Delving into the Latest Updates on Adenoviral brachyury vaccine(Etubics Corp.) with Synapse

Author: Bilusic, Marijo ; Madan, Ravi A. ; Marté, Jennifer L. ; Gulley, James L. ; Schlom, Jeffrey ; Cordes, Lisa M. ; Strauss, Julius ; Karzai, Fatima ; Redman, Jason M. ; Sater, Houssein Abdul ; Gatti-Mays, Margaret E. ; Palena, Claudia ; Steinberg, Seth M. ; McMahon, Sheri ; Donahue, Renee N. ; Orpia, Alanvin ; Burmeister, Andrea

AbstractLessons LearnedConcurrent ETBX-011, ETBX-051, and ETBX-061 can be safely administered to patients with advanced cancer. All patients developed CD4+ and/or CD8+ T-cell responses after vaccination to at least one tumor-associated antigen (TAA) encoded by the vaccine; 5/6 patients (83%) developed MUC1-specific T cells, 4/6 (67%) developed CEA-specific T cells, and 3/6 (50%) developed brachyury-specific T cells. The presence of adenovirus 5-neutralizing antibodies did not prevent the generation of TAA-specific T cells.BackgroundA novel adenovirus-based vaccine targeting three human tumor-associated antigens—CEA, MUC1, and brachyury—has demonstrated antitumor cytolytic T-cell responses in preclinical animal models of cancer.MethodsThis open-label, phase I trial evaluated concurrent administration of three therapeutic vaccines (ETBX-011 = CEA, ETBX-061 = MUC1 and ETBX-051 = brachyury). All three vaccines used the same modified adenovirus 5 (Ad5) vector backbone and were administered at a single dose level (DL) of 5 × 1011 viral particles (VP) per vector. The vaccine regimen consisting of all three vaccines was given every 3 weeks for three doses then every 8 weeks for up to 1 year. Clinical and immune responses were evaluated.ResultsTen patients enrolled on trial (DL1 = 6 with 4 in the DL1 expansion cohort). All treatment-related adverse events were temporary, self-limiting, grade 1/2 and included injection site reactions and flu-like symptoms. Antigen-specific T cells to MUC1, CEA, and/or brachyury were generated in all patients. There was no evidence of antigenic competition. The administration of the vaccine regimen produced stable disease as the best clinical response.ConclusionConcurrent ETBX-011, ETBX-051, and ETBX-061 can be safely administered to patients with advanced cancer. Further studies of the vaccine regimen in combination with other agents, including immune checkpoint blockade, are planned.

Frontiers in Oncology

Fast Clearance of the SARS-CoV-2 Virus in a Patient Undergoing Vaccine Immunotherapy for Metastatic Chordoma: A Case Report

Author: Sirajuddin, Arlene ; Pastor, Danielle M ; Lee-Wisdom, Katherine ; Arai, Andrew E ; Gulley, James L ; Korchin, Borys ; Rosing, Douglas R ; Bilusic, Marijo

The emergence of the SARS-CoV-2 virus has been associated with perplexing clinical sequelae and phenomena that often have no clear link to the underlying infection. There is a wide spectrum of symptoms associated with infection, from minimal respiratory complaints to severe multi-organ failure, often resulting in death. Individuals with malignancies, particularly those whose treatments have left them immunocompromised or immunosuppressed, are among the patient populations thought to be at greater risk for more severe illness. A man with aggressive metastatic chordoma contracted the SARS-CoV-2 virus and was diagnosed with COVID-19 while undergoing intravenous brachyury vaccine immunotherapy. His disease course was remarkably mild, and the virus cleared rapidly. Despite a treatment delay of 3 months due to the COVID-19 pandemic, the patient's disease has been stable and tumor-related pain has significantly improved. This suggests not only an intact, functional immune system, but also one that appears to have been responsive to cancer treatment. It has been suggested that individuals undergoing treatment for metastatic cancer are at greater risk of severe SARS-CoV-2-related illnesses and complications. While immunosuppression may be a problem, particularly in those receiving conventional chemotherapeutic agents, it is possible that the non-specific effects of immune-enhancing therapies may confer some protection against SARS-CoV-2.

