DCVax-L (autologous dendritic cell vaccine leaded with autologous tumor cell lysate) / Northwest Biotherap - LARVOL DELTA

Immunotherapy in Glioblastoma: An Overview of Current Status. (PubMed, Clin Pharmacol) - "Immune checkpoint inhibitors (ICIs), including nivolumab and pembrolizumab, have shown benefit in several cancers and are being studied in GB, with ongoing efforts to address the tumor's immunosuppressive environment...Cancer vaccines, especially dendritic cell-based platforms like DCVax-L, have shown promising survival outcomes in clinical trials...In addition, combination strategies involving ICIs, CAR T-cells, vaccines, and oncolytic viruses are being developed to enhance immune response. This review outlines current immunotherapy approaches in GB, focusing on their mechanisms, clinical development, and future directions."

IO biomarker • Journal • Review • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

The challenges and clinical landscape of glioblastoma immunotherapy. (PubMed, CNS Oncol) - "Glioblastoma is associated with a dismal prognosis with the standard of care involving surgery, radiation therapy and temozolomide chemotherapy...To date, the DCVax-L vaccine is the only immunotherapy shown to have statistically significant increased median survival compared with standard-of-care in a Phase III trial: 19.3 months versus 16.5 months. However, this trial used an external control group to compare with the intervention which limits its quality of evidence. In conclusion, glioblastoma immunotherapy requires further investigation to determine its significance in improving disease survival."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Clinical and translational advances in primary brain tumor therapy with a focus on glioblastoma-A comprehensive review of the literature. (PubMed, World Neurosurg X) - "Phase 3 trials indicate the efficacy of DCVax-L in improving survival rates and depatux-m in prolonging progression-free survival. These findings emphasize the importance of personalized treatment approaches and continued exploration of targeted therapies, immunotherapies, and tumor biology understanding in shaping the future of glioblastoma treatment."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Infectious Disease • Oncology • Solid Tumor

Immunotherapeutic Advances in Glioma Management: The Rise of Vaccine-Based Approaches (EANO 2024) - "For example, the IMA950 peptide vaccine resulted in progression-free survival rates of 74% at 6 months and 31% at 9 months in newly diagnosed GBM patients. Similarly, the SurVaxM peptide vaccine led to 95.2% of patients remaining progression-free at 6 months, with an average progression-free survival of 11.4 months and an overall survival of 25.9 months...Dendritic cell vaccines, such as DCVax-L and α-type-1 DC vaccines, demonstrated improvements in overall survival in GBM patients, with long-term benefits observed in patients with a methylated MGMT promoter... Glioma vaccines show promise in stimulating immune responses against tumours, offering potential benefits alongside standard treatments. Challenges in assessing vaccine efficacy and addressing treatment-related adverse effects emphasise the need for further research and clinical trials. Challenges like tumour heterogeneity and immune evasion persist, but advances in genetic engineering and immunotherapy offer hope..."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CSF2

Updates for newly diagnosed and recurrent glioblastoma: a review of recent clinical trials. (PubMed, Curr Opin Neurol) - "Although progress to improve outcomes for GBM patients has been modest, multiple novel strategies utilizing combination therapies, focused ultrasound to improve drug delivery, and novel immunotherapies are underway."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Tumor regression following autologous tumor lysate-loaded dendritic cell vaccination immunotherapy: illustrative case. (PubMed, J Neurosurg Case Lessons) - "The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease. https://thejns.org/doi/10.3171/CASE24112."

