Rintega (rindopepimut) / Celldex - LARVOL DELTA

Comparative efficacy and safety of therapeutic strategies for EGFRvIII positive recurrent glioblastoma. (PubMed, iScience) - "Rindopepimut (Rind) + Bevacizumab (Beva) emerged as the most promising regimen, supported by its OS advantage in randomized trials, consistently favorable OS and PFS trends, top rankings in all three endpoints, and recommendation by clinical guidelines. Safety analysis showed that Rind + Beva had the lowest incidence of all-grade and grade ≥3 AEs. In conclusion, Rind + Beva represent the leading candidate for EGFRvIII-positive rGBM treatment, with the combination of molecular-targeted vaccines and anti-VEGF antibodies offering a promising strategy."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

protein kinase inhibitors as Targeted therapy for glioblastoma: A meta-analysis of randomized controlled clinical trials. (PubMed, Pharmacol Res) - "The standard treatment for newly diagnosed GBM includes surgical resection, when feasible, followed by radiotherapy and temozolomide-based chemotherapy. Upon disease progression, the anti-vascular endothelial growth factor-A (VEGF-A) monoclonal antibody bevacizumab, can be considered...For instance, when comparing PKI treatment with other treatments, median OS and PFS showed no significant difference (-0.78 months, 95% CI, -2.12-0.55, p=0.25; -0.23 months, 95% CI, -0.79-0.34, p=0.43, respectively), and similar non-significant results were observed in the pooled analyses (OS: HR=0.89, 95% CI, 0.59-1.32, p=0.55; PFS: HR=0.83, 95% CI, 0.63-1.11, p=0.21). Despite these overall negative findings, some data indicate improved clinical outcomes in a subset of GBM patients treated with certain PKIs (i.e., regorafenib) and encourage further research to identify PKIs with better blood-brain barrier penetration and lower risk for resistance development."

Clinical • Journal • Retrospective data • Review • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Targeted agents in patients with progressive glioblastoma-A systematic meta-analysis of randomized clinical trials. (PubMed, Cancer Med) - "The aim of this systematic meta-analysis was to establish evidence for the use of targeted therapies in progressive GB. While some studies demonstrated benefits for OS and/or PFS, those results have to be interpreted with caution as most studies had major methodological weaknesses, including potential differences in sample size, trial design, or the initial distribution of prognostic factors."

Clinical • Journal • Retrospective data • Review • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Peptide-Based Vaccines Versus Dendritic Cell-Based Vaccine Therapies for Patients with Glioblastoma: A Network Meta-analysis of Controlled Clinical Trials (SNO 2024) - "PEPvIII-KLH and Rindopepimut were merged into "Peptide-based vaccines" [PEP], and standard of care (SOC) and (Placebo + SOC) were merged...Conclusion Based on current evidence, DCV vaccines perform better than peptide-based vaccines in reducing mortality in GBM patients. Further trials are required to validate their efficacies."

Retrospective data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Targeted agents in patients with recurrent glioblastoma– a systematic meta-analysis of randomized clinical trials (SNO 2023) - "Experimental treatment was either compared to lomustine (CCNU) alone, in combination with CCNU/temozolomide (TMZ) to CCNU alone or to bevacizumab alone. In these three subgroups, targeted agents associated with improved OS compared to the control arm were regorafenib (RR= 0.50; 95% CI 0.33-0.75), Depatux- M+ TMZ (RR= 0.66; 95% CI 0.44-0.93) and rindopepimut + bevacizumab (RR= 0.53; 95% CI 0.32-0.88)... In this systematic meta-analysis, we provide the current highest level of evidence for the role of targeted therapies in recurrent GB. Even though some studies revealed a benefit either for OS and/or PFS, results have to be critically reviewed regarding initial distribution of prognostic factors, underlying molecular mechanisms, sample size and trial design. There is a need for more specific and personalized study designs using newly obtained tumor tissue and close monitoring of treatment responses to allow for potential modification of treatment if needed."