Cancers

Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review

Review

Author: Xiao, Jianru ; Chen, Zhaoyu ; Fan, Jiefu ; Xu, Wei ; Wang, Xiang ; Li, Bo

Objective: To summarize the function and efficacy of immunotherapy as an adjunctive therapy in the treatment of advanced chordoma. Methods: Literature search was conducted by two reviewers independently. Case reports, case series and clinical trials of immunotherapy for chordoma were retrieved systematically from Pubmed, Web of Science, Scoupus and Cochrane Library. Clinical outcome data extracted from the literature included median progression-free survival (PFS), median overall survival (OS), clinical responses and adverse events (AEs). Results: All studies were published between 2015 and 2022. Twenty-two eligible studies were selected for systemic review. PD-1/PD-L1 immune checkpoint inhibitors (ICIs) were the most common used immunotherapy agents in chordoma, among which Pembrolizumab was the most frequently prescribed. CTLA-4 antibody was only used as combination therapy in chordoma. Dose Limiting Toxicity (DLT) was not observed in any vaccine targeting brachyury, and injection site response was the most frequent AV. The response evaluation criteria in solid tumors (RECIST) were the most generally used evaluation standard in chordoma immunotherapy, and none of the included studies employed the Choi criteria. Conclusions: No clinical data have demonstrated that CTLA-4 ICIs combined with PD-1/PD-L1 ICIs is more effective than ICIs monotherapy in treating chordoma, and ICIs in combination with other therapies exhibit more toxicity than monotherapy. PD-1/PD-L1 ICIs monotherapy is recommended as an immunotherapy in patients with advanced chordoma, which may even benefit PD-L1-negative patients. The brachyury vaccine has shown good safety in chordoma patients, and future clinical trials should focus on how to improve its therapeutic efficacy. The use of immunomodulatory agents is a promising therapeutic option, though additional clinical trials are required to evaluate their safety and effectiveness. RECIST does not seem to be an appropriate standard for assessing medications of intratumoral immunotherapy.

100 Deals associated with Adenoviral brachyury vaccine(Etubics Corp.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Preclinical	United States	ImmunityBio, Inc.	25 May 2018
Unresectable Hepatocellular Carcinoma	Preclinical	United States	ImmunityBio, Inc.	25 May 2018
Melanoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Merkel Cell Carcinoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Ovarian Cancer	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Ovarian Epithelial Carcinoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Squamous Cell Carcinoma of Head and Neck	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Transitional Cell Carcinoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Unresectable Melanoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Squamous Cell Carcinoma	Discovery	United States	NantKwest, Inc.	13 Jan 2018

