Delving into the Latest Updates on CMB-305 with Synapse

Overview

Basic Info

Drug Type

Shared antigen vaccine, Therapeutic vaccine

Synonyms

+ [4]

Target

NY-ESO-1

Mechanism

NY-ESO-1 inhibitors(Cancer/testis antigen 1 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesOther Diseases+ [3]

Active Indication-

Inactive Indication

Locally Advanced Soft Tissue SarcomaMelanomaMyxoid Liposarcoma+ [3]

Originator Organization

Immune Design Corp.

Active Organization-

Inactive Organization

Immune Design Corp.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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This is an open-label Phase 2 randomized study that will examine the use of the study agents, CMB305 (sequentially administered LV305 which is a dendritic cell-targeting viral vector expressing the New York Esophageal Squamous Cell Carcinoma 1 gene [NY-ESO-1] and G305 which is a NY-ESO-1 recombinant protein plus glucopyranosyl lipid adjuvant-stable emulsion [GLA-SE]) in combination with atezolizumab or atezolizumab alone, in participants with locally advanced, relapsed or metastatic sarcoma (synovial or myxoid/round cell liposarcoma) expressing the NY-ESO-1 protein.
There is no formal primary hypothesis for this study.

Start Date29 Apr 2015

Sponsor / Collaborator

Genentech, Inc.

NCT02387125 / TerminatedPhase 1

A Phase 1b Study Evaluating the Safety, Tolerability and Immunogenicity of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

This is a Phase 1b, open label, multi-center study of CMB305 (sequentially administered LV305 [a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene] and G305 [NY-ESO-1 recombinant protein plus GLA-SE]) in patients with melanoma, sarcoma, ovarian cancer, or non-small cell lung cancer that express NY-ESO-1.

Start Date28 Feb 2015

Sponsor / Collaborator-

100 Clinical Results associated with CMB-305

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100 Translational Medicine associated with CMB-305

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100 Patents (Medical) associated with CMB-305

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3

Literatures (Medical) associated with CMB-305

20 Apr 2022·Journal of Clinical OncologyQ1 · MEDICINE

Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1

Q1 · MEDICINE

Article

Author: Pollack, Seth M. ; Yakovich, Adam ; Keedy, Vicki L. ; Chen, Michael ; Attia, Steven ; Choy, Edwin ; Agulnik, Mark ; Van Tine, Brian A. ; Yurasov, Sergey ; von Mehren, Margaret ; Chawla, Sant P. ; Verschraegen, Claire F. ; Okuno, Scott H. ; Bohac, G. Chet ; Elias, Anthony D. ; Riedel, Richard F. ; Lu, Hailing ; Livingston, Michael B. ; Maki, Robert G. ; Ganjoo, Kristen N. ; Philip, Tony

PURPOSE CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1–specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti–programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma. PATIENTS AND METHODS Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed. RESULTS A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1–specific T cells ( P = .01) and NY-ESO-1–specific antibody responses ( P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02). CONCLUSION Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti–programmed death ligand-1 therapies merits further evaluation in other clinical contexts.

01 Jan 2020·OncoImmunologyQ2 · MEDICINE

A Phase 1b Study Evaluating the Safety, Tolerability, and Immunogenicity of CMB305, a Lentiviral-Based Prime-Boost Vaccine Regimen, in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

Q2 · MEDICINE

ArticleOA

Author: Chen, Michael ; Sankhala, Kamalesh K. ; Kenney, Richard T. ; Kim, Joseph W. ; Chawla, Sant P. ; Morris, John C. ; Kim-Schulze, Seunghee ; Lu, Hailing ; Yishak, Mahlet ; Block, Matthew S. ; Jones, Robin L. ; Do, Khanh ; Gnjatic, Sacha ; Yakovich, Adam ; Druta, Mihaela ; Ter Meulen, Jan ; Hwu, Patrick ; Bohac, Chet ; Tuballes, Kevin ; Somaiah, Neeta ; Pollack, Seth M.

Preclinical data suggest that a "prime-boost" vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broad anti-NY-ESO-1 immune response. It is composed of LV305, which is an NY-ESO-1 expressing lentiviral vector, and G305, a recombinant adjuvanted NY-ESO-1 protein. This multicenter phase 1b, first-in-human trial evaluated CMB305 in patients with NY-ESO-1 expressing solid tumors. Safety was examined in a 3 + 3 dose-escalation design, followed by an expansion with CMB305 alone or in a combination with either oral metronomic cyclophosphamide or intratumoral injections of a toll-like receptor agonist (glucopyranosyl lipid A). Of the 79 patients who enrolled, 81.0% had sarcomas, 86.1% had metastatic disease, and 57.0% had progressive disease at study entry. The most common adverse events were fatigue (34.2%), nausea (26.6%), and injection-site pain (24.1%). In patients with soft tissue sarcomas, a disease control rate of 61.9% and an overall survival of 26.2 months (95% CI, 22.1-NA) were observed. CMB305 induced anti-NY-ESO-1 antibody and T-cell responses in 62.9% and 47.4% of patients, respectively. This is the first trial to test a prime-boost vaccine regimen in patients with advanced cancer. This approach is feasible, can be delivered safely, and with evidence of immune response as well as suggestion of clinical benefit.