IO biomarker • Journal • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Northwest Biotherapeutics Announces That A Marketing Authorization Application Has Been Submitted To The UK MHRA For DCVax-L For Glioblastoma (PRNewswire) - P3 | N=348 | NCT00045968 | Sponsor: Northwest Biotherapeutics | "Northwest Biotherapeutics...announced today that a Marketing Authorization Application (MAA) was submitted yesterday to the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK for DCVax^®-L for glioblastoma brain cancer...The MAA seeks approval for commercialization of DCVax-L for both newly diagnosed and recurrent glioblastoma (GBM). The application also requests to be considered under the MHRA's rapid 150-day review pathway, which the agency has established for new medicines for serious unmet medical needs....The Company's international Phase III trial demonstrated a statistically significant and clinically meaningful extension of median survival in both newly diagnosed and recurrent GBM in patients treated with DCVax-L compared with independently selected, matched, contemporaneous, pre-specified external controls."

European regulatory • P3 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Northwest Biotherapeutics Provides Update On Final Preparations For Marketing Authorization Application (PRNewswire) - "Northwest Biotherapeutics...provided an update today about the final preparations for the Marketing Authorization Application (MAA) that will be submitted to the Medicines and Healthcare Products Regulatory Agency (MHRA) (the equivalent of the U.S. FDA) in the U.K. for commercial approval of the Company's DCVax-L treatment for glioblastoma....The Company provided an update that most of the work has been completed on the key section of the MAA that remained to be done at the time of the prior update, as well as on required supporting documents, the majority of which have been delivered to the publisher/QC team. That team is now under way on this final stage of their work."

European regulatory • Glioblastoma

Multiphase combined treatment, including individualized multimodal immunotherapy for adults with GBM: single institute real world medical data in the light of clinical trial research data (SNO 2023) - "We designed a multiphase combined treatment using subsequentially 1/ modulated electrohyperthermia and Newcastle Disease Virus therapy to induce immunogenic cell death (ICD) during temozolomide maintenance chemotherapy, 2/ two autologous DC vaccinations (IO-Vac®), and 3/ ICD immunotherapy, long-peptide vaccines and one boost IO-Vac® vaccine. TTF improved the OS in both unmeth and meth patients (17m/27% and 32m/59%), while DCvax®-L improved OS only in meth patients (15m/19% and 30m/58%). These real world data support to prospectively explore the addition of individualized multimodal immunotherapy during and after standard of care, and the role of treatment adaptations during treatment."

Clinical • IO biomarker • Real-world • Real-world evidence • Oncology • CTCs • MGMT • PD-L1

Northwest Biotherapeutics Provides Update On Near Term Plans For Submission of Marketing Authorization Application (PRNewswire) - "Northwest Biotherapeutics...provided an update today about its progress toward submission of a Marketing Authorization Application (MAA) to the Medicines and Healthcare Products Regulatory Agency (MHRA)...in the U.K. for commercial approval of the Company's DCVax®-L treatment for glioblastoma...The Company reported that the majority of the MAA has been completed, and all but one of the key sections of the MAA have been delivered to the publisher...An additional factor in the timeline is that certain expert consultants who are key to this remaining section will be temporarily unavailable during the next two-week period, returning the week of October 30....The Company further anticipates that once this last section of the MAA is delivered to the publisher, they will need about two to three weeks to complete their work on both the last portion and the integrated whole. With this timeline, the submission of the MAA to the MHRA would take place between mid and late November."

European regulatory • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Dendritic cell vaccination for glioblastoma multiforme patients: has a new milestone been reached? (PubMed, Transl Cancer Res) - No abstract available

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Northwest Biotherapeutics Announces Completion of Prerequisites, and Plans for Submission of Marketing Authorization Application (PRNewswire) - "Northwest Biotherapeutics...announces that it plans to submit a Marketing Authorization Application (MAA) in the U.K., to the Medicines and Healthcare Products Regulatory Agency (MHRA) (the equivalent of the U.S. FDA), for commercial approval of the Company's DCVax®-L treatment for glioblastoma....The Company anticipates submitting the MAA in approximately the next 30-45 days. The Company plans to request that the MHRA review the MAA under the 150-business day process that the MHRA has established to accelerate the availability of new medicines for patients in the U.K."

