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

AbstractBackgroundThis was a single‐arm, phase 2 clinical trial of Bavarian Nordic (BN)‐Brachyury vaccine plus radiotherapy (RT) designed to determine the objective response rate (ORR), progression‐free survival (PFS), and safety of the combination in chordoma.MethodsA total of 29 adult patients with advanced chordoma were treated with two subcutaneous priming vaccine doses of modified vaccinia Ankara‐Bavarian Nordic (MVA‐BN)‐Brachyury and one vaccine dose of fowlpox virus (FPV)‐Brachyury before RT. After RT, booster vaccinations were given with FPV‐Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). A minimum RT dose of >8 Gy in one fraction for each target was required. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients.ResultsTwo of 26 evaluable patients experienced durable partial response (PR) (ORR of 7.7%; 90% confidence interval [CI], 2.6–20.8]) by mRECIST 1.1. A total of 21 patients (80.8%; 90% CI, 65.4–90.3) had stable disease, and three patients (11.5%; 90% CI, 4.7–25.6) had progressive disease as best response per mRECIST 1.1. Median PFS was not reached during the study.ConclusionsThis trial confirms the safety of BN‐Brachyury and RT. Although the study did not meet the predefined study goal of four responses in 29 patients, we did observe two PRs and a PFS of greater than 2 years. For a vaccine‐based study in chordoma, an ultra‐rare disease where response rates are low, a randomized study or novel trial designs may be required to confirm activity.

11 Mar 2022·The OncologistQ2 · MEDICINE

A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer

Q2 · MEDICINE

Article

Author: Tsai, Yo-Ting ; Cordes, Lisa M ; Strauss, Julius ; Schlom, Jeffrey ; McMahon, Sheri ; Abdul Sater, Houssein ; Gatti-Mays, Margaret E ; Jochems, Caroline ; Steinberg, Seth M ; Bilusic, Marijo ; Gulley, James L ; Kim, Sunnie S ; Gandhy, Shruti ; Donahue, Renee N ; Marshall, John L ; Weinberg, Benjamin A ; Marte, Jennifer L ; Redman, Jason M ; Redmond, Erica

AbstractBackgroundFOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine.MethodsPatients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed.ResultsSix patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8.8 months (95% CI: 3.3-17.0 months) versus 10.1 months (95% CI: 3.6-16.1 months), respectively; hazard ratio 1.061 [P = .91; 95% CI: 0.380-2.966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = .020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint.ConclusionsSOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy. Although a tumor-directed immune response is necessary for T-cell–mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit.

01 Jun 2020·The OncologistQ2 · MEDICINE

A Phase I Trial Using a Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury)-Based Immunotherapy Vaccine Regimen in Patients with Advanced Cancer

Q2 · MEDICINE

Article

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.

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
Colorectal Cancer	Preclinical	US	NantKwest, Inc.	25 May 2018
Hepatocellular Carcinoma	Preclinical	US	ImmunityBio, Inc.	25 May 2018
Non-Small Cell Lung Cancer	Preclinical	-	ImmunityBio, Inc.	01 Feb 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
Squamous Cell Carcinoma of Head and Neck	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Transitional Cell Carcinoma	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Triple Negative Breast Cancer	Preclinical	-	ImmunityBio, Inc.	01 Dec 2017
Squamous Cell Carcinoma	Discovery	US	NantKwest, Inc.	13 Jan 2018

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03586869 (QUILT-3.080, CTgov)	Phase 1/2	Pancreatic Cancer	3	Avelumab+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+fluorouracil+ALT-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+haNK for infusion+Leucovorin+GI-6207+bevacizumab+Oxaliplatin+Capecitabine	nzieopsnxx(bshhrgnzmf) = jouvmwhzvo ndmjgspkmx (zbmkfgumbx, nvidznrbvi - ynrpztoogi) 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+ETBX-011+5-fluorouracil+N-803+nab-paclitaxel+CYCLOPHOSPHAMIDE+Avelumab+haNK for Infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	dlalmyhinr(xwnxqjmcku) = jocbfjbeht vxrkpbmzrq (etmihjujor, exbjvbpabb - kcsijvlixt) 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+ETBX-011+Necitumumab+fluorouracil+N-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+Avelumab+haNK for infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	wodkvzsjhs(fmudowunwu) = ubnkurenxv litdfnspku (mbqhqmrfxj, houojeuafy - howaosehsj) View more	-	05 Aug 2024
NCT03481816 (CTgov)	Phase 1	Castration-Resistant Prostatic Cancer	18	ETBX-061; adenoviral MUC1 vaccine+ETBX-071; adenoviral PSA vaccine+ETBX-051; adenoviral brachyury vaccine (Arm 1/Dose De-Escalation)	xcrctampbc(sxodwmjtei) = xvfugkdavv qkaeipnapm (wbgsqaxlhz, zewjfepljz - ipmvapafaj) View more	-	22 Dec 2020
NCT03481816 (CTgov)	Phase 1	Castration-Resistant Prostatic Cancer	18	ETBX-061; adenoviral MUC1 vaccine+ETBX-071; adenoviral PSA vaccine+ETBX-051; adenoviral brachyury vaccine (Arm 2/Dose Expansion)	xcrctampbc(sxodwmjtei) = fqcooczgfu qkaeipnapm (wbgsqaxlhz, ddqebesbfw - tmphytaizx) 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))	shzgxgmfyl(xooypfzkmb) = ejzywrxpio mikyhqclzo (czuoiwsqkn, qbgiktotke - uqhjkjbhdf) 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))	shzgxgmfyl(xooypfzkmb) = apbvcdpnrp mikyhqclzo (czuoiwsqkn, xmfxzawrpd - ssezydzzxf) View more	-	23 Dec 2019
NCT03481816 (ESMO2019)	Phase 1	Metastatic castration-resistant prostate cancer	12	Ad5 PSA/MUC-1/Brachyury Vaccine	(fttcsqsxha) = wfhhqorwjn oljhyelbpn (ldktvgigeu )	-	30 Sep 2019