Retrospective data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination for the Treatment of Non-Small Cell Lung Cancer and Glioblastoma. (PubMed, Vaccines (Basel)) - "For example, the CDX-110 (rindopepimut) NeoAg peptide vaccine derived from the EGFRvIII deletion mutant in combination with temozolomide and radiotherapy has shown efficacy in treating EGFRvIII-harboring glioblastoma multiforme (GBM) patients undergone surgery in multiple Phase I and II clinical trials. The efficacy of NeoAg-targeting peptide vaccines may be further improved by combining with other modalities such as tyrosine kinase or immune checkpoint inhibitor (ICI) therapy, which are currently being tested in animal models and clinical trials. Herein, we review the most current basic and clinical research progress on EGFR-targeted peptide vaccination for the treatment of NSCLC and other solid tumor types."

IO biomarker • Journal • Review • Tumor-specific neoantigens • Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Immunotherapy as a New Therapeutic Approach for Brain and Spinal Cord Tumors. (PubMed, Adv Exp Med Biol) - "With respect to cancer vaccines, rindopepimut has been well-studied in glioblastoma (GBM) patients with the EGFRvIII mutation, with early results from phase II trials showing possible efficacy in carefully selected GBM patients...However, it is important to keep in mind that the field is still in its infancy and many clinical trials are still early-phase. Several, clinical trials are currently underway to further explore the role of immunotherapy for CNS malignancies."

IO biomarker • Journal • Brain Cancer • Chordoma • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Herpes Simplex • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • HER-2 • IL2

Efficacy and safety of bevacizumab combined with other therapeutic regimens for treatment of recurrent glioblastoma: A network meta-analysis. (PubMed, World Neurosurg) - "Both Bev + CCNU and Bev + rindopepimut could be considered as effective therapies for treating the recurrent glioblastoma according to the network meta-analysis results. Among them, Bev + rindopepimut therapy seems to be safer and more effective. Moreover, we found that Bev + Iri also appeared to be an effective therapy in a retrospective study."

Journal • Retrospective data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials. (PubMed, Chin J Cancer Res) - "Regorafenib, rindopepimut and neoadjuvant programmed death 1 (PD-1) inhibitors are promising agents for rGBM, while regorafenib is effective in both O-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase (IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec (Toca 511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials."

Clinical • IO biomarker • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

"Remember Rintega? Remember glembatumumab? Now $CLDX reckons it has a future in autoimmune disease. Via @evaluatevantage https://t.co/of6PbZqjTd $MGTA" (@JacobPlieth)

Immunology

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I). (PubMed, Brain Sci) - "Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed."

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

[VIRTUAL] Clinical utility of next generation sequencing in IDH-wildtype glioblastoma: the Dana-Farber Cancer Institute experience. (SNO 2020) - "Four patients received compassionate use therapy targeting EGFRvIII (rindopepimut, n=2), CKD4/6 (abemaciclib, n=1) and BRAFV600E (dabrafenib/trametinib, n=1). While NGS has greatly improved diagnosis and molecular classification, we highlight that NGS remains underutilized in selecting therapy in GBM, even in a setting where clinical trials and off-label therapies are relatively accessible. Continued efforts to develop better targeted therapies and efficient clinical trial design are required to maximize the potential benefits of genomically-stratified data."

Biomarker • Clinical • Next-Generation Sequencing • Glioblastoma • Immune Modulation • Inflammation • Oncology • Solid Tumor • BRAF • CDKN2A • CDKN2B • EGFR • FGFR1 • MLH1 • MSH2 • MSH6 • PDGFRA • PIK3CA • TMB

The evolution of the EGFRvIII (rindopepimut) immunotherapy for glioblastoma multiforme patients. (PubMed) - "EGFRvIII targeting has proven a good way to attack glioblastoma cells by using the immune system. Although in still in development, this approach holds the promise as a great first step toward immune-tailored drugs for the treatment of brain cancers."

