Delving into the Latest Updates on CEA-targeted vaccine(Etubics Corp.) with Synapse

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.

01 Sep 2017·IUBMB LifeQ3 · BIOLOGY

A novel humanized anti‐tumor necrosis factor‐related apoptosis‐inducing ligand‐R2 monoclonal antibody induces apoptotic and autophagic cell death

Q3 · BIOLOGY

Article

Author: Liu, Yanxin ; Chen, Longfei ; Hao, Zhenliang ; Qiu, Yuhe ; Cai, Jiong ; Zheng, Dexian ; Zhang, Shuyong

AbstractIt is well known that the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL/TNFSF10) is specifically expressed in various tumor cells, but less or no expression in most normal tissues and cells. While TRAIL engages with its native death receptors, TRAIL receptor 1 (TRAIL‐R1) or 2 (TRAIL‐R2), usually elicits the tumor cell death by apoptosis. In this study, we report that a novel humanized monoclonal antibody against TRAIL‐R2 (named as zaptuzumab) well remain the biological activity of the parental mouse antibody AD5‐10 inducing cell death in various cancer cells, but little effect on normal cells. Zaptuzumab also markedly inhibited the tumor growth in the mouse xenograft of NCI‐H460 without toxicity to the liver and kidney, and the efficacy of tumor suppression was increased significantly while it combined with cis‐dichlorodiamineplatinum. Especially, 131I‐labeled zaptuzumab injected into mouse tail vein specifically targeted to the xenograft of the lung cancer cells. Confocal analysis showed that zaptuzumab bound with TRAIL‐R2 on cell surface could be quickly internalized and transferred into the lysosome. Furthermore, zaptuzumab possessed a high level of antibody‐dependent cytotoxicity as well as complement‐dependent cytotoxicity. Study on the mechanisms of cell death induced by zaptuzumab showed that it efficiently induced both caspase‐dependent apoptosis and autophagic cell death. These data suggest that the humanized anti‐TRAIL‐R2 monoclonal antibody or the second generation of the antibody may have an important clinical usage for cancer immunotherapy. © 2017 IUBMB Life, 69(9):735–744, 2017

100 Deals associated with CEA-targeted 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
Transitional Cell Carcinoma	Phase 1	-	ImmunityBio, Inc.	01 Dec 2017
Triple Negative Breast Cancer	Phase 1	-	ImmunityBio, Inc.	01 Dec 2017
Breast Cancer	Phase 1	US	ImmunityBio, Inc.	26 Jun 2017
Lung Cancer	Phase 1	US	ImmunityBio, Inc.	26 Jun 2017
Pancreatic Cancer	Phase 1	US	ImmunityBio, Inc.	26 Jun 2017
Triple Negative Breast Cancer	Discovery	-	ImmunityBio, Inc.	01 Dec 2017
Colonic Cancer	Discovery	US	ImmunityBio, Inc.	26 Jun 2017
Ovarian Cancer	Discovery	US	ImmunityBio, Inc.	26 Jun 2017
Thyroid Cancer	Discovery	US	ImmunityBio, Inc.	26 Jun 2017
Liver Cancer	Discovery	US	-	-

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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	uhlsjvoqbj(spalnlzbes) = gxfafqtlqj uipombvjho (diychrxkxn, fcegjyplcc - lgnhgcguvl) 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	mihbthrngq(bakckqaxer) = rtvxptwogf ogrlxrssvr (izscucjfwy, rpnslqlflm - mukxghhloh) View more	-	09 Aug 2024
NCT03127098 (CTgov)	Phase 1/2	Lung Cancer \| Ovarian Cancer \| Colonic Cancer \| Breast Cancer \| Pancreatic Cancer \| Thyroid Cancer	3	ALT-803+ETBX-011	lyffaiowam(ongbrqiadg) = svqixbenam ujapeiycmc (jfwajmykka, dzjuzguhda - tdwnzurxma) View more	-	06 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	rxhyzmuduu(umejvzyuvf) = podhrvnyeg jrcshmkymz (ayqtrpsumz, unkspcjczc - rcakxayolv) View more	-	05 Aug 2024
NCT03136406 (QUILT-3.039, CTgov)	Phase 1/2	Pancreatic Cancer	3	avelumab+ALT-803+GI-4000+Nab-paclitaxel+cyclophosphamide+Leucovorin+Bevacizumab+ETBX-011+Oxaliplatin+5-fluorouracil+Capecitabine	aorjywpxvf(vqgdetkzqn) = grfpjhnyfh aqpxocfzmk (ouxkpphflq, xospgjzdbe - mqojjnzpbn) View more	-	11 Jun 2024
NCT03387098 (P713, CTgov)	Phase 1/2	Pancreatic Cancer	4	SBRT+Aldoxorubicin HCl+GI-4000+lovaza+ETBX-011+fluorouracil+ALT-803+Nab-paclitaxel+Cyclophosphamide+Avelumab+haNK for infusion+Leucovorin+Bevacizumab+Oxaliplatin+Capecitabine	twokfkwkcn(snmqirwqql) = xwljceilui mtnyslwnhq (txeccnkqww, cruesktial - bswloqsqly) View more	-	22 May 2024
NCT01147965 (ASCO2014)	Phase 1/2	Metastatic Colorectal Carcinoma	35	ETBX-011	(xkdgfenymm) = gaotkxjnuf qeludihgly (zfguzdlgsd ) View more	-	20 May 2014
AACR2013	Phase 1/2	Advanced Colorectal Adenocarcinoma	32	ETBX-011	(hhkvnuxyjc) = mtfgbfyuvv uhlouvpvqh (pdscirsrfh )	-	15 Apr 2013
ASCO2012	Phase 1	Pancreatic adenocarcinoma	19	10 μg CEA-vac	sxgfbrxqfz(auqqbyaryv) = lykcxlvufc feecovvfre (emdfseisok )	-	20 May 2012
ASCO2012	Phase 1	Pancreatic adenocarcinoma	19	100 μg CEA-vac	sxgfbrxqfz(auqqbyaryv) = gpicumdlzr feecovvfre (emdfseisok )	-	20 May 2012