Delving into the Latest Updates on GVAX vaccine(The Sidney Kimmel Comprehensive Cancer Center) with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine

Synonyms-

Target-

Action

stimulants

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [4]

Active Indication-

Inactive Indication

Colonic CancerMelanomaMetastatic Colorectal Carcinoma+ [4]

Originator Organization

The Sidney Kimmel Comprehensive Cancer Center

Active Organization-

Inactive Organization

The Sidney Kimmel Comprehensive Cancer Center

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Author: Hacker-Prietz, Amy ; Herman, Joseph M ; Zheng, Lei ; Pawlik, Timothy M ; Cameron, John L ; Narang, Amol K ; Lutz, Eric R ; Parkinson, Rose ; Wolfgang, Christopher L ; Hill, Colin S ; Schulick, Richard ; Onners, Beth ; Laheru, Daniel A ; Sugar, Elizabeth ; Le, Dung T ; Jaffee, Elizabeth M ; Weiss, Matthew J ; Rosati, Lauren

PURPOSELocal and distant progression remains common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase 1 trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy), and stereotactic body radiation therapy (SBRT) followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC.PATIENTS AND METHODSThe study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full-dose FFX. After toxicity review, cohort 2 had SBRT and was switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression.RESULTSNineteen patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after 2 cycles of mFFX. Median overall survival (OS)/disease-free survival (DFS) for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. One- and 2-year OS for cohort 3 was 83%/75%, respectively. At the last follow-up (median = x), 5 patients were alive (42%) in cohort 3.CONCLUSIONSThis is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.

09 Feb 2024·Science Advances

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells

Article

Author: Osipov, Arsen ; Li, Keyu ; Wang, Hao ; Qi, Hanfei ; Lee, Valerie ; He, Jin ; Gai, Jessica ; Thomas, Dwayne L ; Zheng, Lei ; Herman, Joseph M ; Rodriguez, Christina ; Jaffee, Elizabeth M ; Niu, Nan ; Zhang, Tengyi ; McPhaul, Thomas ; Zhu, Qingfeng ; Anders, Robert A ; Wang, Junke ; Parkinson, Rose ; Xia, Tao ; Thompson, Elizabeth D ; Durham, Jennifer ; Laheru, Daniel A ; Narang, Amol K

Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti–PD-1 antibody (a–PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a–PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a–PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB + CD8 + T cells, T H 1, and T H 17, which are associated with longer survival, however increases immunosuppressive M2-like tumor-associated macrophages (TAMs). Adding SBRT to GVAX/a–PD-1 shortens the distances from PD-1 + CD8 + T cells to tumor cells and to PD-L1 + myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.

01 Sep 2021·Molecular Therapy - Nucleic AcidsQ2 · MEDICINE

Aptamer-mediated transcriptional gene silencing of Foxp3 inhibits regulatory T cells and potentiates antitumor response

Q2 · MEDICINE

ArticleOA

Author: Brenneman, Randall J ; Castelucci, Bianca ; Fogagnolo, Carolinne T ; Ruas, Luciana P ; Manrique-Rincón, Andrea J ; Bajgelman, Marcio C ; Berezhnoy, Alexey ; Gilboa, Eli ; Consonni, Sílvio R

The inhibition of immunosuppressive mechanisms may switch the balance between tolerance and surveillance, leading to an increase in antitumor activity. Regulatory T cells play an important role in the control of immunosuppression, exhibiting the unique property of inhibiting T cell proliferation. These cells migrate to tumor sites or may be generated at the tumor site itself from the conversion of lymphocytes exposed to tumor microenvironment signaling. Because of the high similarity between regulatory T cells and other lymphocytes, the available approaches to inhibit this population are nonspecific and may antagonize antitumor response. In this work we explore a new strategy for inhibition of regulatory T cells based on the use of a chimeric aptamer targeting a marker of immune activation harboring a small antisense RNA molecule for transcriptional gene silencing of Fox p 3, which is essential for the control of the immunosuppressive phenotype. The silencing of Fox p 3 inhibits the immunosuppressive phenotype of regulatory T cells and potentiates the effect of the GVAX antitumor vaccine in immunocompetent animals challenged with syngeneic tumors. This novel approach highlights an alternative method to antagonize regulatory T cell function to augment antitumor immune responses.

