” Lung cancer vaccine trials
Phase III therapeutic cancer vaccine trials in NSCLC Antigen –Antigenic MUC1 peptide Vaccine containing a synthetic antigen, designed to stimulate the immune system against cells containing that antigen. BLP25 Liposome Vaccine BLP25 Liposome Vaccine is currently under clinical investigation and has not been approved for use in the US, Europe, Canada, or elsewhere. BLP25 has not been proven to be either safe or effective and any claims of safety and effectiveness can be made only after regulatory review of the data and approval of the labelled claims
Butts C, et al. J Clin Oncol 2005;23:6674–6681; Butts C, et al. J Thorac Oncol 2007;2(Suppl 4):S332-S333. Abstract No: B1-01. Overall survival BLP25 Phase II results: Stage IIIb locoregional patients Most adverse events were disease related and unrelated to the study drug Mild-to-moderate flu-like symptoms and injection site redness (i.e. cough, fatigue, nausea,vomiting, diarrhea) Ten patients have been treated for up to 8.2 years and eight are still being treated Safety results In a subset of patients, BLP25 showed more than a doubling of the median survival time from 13.3 to 30.6 months and a favorable tolerability profile.
Phase III therapeutic cancer vaccine trials in NSCLC Antigen –Purified MAGE-A3 protein Vaccine containing a synthetic antigen, designed to stimulate the immune system against cells containing that antigen. BLP25 Liposome Vaccine MAGE-A3 Immunotherapeutic
MAGE-A3 Phase II results HR = 0.73 (95% CI ) one-sided logrank p = HR = 0.66 (95% CI ) one-sided logrank p = Disease-free survivalOverall survival MAGE-A3 immunotherapeutic showed a trend toward increasing overall and disease-free survival compared to placebo.
Phase III therapeutic cancer vaccine trials in NSCLC Antigen –Tumor cells from four irradiated NSCL cancer cell lines Genetically engineered to inhibit TGF-β2 which plays a role in suppressing the immune system. BLP25 Liposome Vaccine MAGE-A3 Immunotherapeutic Belagenpumatucel-L
Radiographic evidence Pre-therapy Post-therapy Overall survival (n=61, p=0.0186) Belagenpumatucel-L Phase II results Belagenpumatucel-L showed a positive effect on overall survival and tumor response as shown by the radiographic evidence.
Phase III vaccine trials in NSCLC BLP25 Patients with unresectable stage III NSCLC following chemoradiotherapy BLP25 + BSC Placebo + BSC or 1ry Objective OS 1,322 patients MAGE-A3 Resected patients with stage Ib, II or IIIa, MAGE-A3 positive NSCLC MAGE-A3 Placebo or 1ry Objective PFS 2,270 patients Belagenpumatucel-L Patients with Stage IIIa or IIIb/IV NSCLC that respond to 1 st -line therapy Vaccine + BSC Placebo + BSC or 700 patients 1ry Objective PFS + OS START trialMAGRIT trialSTOP trial