Delving into the Latest Updates on PVX-410 with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine

Synonyms

Target

Mechanism

CD138 inhibitors(Syndecan-1 inhibitors), SLAMF7 inhibitors(SLAM family member 7 inhibitors), XBP1 inhibitors(X-box binding protein 1 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [2]

Active Indication

Metastatic Triple-Negative Breast CarcinomaPD-L1 negative Triple Negative Breast CancerMultiple Myeloma+ [2]

Inactive Indication-

Originator Organization

Dana-Farber Cancer Institute, Inc.

Active Organization

OncoPep, Inc.

Emory University

Dana-Farber Cancer Institute, Inc.

+ [4]

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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ImportanceIncreasing evidence suggests the significance of the role of the immune system in the progression of smoldering multiple myeloma (SMM) to symptomatic multiple myeloma (MM). Boosting the immune system via vaccination in the earlier, asymptomatic SMM stage may provide a novel strategy to prevent or slow progression to active MM.ObjectiveTo determine the safety, tolerability, immunogenicity, and anti-MM activity of the PVX-410 multipeptide vaccine with or without lenalidomide.Design, Setting, and ParticipantsThis 3-cohort phase 1/2a multicenter dose-escalation study accrued 22 adults (≥18 years) with SMM with normal organ/marrow function who were human leukocyte antigen A2-positive and at moderate or high risk of progression to MM.InterventionsPatients received 6 doses of PVX-410 emulsified in Montanide ISA 720 VG, 0.4 mg total (0.1 mg/peptide) (n = 3) or 0.8 mg total (0.2 mg/peptide) (n = 9), biweekly via subcutaneous injection. In the combination cohort (n = 10), patients also received three 21-day cycles of lenalidomide, 25 mg, orally daily every 28 days. All patients received 0.5 mL (1 mg) poly-ICLC (2 mg/mL) via intramuscular injection with each PVX-410 dose.Main Outcomes and MeasuresAdverse events (AEs) were evaluated using the Common Terminology Criteria for Adverse Events, version 4.03. PVX-410-specific T lymphocytes by flow cytometry to assess tetramer and interferon (IFN)-γ response. Disease response was assessed by investigators using the International Myeloma Working Group (IMWG) and modified European Group for Bone Marrow Transplantation (EBMT) criteria.ResultsOverall, 14 (64%) patients were men and the median age at enrollment was 56 years in the monotherapy and 57 years in the combination cohorts (overall range, 39-82 years). Six of 12 patients in the monotherapy and 9 of 10 in the combination cohorts were at moderate risk. The PVX-410 vaccine was well tolerated. The most common AEs were mild-to-moderate injection site reactions and constitutional symptoms. Of note, PVX-410 was immunogenic as monotherapy (10 of 11 patients) and in combination with lenalidomide (9 of 9 patients), as demonstrated by an increase in percentage of tetramer-positive cells and IFN-γ cells in the CD3+CD8+ cell population. The combination resulted in greater mean fold increases in proportions of CD3+CD8+ T cells that were tetramer-positive and IFN-γ-positive, statistically significant for IFN-γ-positive cells after 2 and 4 vaccinations. An increase and persistence of vaccine-specific effector memory cells was noted. In total, 7 of 12 patients in the PVX-410-alone cohort had stable disease with 2 of 3 (low-dose cohort) and 1 of 9 of the target-dose cohort progressing (median TTP, 36 weeks), whereas 5 of 12 patients in the combination cohort showed, clinical response, with 1 patient progressing (median TTP not reached).Conclusions and RelevanceOverall, these results suggest that the vaccine is safe and immunogenic in this patient population and support continued study of PVX-410 in SMM.Trial RegistrationClinicalTrials.gov identifier: NCT01718899.

100 Deals associated with PVX-410

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Triple-Negative Breast Carcinoma	Phase 2	-	OncoPep, Inc.	30 Apr 2022
PD-L1 negative Triple Negative Breast Cancer	Phase 2	-	OncoPep, Inc.	30 Apr 2022
Multiple Myeloma	Phase 2	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Multiple Myeloma	Phase 2	-	OncoPep, Inc.	-
Multiple Myeloma	Phase 2	-	Mass General Brigham, Inc.	-
Multiple Myeloma	Phase 2	-	Dana-Farber Cancer Institute, Inc.	-
Multiple Myeloma	Phase 2	-	Emory University	-
Triple Negative Breast Cancer	Phase 1	US	AstraZeneca PLC	01 Aug 2016
Smoldering Multiple Myeloma	Phase 1	US	OncoPep, Inc.	01 Nov 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01718899 (Pubmed \| JAMA Oncol) Manual	Phase 1/2	Smoldering Multiple Myeloma	22	PVX-410 Vaccine	(erpebuccai) = hxbmzdedfo rywwnokfxp (yoewngoecs ) View more	Positive	01 Dec 2018
				Lenalidomide+PVX-410 Vaccine	(zbqnzfqtnl) = qpebjbjenc eikwdkdxex (ldoxyoonrr ) View more
NCT02886065 (BusinessWire) Manual	Phase 1/2	Multiple Myeloma	26	Durvalumab+PVX 410	(fynlyziyqr) = vuwaearttf pgscdomphd (ghrnliqzqz ) View more	Positive	28 Nov 2016
				Durvalumab+Lenalidomide+PVX 410	(fynlyziyqr) = zitnlrzgyy pgscdomphd (ghrnliqzqz ) View more