100 Deals associated with GVAX vaccine(The Sidney Kimmel Comprehensive Cancer Center)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Colorectal Carcinoma	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	26 May 2017
Microsatellite instability-high colorectal cancer	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	26 May 2017
Multiple Myeloma	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	01 Jan 2012
Melanoma	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	01 Sep 2011
Colonic Cancer	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	01 Mar 2008
Neoplasm Metastasis	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	01 Mar 2008
Pancreatic adenocarcinoma	Phase 2	United States	The Sidney Kimmel Comprehensive Cancer Center	01 Jan 2002

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03153410 (CTgov)	Early Phase 1	Pancreatic adenocarcinoma \| Pancreatic Ductal Adenocarcinoma	11	IMC-CS4+cyclophosphamide+GVAX Pancreas Vaccine (GVAX)+pembrolizumab+GVAX	kwqgiytldn(eqpgunqgjt) = gaowjygcqm sspcnuhpsw (zdiwkbvqyz, jhlyxiaxkt - yydinjxohm) View more	-	15 Oct 2024
NCT01595321 (CTgov)	Phase 2	Pancreatic adenocarcinoma	19	Stereotactic Body Radiation+Leucovorin Calcium+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (Cohort 1: SBRT and FOLFIRINOX)	(ntszzcengu) = cqeietigsk mrbqjvbprn (axlrfkdusu, vyixhhtvlk - hxcdrguyly) View more	-	14 Aug 2024
				Stereotactic Body Radiation (Cohort 2: SBRT and Modified FOLFIRINOX)	(ntszzcengu) = evpvbviifs mrbqjvbprn (axlrfkdusu, elymcryykx - gpxbjqyise) View more
NCT00389610 (CTgov)	Phase 2	Pancreatic adenocarcinoma	56	GVAX pancreas vaccine (Previously Vaccinated With GVAX Pancreas Vaccine)	ejktejrmfr(doyhehlogr) = lobhbsuonz rbembjebqc (sopaouygjz, dltryhzfto - ygrneyrsno) View more	-	02 Sep 2022
				GVAX pancreas vaccine (GVAX Pancreas Vaccine Naive)	ejktejrmfr(doyhehlogr) = ryxhdcipub rbembjebqc (sopaouygjz, mmhqukxdzf - szsgtvnomc) View more
NCT02451982 (ASCO_GI2022) Manual	Phase 2	Pancreatic adenocarcinoma Adjuvant \| Neoadjuvant	45	GVAX	(jcsxllkiww) = fsonrcsxae cfifvhugig (nakwjoyryw, 6.0 - NA) View more	Positive	19 Jan 2022
				GVAX+Nivolumab	(jcsxllkiww) = urahayziux cfifvhugig (nakwjoyryw, 7.49 - NA) View more
NCT02981524 (Pubmed \| Cancer Med) Manual	Phase 2	Colorectal Cancer	17	cyclophosphamide+pembrolizumab+GVAX	dvnbxdtrvp(wzgyryqwst) = sepetrhtrf pjwnvwbwbt (cxetfezijw ) View more	-	01 Feb 2020
NCT02981524 (CTgov)	Phase 2	Microsatellite instability-high colorectal cancer \| Metastatic Colorectal Carcinoma	17	CY+GVAX+pembrolizumab	(mhxnlmiacz) = wjxkkaoszq dwomacmwct (kkbuwxwphj, bncvbizolp - tiemfrzqxw) View more	-	08 Oct 2019
NCT02243371 (CTgov)	Phase 2	Pancreatic adenocarcinoma metastatic \| Adenocarcinoma	93	CRS-207+nivolumab+CY+GVAX (Arm A: CY/ GVAX/ CRS-207/ Nivolumab)	(gptzdxokjj) = ygphjcejnq cwngwvachk (yarnttzktw, alzrrugvgl - pmsdbdeulm) View more	-	08 Oct 2019
				CRS-207+CY+GVAX (Arm B: CY/ GVAX/ CRS-207)	(gptzdxokjj) = cdxcesjwii cwngwvachk (yarnttzktw, gktgvnkhzi - idqmvdbdea) View more
NCT00727441 (CTgov)	Phase 2	Pancreatic adenocarcinoma	87	GVAX pancreatic cancer vaccine (Arm A)	(ifdidwiwjw) = mwaifmedee rnfqpwcamk (sltbwueoqy, gmysgsjppf - wafjyjzuqh)	-	05 Jun 2019
				Cyclophosphamide+GVAX pancreatic cancer vaccine (Arm B)	(ifdidwiwjw) = ythixeakvs rnfqpwcamk (sltbwueoqy, xyedohxufp - lgbhcaiwzs)
NCT01349569 (CTgov)	Phase 2	Multiple Myeloma	19	Lenalidomide+Prevnar-13 Vaccine (Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide)	zuoapotcrr(avypdvoghk) = kqjbamisud uvxhjyfucz (vckqplscoe, vyfhseuisn - ohusfdtkfr) View more	-	15 Jan 2019
				lenalidomide (Pre-vaccine (Baseline))	xhxspmpseo(jhrbzofoyi) = rnwfuirocl jvtfwejxoi (immiuglzfo, kmbntyxbqe - vzakibmooh) View more
NCT00084383 (CTgov)	Phase 2	Pancreatic adenocarcinoma	60	GVAX pancreatic cancer vaccine	(qeeakvskxb) = ethgwluefa pddgwraeev (jbvvzcrspo, hbknyimumn - mfjfdvndcm) View more	-	15 Jul 2013