Expert Review of VaccinesQ2 · MEDICINE

The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients

Q2 · MEDICINE

Review

Author: Pollack, Seth M.

INTRODUCTIONSynovial Sarcoma (SS) and Myxoid Round Cell Liposarcoma (MRCL) are devastating sarcoma subtypes with few treatment options and poor outcomes in the advanced setting. However, both these diseases may be ideal for novel immunotherapies targeting the cancer-testis antigen, NY-ESO-1.AREAS COVEREDIn this review, we discuss the novel NY-ESO-1 targeted vaccine regimen, CMB305. This regimen uses a unique integration-deficient, dendritic-cell targeting lentiviral vector from the ZVex® platform, LV305, in order to prime NY-ESO-1 specific T cells. LV305 has single agent activity, and, in one case, caused a durable partial response in a refractory SS patient. CMB305 also includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A. CMB305 induces NY-ESO-1 specific T cell responses in both SS and MRC patients and these patients had excellent overall survival (OS) outcomes in the initial phase I study.EXPERT COMMENTARYCMB305 is a therapeutic vaccine regimen targeting NY-ESO-1 based on the lentiviral vaccine vector, LV305. Phase I studies have proven this vaccine is active immunologically. Data suggesting this vaccine may improve OS for SS and MRCL patients is exciting but early, and on-going work is testing the impact of CMB305 on patient outcomes.

100 Deals associated with CMB-305

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Synovial Sarcoma	Phase 3	US	Immune Design Corp.	21 Jun 2018
Synovial Sarcoma	Phase 3	US	Immune Design Corp.	21 Jun 2018
Locally Advanced Soft Tissue Sarcoma	Phase 3	US	-	29 Apr 2015
Myxoid Liposarcoma	Phase 3	US	-	29 Apr 2015
Melanoma	Phase 3	US	-	28 Feb 2015
Non-Small Cell Lung Cancer	Phase 3	US	-	28 Feb 2015
Ovarian Cancer	Phase 3	US	-	28 Feb 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02387125 (Pubmed \| Oncoimmunology) Manual	Phase 1	Locally Advanced Malignant Neoplasm	79	cyclophosphamide+glucopyranosyl lipid A+CMB305	(slxupxpytr) = fatigue (34.2%), nausea (26.6%), and injection-site pain (24.1%) qitjudnnkv (pdwgihcfdx )	Positive	19 Nov 2020
NCT02609984 (V943A-002 \| IMDZ-C232, CTgov)	Phase 2	Locally Advanced Soft Tissue Sarcoma \| Synovial Sarcoma \| Myxoid Liposarcoma	89	Atezolizumab+CMB305 (CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab)	cttauwpyun(lgoozyudqu) = effgpdbhiw mogmoxqdjb (gpbuvzytta, xocyxbgood - krzvpeymfm) View more	-	14 May 2020
NCT02609984 (V943A-002 \| IMDZ-C232, CTgov)	Phase 2		89	Atezolizumab (Atezolizumab)	cttauwpyun(lgoozyudqu) = narcytofaq mogmoxqdjb (gpbuvzytta, spvprjlibd - eezltwbutt) View more	-	14 May 2020
NCT02609984 (V943A-002 \| IMDZ-C232, ASCO2019) Manual	Phase 2	Sarcoma \| Myxoid Liposarcoma CTAG1B Positive	88	atezolizumab+CMB305	(jypforhdam) = mluokkxyvx ffeewnsvhb (gwntnkdpak, 11.0 - NR) View more	Positive	26 May 2019
NCT02609984 (V943A-002 \| IMDZ-C232, ASCO2019) Manual	Phase 2	Sarcoma \| Myxoid Liposarcoma CTAG1B Positive	88	atezolizumab	(jypforhdam) = ucuznqddcd ffeewnsvhb (gwntnkdpak, 4.6 - 26.1) View more	Positive	26 May 2019
NCT02387125 (ESMO2018)	Phase 1	Soft Tissue Sarcoma Maintenance	25	CMB305 regimen	lrgitkchri(nolcsztkpb) = Most treatment related adverse events were Grade 1 or 2; one Grade 3 (prostatic pain); no grade 4 or 5 events. owpccwuizh (ajpeqimvhr ) View more	Positive	22 Oct 2018
Phase 1 trials of LV305 and CMB305 (ASCO2017)	Phase 1	Neoplasms	62	CMB305	bkdeaebvfn(pghqdbmoqq) = ufuolohzsq eblzbtkces (avxiejbhzo ) View more	-	30 May 2017
Phase 1 trials of LV305 and CMB305 (ASCO2017)	Phase 1	Neoplasms	62	LV305	bkdeaebvfn(pghqdbmoqq) = qzlbtqcgib eblzbtkces (avxiejbhzo ) View more	-	30 May 2017
NCT02387125 (CMB305, ASCO2017)	Phase 1	Soft Tissue Sarcoma	25	CMB305	kxqsrbjbuo(jcumbzbugi) = uvsjgclegm cxddmnqdgc (droapraevh ) View more	-	30 May 2017