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Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03563157 (CTgov)	Phase 1/2	Metastatic Colorectal Carcinoma	2	SBRT+Aldoxorubicin Hydrochloride+GI-6301+GI-4000+ETBX-061+Cetuximab+ETBX-051+Leucovorin+ETBX-011+5-Fluorouracil+ALT-803+ETBX-021+nab-paclitaxel+CYCLOPHOSPHAMIDE+Avelumab+haNK+GI-6207+Regorafenib+Oxaliplatin+Capecitabine (NANT Colorectal Cancer (CRC) Vaccine)	(fgdiswxkmt) = zodbnxwtpi xzphplehxz (etqyemsssc, rhrjkccrri - rktejitjge) View more	-	11 Dec 2024
NCT03563157 (CTgov)	Phase 1/2	Metastatic Colorectal Carcinoma	2	Regorafenib (Regorafenib)	uzhwzbsaol(wwohuwkggo) = ucrsvwwiev wznpmhdyrg (jifrpeqlzn, brajprtlnb - awxuqwhrua) View more	-	11 Dec 2024
NCT03586869 (QUILT-3.080, CTgov)	Phase 1/2	Pancreatic Cancer	3	Avelumab+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+Leucovorin+ETBX-011+fluorouracil+ALT-803+ETBX-021+nab-paclitaxel+cyclophosphamide+haNK for infusion+GI-6207+bevacizumab+Oxaliplatin+Capecitabine	(ekhdqiixpo) = zyuqddmdgx gmmuvjentb (gcipvygqly, qyfwjkedmx - mzkyxvmdsg) View more	-	27 Aug 2024
NCT03387085 (QUILT-3.067, CTgov)	Phase 1/2	Triple Negative Breast Cancer	9	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+Leucovorin+ETBX-011+5-Fluorouracil+N-803+nab-paclitaxel+CYCLOPHOSPHAMIDE+Avelumab+haNK for Infusion+GI-6207+cisplatin+Bevacizumab+Capecitabine	(nvgsxoceqe) = vbvugogacp regsipehnv (tzspffzwfr, fkytdbyrfi - uyawpfhcit) View more	-	09 Aug 2024
NCT03387111 (CTgov)	Phase 1/2	Squamous Cell Carcinoma	4	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+cetuximab+ETBX-061+ETBX-051+Leucovorin+ETBX-011+Necitumumab+fluorouracil+N-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+Avelumab+haNK for infusion+GI-6207+cisplatin+Bevacizumab+Capecitabine	gkmumqepkk(pjljrezuxy) = enlyesekgn eozinqkrvh (bkfqipwfyf, fhsgeeqzex - rzoprgafzv) View more	-	05 Aug 2024
NCT03481816 (CTgov)	Phase 1	Castration-Resistant Prostatic Cancer \| Metastatic castration-resistant prostate cancer	18	ETBX-061; adenoviral MUC1 vaccine+ETBX-071; adenoviral PSA vaccine+ETBX-051; adenoviral brachyury vaccine (Arm 1/Dose De-Escalation)	kviiazzcaz(dvmbjmepzg) = qyekqxhidc fbjrehemxy (nfdmlvzimi, czoshbebtx - hcbwmrmehz) View more	-	22 Dec 2020
NCT03481816 (CTgov)	Phase 1		18	ETBX-061; adenoviral MUC1 vaccine+ETBX-071; adenoviral PSA vaccine+ETBX-051; adenoviral brachyury vaccine (Arm 2/Dose Expansion)	kviiazzcaz(dvmbjmepzg) = pictfatdui fbjrehemxy (nfdmlvzimi, eqsgrxmwgc - fodccmfhum) View more	-	22 Dec 2020
NCT03384316 (CTgov)	Phase 1	Lung Cancer \| Colonic Cancer \| Breast Cancer \| Prostatic Cancer \| Advanced cancer	11	adenoviral Carcinoembryonic antigen (CEA) vaccine+ETBX-061+ETBX-051+ETBX-011 (Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP))	gzzrsxqfbd(tkuxzogjpx) = yycuqeorai uyfyjakghf (xdwtgnmtbx, ybyrejkclm - rwrbnpqotb) View more	-	23 Dec 2019
NCT03384316 (CTgov)	Phase 1		11	adenoviral Carcinoembryonic antigen (CEA) vaccine+ETBX-061+ETBX-051+ETBX-011 (Expansion Cohort - 5 x 10^11 Viral Particles (VP))	gzzrsxqfbd(tkuxzogjpx) = nchruzobzh uyfyjakghf (xdwtgnmtbx, aqrtxamcyo - yuhuqcftoc) View more	-	23 Dec 2019
NCT03481816 (ESMO2019)	Phase 1	Metastatic castration-resistant prostate cancer	12	Ad5 PSA/MUC-1/Brachyury Vaccine	(tnjschdpzf) = itgdczqdac aentnbwxry (zrbvnofjxv )	-	30 Sep 2019