European regulatory • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

DCVax-L Vaccination in Patients with Glioblastoma: Real Promise or Negative Trial? The Debate Is Open. (PubMed, Cancers (Basel)) - "The results of the phase III clinical trial of DCVax-L (autologous tumor lysate-loaded dendritic cell vaccination), which has been shown to increase both median survival and long-term survival in newly diagnosed and relapsed glioblastoma, have been enthusiastically received by the scientific community. However, this study deserves some reflections regarding methodological issues related to the primary endpoint change, the long accrual period, and the suboptimal validity of the external control population used as the comparison arm."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

"Dr. Marnix Bosch Speaks in the Industry Expert Theater $NWBO #DCVaxL #ASCO23 Slides: https://t.co/QfjZvwEcRW https://t.co/UlEXA8mw0O" (@eastvillagetwt)

"Gets through the BBB - phase 3 complete significance. Gbm and rGBM killer. Spread the word! $NWBO. DCVAX-L" (@KryptyPop)

P3 data

"$NWBO DCVAX-L gbm killer!" (@KryptyPop)

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial. (PubMed, JAMA Oncol) - P3 | "To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma...The active treatment was DCVax-L plus SOC temozolomide...In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. ClinicalTrials.gov Identifier: NCT00045968."

Clinical • Journal • P3 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. (PubMed, J Transl Med) - P3; "Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002."

Clinical • Journal • P3 data • Brain Cancer • Glioblastoma • Solid Tumor

Assessment of treatment response to dendritic cell vaccine in patients with glioblastoma using a multiparametric MRI-based prediction model. (PubMed, J Neurooncol) - "Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

The Current Status, Challenges, and Future Potential of Therapeutic Vaccination in Glioblastoma. (PubMed, Pharmaceutics) - "However, recent results from the DCVax-L trial provide some promise for vaccine therapy in GBMs...In this review of GBM management, the promise and challenges of immunotherapy with a focus on therapeutic vaccinations are discussed. Additionally, adjuvant therapies, logistical considerations, and future directions are discussed."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Immune Modulation • Oncology • Solid Tumor

Autologous tumor lysate-loaded dendritic cell vaccination in glioblastoma: What happened to the evidence? (PubMed, Rev Neurol (Paris)) - "Dendritic cell vaccination remains a promising approach for GBM. It is therefore disappointing that due to key methodological limitations, the DCVax-L trial ultimately failed to provide sound conclusions about the potential efficacy of such approach for patients with glioblastoma."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

"$NWBO! Get #DcVax-L to the patients!! #GBM Let's GO!! ⏰💥🙌🏻✅🤩" (@DawnAnnManning)

Clinical

[VIRTUAL] Phase III Clinical Trial to Test the Safety and Efficacy of Autologous Tumor Lysate-Loaded Dendritic Cells in Patients with Newly Diagnosed Glioblastoma (SITC 2020) - P3 | "Following surgery and chemoradiation, patients were randomized 2:1 to receive temozolomide plus DCVax-L or temozolomide plus placebo (i.e., autologous PBMC). All subjects were assessed for progression-free survival(PFS) and overall survival (OS). This trial is registered with clinicaltrials.gov, number NCT00045968."

Clinical • Late-breaking abstract • P3 data • Glioblastoma • Oncology • Solid Tumor

[VIRTUAL] Phase III Clinical Trial to Test the Safety and Efficacy of Autologous Tumor Lysate-Loaded Dendritic Cells in Patients with Newly Diagnosed Glioblastoma (SITC 2020) - P3 | "Following surgery and chemoradiation, patients were randomized 2:1 to receive temozolomide plus DCVax-L or temozolomide plus placebo (i.e., autologous PBMC). All subjects were assessed for progression-free survival(PFS) and overall survival (OS). This trial is registered with clinicaltrials.gov, number NCT00045968."

Clinical • Late-breaking abstract • P3 data • Glioblastoma • Oncology • Solid Tumor

"This isn't applicable to NWBO's DCVax-L." (@Hygro10)