Stimuvax (tecemotide) / EMD Serono, Ono Pharma, Pfizer - LARVOL DELTA

Tumor Necrosis Factor-related Weak Inducer of Apoptosis (TWEAK) - A Potential Biomarker for Predicting Response and Long-Term Outcomes in Early Breast Cancer Patients (SABCS 2025) - "Background: Baseline plasma levels of Tumor Necrosis Factor-related Weak Inducer of Apoptosis (TWEAK), Vascular endothelial growth factor A (VEGF-A), Programmed cell death 1 ligand 2 (PD-L2), and Osteoprotegerin (OPG) were analyzed for their predictive value in women with early-stage HER2-negative breast cancer who received neoadjuvant chemotherapy or endocrine therapy, and were randomized 1:1 to additional MUC1-based immunotherapy (tecemotide, L-BLP25). Plasma levels of the biomarkers were assessed in 314 patients from the prospective, randomized, open-label, 2-arm phase-II ABCSG-34 trial before neoadjuvant treatment... Low baseline TWEAK levels predicted significantly better pathological response measured by RCB to MUC1-based vaccination. Although long-term outcomes did not reach statistical significance, clinically meaningful benefits in iDFS, OS, and DRFS were seen in patients with low TWEAK baseline levels. These findings support TWEAK as a potential predictive..."

Biomarker • Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC1 • PD-1 • PD-L2 • TNFRSF11B • TNFSF12

Immune activation of tumor cells and microenvironment as assessed by PD-L1 expression and interferon gamma signaling predict long term disease-free and overall survival: Results of the prospective randomized neoadjuvant ABCSG 34 trial (SABCS 2024) - "Patients were randomized 1:1 to receive either Standard of Care (SoC) or SoC plus the MUC1-based antitumor vaccine tecemotide... The results of this study indicate that in the ABCSG 34 trial, PD-L1 positivity as determined by IC and CPS was able to predict better DRFS and OS. However, in patients with residual tumor, an increase in CPS during treatment was associated with decreased OS - a result that needs to be interpreted with caution, since no "post treatment sample" can be accessed in cases of pCR. In addition, IRF1 expression both in tumor cells and TILs predicted an improved IDFS and DRFS."

Clinical • IO biomarker • Tumor cell • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Triple Negative Breast Cancer • HER-2 • IFNG • IRF1 • MUC1 • PD-L1 • STAT1

Vaccination with MUC-1-targeting tecemotide improves Survival of patients receiving neo-adjuvant chemotherapy for early breast cancer: Results from the Prospective Randomized ABCSG 34 Trial. (SABCS 2024) - "Postmenopausal women with luminal A tumors received letrozole 2.5mg od for 24 weeks as SoC. TNBC patients and patients with luminal B tumors, in whom chemotherapy was considered to be SoC, received 4 x epirubicin/cyclophosphamide and 4 x docetaxel q3w... Tecemotide, when given concomitantly with neoadjuvant SoC systemic therapy, profoundly improved IDFS, DRFS and OS in a follow-up analysis of this prospective Phase II trial. The improved long-term outcome was particularly evident in patients whose tumors expressed high levels of MUC1. While long-term outcome is an exploratory objective, this is the first study in which a therapeutic cancer vaccine has resulted in a statistically significant and substantial long-term survival benefit in breast cancer patients."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1 • PD-L1

Monocyte subsets in breast cancer patients under treatment with aromatase inhibitor and mucin-1 cancer vaccine. (PubMed, J Transl Med) - "This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • MUC1

Addition of the MUC-1 vaccine tecemotide to neoadjuvant systemic therapy for patients with early breast cancer: Survival results from the prospective randomized ABCSG 34 trial. (ASCO 2024) - P2 | " 400 patients with HER2- early BC were randomized 1:1 to receive preoperative SoC treatment with or without tecemotide: Postmenopausal women with luminal A tumors received 6 months of letrozole as SoC, while postmenopausal patients with TNBC, luminal B tumors, in whom chemotherapy was considered to be SoC, and all premenopausal patients received 4 x EC and 4 x Docetaxel q3w. The MUC-1 vaccine tecemotide, when added to standard neoadjuvant systemic therapy, markedly improved DRFS and OS. Despite the exploratory nature of this observation, this is the first significant and profound long-term survival benefit of an anti-cancer vaccine in breast cancer patients reported to date. Additional studies are needed to understand in more detail the underlying mechanisms, and the optimal use of cancer vaccines in breast cancer treatment."

Clinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • MUC1

Optimal Integration of Radiotherapy, TKIs and I/O (IASLC-WCLC 2019) - "...The PACIFIC trial (PD-L1 inhibitor Durvalumab vs placebo, unresectable stage III NSCLC who did not progress following concurrent platinum-based chemo-radiotherapy) showed a major improvement in 2-year PFS and OS, which holds promise for an improved cure rate (7). Even the use of Pembrolizumab (anti-PD-1 agent) is under investigation in a series of trials. A number of studies (e.g. INSPIRE study) investigated the role of Tecemotide (anti-tumor vaccine inducing a specific immune response against MUC-1, glycoprotein overexpressed in NSCLC) (8) in Stage III NSCLC...Some attention should also be paid to those trials introducing anti-PD-1 agents before chemo-radiation, as neo-adjuvant: this innovative approach could be promising, by integrating radio-chemotherapy in a tumor micro-environment already modified by immunomodulators, and with a subsequent consolidation phase. When using anti-PD-L1 agents in this setting, PD-L1 expression levels would probably be necessary to..."

IO biomarker • PD(L)-1 Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Implications for Routine Practice (IASLC-WCLC 2018) - "...3 We now have safety data for stage III patients with nivolumab given concurrently with thoracic chemoradiotherapy, followed by consolidation nivolumab...6 Treating brain melanoma metastases with radiosurgery concurrent with ipilimumab in 57 patients, Mortier found toxicity to be as expected for immunotherapy alone 7 , while a similar study by the same group found toxicity was not increased beyond that for pembrolizumab alone...Prior to CPI entering the clinic, in the START trial stage III patients treated with consolidation tecemotide (liposomal MUC1) vaccine following concurrent chemoradiation showed a 10 month survival advantage not seen in those who had received sequential chemoradiotherapy...Sequential concurrent chemoradiation in stage III NSCLC followed by durvalumab is highly effective. Emerging data suggest that radiotherapy may enhance the effectiveness of immunotherapy in stage IV disease but further randomised data are required. "

Melanoma • Non Small Cell Lung Cancer

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results. (ASCO-GI 2019) - P2; "Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome."

Clinical • IO Biomarker • P2 data

Survival after secondary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (CELIM, FIRE-3). (ASCO-GI 2019) - P2, P3; "...L-BLP25 as antigen-specific cancer vaccine targeting mucin 1 (MUC1) was recently evaluated as adjuvant therapy in mCRC pts after R0/R1 LLD resection (LICC trial, NCT01462513)... Secondary resected pts of LICC, CELIM and FIRE-3 showed impressive median OS with better OS for LICC and a younger patient cohort. The established tight LICC surveillance program after surgery might have had a positive impact on survival."

Survival after secondary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (CELIM, FIRE-3). (ASCO 2019) - P2, P3; "...L-BLP25 as antigen-specific cancer vaccine targeting mucin 1 (MUC1) was recently evaluated as adjuvant therapy in mCRC pts after R0/R1 LLD resection (LICC trial, NCT01462513)... Secondary resected pts of LICC, CELIM and FIRE-3 showed impressive median OS with better OS for LICC and a younger patient cohort. The established tight LICC surveillance program after surgery might have had a positive impact on survival. Clinical trial information: LICC: NCT01462513; FIRE-3: NCT00433927; CELIM: NCT00153998."