Journal • Biosimilar • Immunology • Inflammation • Oncology

Celldex: Risks involved, but set for a transformational year (SeekingAlpha) - CDX 110 to be expanded to other settings, including HNC, lung cancer, a combination trial with Avastin; Final survival data is expected at SNO in 2011

Anticipated data • Anticipated indications expansion • None • Oncology

Celldex: ASCO Investor Event (Celldex) - “Rindopepimut was very well tolerated without additive toxicity to bevacizumab”; “Bevacizumab-naive patients: The randomized Phase 2 study met its primary endpoint of PFS6: 28% vs 16% (p = 0.1163), Overall survival advantage (HR=0.57, p=0.0386) with apparent long-term survival benefit, Advantage to rindopepimut therapy across multiple endpoints including long-term progression-free survival, objective response rate and steroid requirement”; “Bevacizumab-refractory patients: Evidence of rare and prominent tumor regression, Up to 11% objective response rate”; “Activity profile consistent with prior immunotherapy experience”; “Remarkable frequency and level of anti-EGFRvIII immune responses despite prior chemotherapy and growing tumor, Development of anti-EGFRvIII titer may be a biomarker of improved outcome”

P2 data • Oncology

Celldex: SNO 2015 (Celldex) - “Mature randomized survival data continue to show a marked benefit (HR=0.53, p=0.0137) with long-term survival in this small trial; Long term survival not predicted by prognostic patient characteristics, Advantage to rindopepimut therapy across multiple endpoints including long-term progression-free survival, objective response rate and steroid requirement”; “The addition of rindopepimut to bevacizumab did not significantly increase toxicity: Associated with reduction in steroid usage”; “Remarkable frequency and level of anti-EGFRvIII immune responses despite prior chemotherapy and growing tumor: EGFRvIII antibody response correlates with potent effector function and improved clinical outcome”; “Activity profile consistent with prior immunotherapy experience”

P3 data • Biosimilar • Oncology

Celldex: Annual Report 2013 (Celldex) - Anticipated patent protection covering commercial use in major international territories through 2026; Anticipated patent protection relating to methods of manufacture and formulation in the US and major international territories through 2030

Anticipated patent expiry • Oncology

Celldex: Q4 & FY 2013 Results (Celldex) - Anticipated enrollment completion in P3 ACT IV trial for glioblastoma in mid-2014; Anticipated completion of enrollment in P2 ReACT trial for refractory glioblastoma in Q4 2014; Anticipated data from P2 ReACT trial for refractory glioblastoma by YE 2014

Anticipated enrollment status • Anticipated P2 data • Oncology

Rindopepimut: a promising immunotherapeutic for the treatment of glioblastoma multiforme (Immunotherapy) - “This review will outline the development of rindopepimut, as well as the current status of this vaccine.” 

Review • Oncology

Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma (Core Evid) - Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral & cellular immune responses; Phase I & II clinical trials have demonstrated significantly higher PFS & OS times in vaccinated pts with EGFRvIII-expressing GBM tumors; Side effects are minimal & mainly consist of hypersensitivity reactions; Due to the efficacy & safety of rindopepimut, it is a promising therapy for pts with GBM

Review • Oncology

"'ACT IV: Rindopepimut Not Effective for Glioblastoma' via @Medscape https://t.co/p3NrygeeWG #glioblastoma #clinicaltrials" (@fsg_cns)

Biosimilar • Oncology • Solid Tumor

Celldex Therapeutics: Q2 2013 Results (Celldex) - Anticipated data from P2 ReACT (Avastin combo) trial for recurrent glioblastoma at the Society for Neuro-Oncology (SNO) annual meeting (Nov 21-24, 2013)

Anticipated P2 data • Oncology

A study of rindopepimut/GM-CSF in patients with relapsed EGFRvIII-positive glioblastoma (ReACT) (clinicaltrials.gov) - P2, N=168; Sponsor: Celldex; Recruiting; Completion date: Mar 2014 -> Jun 2015.

Trial completion date • Oncology

Celldex: Morgan Stanley Healthcare Conference (Celldex) - Anticipated go/no-go decision for P3 ACT IV trial for glioblastoma in mid-2015; Anticipated enrollment completion in P3 ACT IV trial for glioblastoma in Oct/Nov 2014

Anticipated enrollment status • Trial status • Oncology

Celldex down 9.4% (SeekingAlpha) - “2014 guidance includes completing the accruals of the P3 ACT IV and P2 ReACT clinical trials for rindopepimut…” 

Enrollment change • Oncology