Survival after primary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (FFCD ACHBTH AURC 9002 trial and EORTC Intergroup trial 40983). (ASCO 2019) - P2, P3; "...LICC pts received the adjuvant antigen-specific cancer vaccine tecemotide (L-BLP25) or placebo after primary LLD resection for up to 2 years. The FFCD trial compared postoperative 5-FU/leucovorin and the EORTC trial perioperative FOLFOX versus surgery alone... Despite unfavorable disease characteristic in LICC compared with the earlier EORTC and FFCD studies, primary liver resection without adjuvant chemotherapy led to surprisingly good survival outcomes. Improvements in imaging-based pt selection and liver resection techniques might in part explain our finding. Surgery alone appears to be an option for selected pts with resectable LLD."

Neoadjuvant immunotherapy with androgen deprivation therapy (ADT) prior to radiation in prostate cancer: Impact on multiparametric prostate MRI and immune responses (AACR 2017) - P2; "... Treatment-naïve high-risk (Gleason 8-10, PSA>20, or stage T3) prostate cancer patients (pts) were randomized to standard ADT+Radiation + an immunotherapy targeting MUC1 (tecemotide, aka L-BLP25) in this trial (NCT01496131)...Immunotherapy included low dose (300 mg/m2, maximum 600 mg) pre-treatment cyclophosphamide for regulatory T-cell depletion... Based on assessments by erMRI, pts who received ADT+immunotherapy had greater improvements in ADC than pts receiving ADT alone. Given that ADC improvements are associated with decreased tumor density, this suggests a possible greater anti-tumor effect of the ADT-immunotherapy combination vs. ADT alone."

Clinical • Late-breaking abstract • Biosimilar • Genito-urinary Cancer • Oncology • Prostate Cancer

Changes in multiparametric prostate MRI and immune subsets in patients (Pts) receiving neoadjuvant immunotherapy and androgen deprivation therapy (ADT) prior to radiation. (ASCO-GU 2017) - P2; "... Untreatedpts with high-risk prostate cancer were randomized in a trial (NCT01496131) of standard ADT+Radiation + an immunotherapy targeting MUC1 (tecemotide, aka L-BLP25)... Pts who received immunotherapy+ADT for 2 months had greater improvements in ADC values on erMRI, consistent with decreased tumor density, relative to pts receiving ADT alone. Corresponding increases in activated CD8+ T-cells and decreases in MDSCs were seen in pts receiving vaccine+ADT. These preliminary findings suggest that ADC on MRI may be useful in assessing immunologic impact."

Biomarker • Clinical • Myeloid-derived suppressor cells • Prostate Cancer

Liposomal formulations for lung cancer treatment in the last two decades: a systematic review. (PubMed, J Cancer Res Clin Oncol) - "This systematic review (registration number CRD42021246587) demonstrates that liposomal formulations are promising alternatives to overcome limitations of traditional cancer therapy. However, larger, longer, randomized and double-blinded clinical trials, selecting their patients' cohort considering more responsive subgroups would be beneficial to strengthen the scientific and clinical evidence of the results herein reported."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. (PubMed, Cochrane Database Syst Rev) - "The immunological interventions were active immunotherapy Bacillus Calmette-Guérin (BCG) adoptive cell transfer (i.e. transfer factor (TF), tumour-infiltrating lymphocytes (TIL), dendritic cell/cytokine-induced killer (DC/CIK), antigen-specific cancer vaccines (melanoma-associated antigen 3 (MAGE-A3) and L-BLP25), and targeted natural killer (NK) cells...Two trials provided health-related quality of life results with contradicting results.  AUTHORS' Based on this updated review, the current literature does not provide evidence that suggests a survival benefit from adding immunotherapy (excluding checkpoint inhibitors) to conventional curative surgery or radiotherapy, for people with localised NSCLC (stages I to III). Several ongoing trials with immune checkpoints inhibitors (PD-1/PD-L1) might bring new insights into the role of immunotherapy for people with stages I to III NSCLC."

Checkpoint inhibition • Journal • Review • Immune Modulation • Immunology • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MAGEA3

Survival after secondary liver resection in metastatic colorectal cancer: Comparing data of three prospective randomized European trials (LICC, CELIM, FIRE-3). (PubMed, Int J Cancer) - "The objective of this analysis was to compare these favorable outcome data with recent results from the LICC trial investigating the antigen-specific cancer vaccine tecemotide (L-BLP-25) as adjuvant therapy in mCRC patients with LLD after R0/R1 resection...Secondarily resected patients of LICC, CELIM and FIRE-3 showed an impressive median survival with a tendency for improved survival for patients in the LICC trial. A younger patient cohort but also more selective surgery, improved resection techniques, deep responses and a close surveillance program after surgery in the LICC trial may have had a positive impact on survival."

Clinical • Journal • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results. (ASCO-GI 2019) - P2; "The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome."

Clinical • IO Biomarker • P2 data

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results. (ASCO 2019) - P2; "Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513"

Clinical • IO biomarker • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results. (ASCO-GI 2019) - P2; "Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome."

Clinical • IO biomarker • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Neuroendocrine Tumor • Oncology

Survival after secondary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (CELIM, FIRE-3). (ASCO-GI 2019) - P2, P3; "...L-BLP25 as antigen-specific cancer vaccine targeting mucin 1 (MUC1) was recently evaluated as adjuvant therapy in mCRC pts after R0/R1 LLD resection (LICC trial, NCT01462513)... Secondary resected pts of LICC, CELIM and FIRE-3 showed impressive median OS with better OS for LICC and a younger patient cohort. The established tight LICC surveillance program after surgery might have had a positive impact on survival."

E6508: Phase II Study of Immunotherapy with Tecemotide and Bevacizumab after Chemoradiation inUnresectable Stage III NS-NSCLC (IASLC-WCLC 2018) - "Method Subjects with stage III NS- NSCLC suitable for definitive CRT received carboplatin(C) AUC 2 + paclitaxel(P) 45 mg/m2 weekly + 66 Gy/33fx/6.5wk and consolidation C AUC 6 + P 225 mg/m2 q21 days x 2. Conclusion This cooperative group trial met its endpoint, demonstrating tolerability of tecemotide and bevacizumab after CRT and consolidation in NS-NSCLC pts. In this select group of patients, therapy with tecemotide and bevacizumab was associated with encouraging PFS and OS. "

P2 data • Non Small Cell Lung Cancer

Novel Vaccine Combos Represent a Promising Treatment Approach in Breast Cancer (OncLive) - "The future of therapeutic vaccines in breast cancer will be dependent on their use in combination with standard anticancer drugs, checkpoint antagonists, and distinct checkpoint inhibitors, Leisha A. Emens, MD, PhD, said in a presentation during the 20th Annual International Congress on the Future of Breast Cancer East. Vaccine trials have historically not had much success in breast cancer, and research had been slowed by the advent of checkpoint inhibitors, said Emens...during the meeting, which was hosted by the Physicians' Education Resource (PER), LLC."

Media quote

[VIRTUAL] Immunotherapy as a second-line or later treatment modality for advanced non-small cell lung cancer: A review of safety and efficacy (ASHP 2020) - "The eligible trials studied the following therapies: nivolumab (3 trials), pembrolizumab (1 trial), durvalumab (2 trials), atezolizumab (2 trials), avelumab (1 trial), PPV (3 trials), and tecemotide (2 trials). Recent evidence shows durability and limited toxicity of immune-based therapies in the treatment of advanced NSCLC. The majority of research has identified PD-1/PD-L1 immune-checkpoint inhibitors exhibiting favorable toxicity when compared to standard treatment. These modalities have also shown efficacy in NSCLC patients who have failed first-line treatment."

Clinical • Review • Immune Modulation • Inflammation • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MUC1

Conventional versus reverse sequence of neoadjuvant epirubicin/cyclophosphamide and docetaxel: sequencing results from ABCSG-34. (PubMed, Br J Cancer) - "Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option."

Clinical • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2 • MUC1

BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - P2; N=70; Completed; Sponsor: ECOG-ACRIN Cancer Research Group; Active, not recruiting ➔ Completed

Clinical • Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor