Delving into the Latest Updates on Onamelatucel-L with Synapse

Overview

Basic Info

Drug Type

Immune cell therapy

Synonyms

CANVAXIN

Target-

Action-

Mechanism-

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Melanoma

Originator Organization

CancerVax Corp.

Active Organization-

Inactive Organization

CancerVax Corp.

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Author: Dalgleish, Angus ; Mozzillo, Nicola ; Wagner, Jeffrey ; Gammon, Guy ; Huth, James F ; Pertschuk, Daniel ; Thompson, John F ; Kashani-Sabet, Mohammed ; Stern, Stacey ; Faries, Mark B ; Lee, Jeffrey E ; Nardo, Christopher ; Morton, Donald L ; DeConti, Ronald C ; Elashoff, Robert ; Kelley, Mark C

BACKGROUND:

This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma.

METHODS:

After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156).

RESULTS:

Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival.

DISCUSSION:

In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.

01 Mar 2016·Biologicals : journal of the International Association of Biological StandardizationQ4 · BIOLOGY

Analysis of the in vivo proliferative capacity of a whole cell cancer vaccine

Q4 · BIOLOGY

Article

Author: Koren, Eugene ; Morton, Donald ; Petricciani, John

A polyvalent therapeutic cancer cell vaccine containing three viable, irradiated, replication-incompetent melanoma cell lines (Canvaxin) was administered to over 2500 patients in various clinical studies. This study examines the fate of Canvaxin cells in 16 patients with Stage II, III or IV melanoma, with special attention on assessing the capacity of the vaccine cells to replicate. The survival time and the potential proliferative capacity of irradiated Canvaxin cells in humans was studied by histologic examination of biopsies of injection sites over a two-week period. The overall results show that the vaccine cell mitotic index in skin biopsies (0.12%) was approximately 6 times lower than the control value (0.71%). Similarly, there was an overall trend toward a decrease in mitotic figures during the two week observation periods. Also, there was a trend towards a decrease in the number of vaccine cells and mitotic figures with increasing cycles. The data indicate that Canvaxin cells do not proliferate after intra-dermal injection, and that cells typically associated with an immune response are present at the inoculation sites.

01 Feb 2012·Annals of surgeryQ1 · MEDICINE

Assessment of Prognostic Circulating Tumor Cells in a Phase III Trial of Adjuvant Immunotherapy After Complete Resection of Stage IV Melanoma

Q1 · MEDICINE

Article

Author: John F. Thompson ; Christine Kuo ; Sojun Hoshimoto ; Dave S.B. Hoon ; He Jing Wang ; Nicola Mozzillo ; Mark C. Kelley ; Donald L. Morton ; Mark B. Faries ; Jeffrey E. Lee ; Tatsushi Shingai ; Robert Elashoff

OBJECTIVE:

To verify circulating tumor cell (CTC) prognostic utility in stage IV resected melanoma patients in a prospective international phase III clinical trial.

BACKGROUND:

Our studies of melanoma patients in phase II clinical trials demonstrated prognostic significance for CTCs in patients with AJCC stage IV melanoma. CTCs were assessed to determine prognostic utility in follow-up of disease-free stage IV patients pre- and during treatment.

METHODS:

After complete metastasectomy, patients were prospectively enrolled in a randomized trial of adjuvant therapy with a whole-cell melanoma vaccine, Canvaxin, plus Bacille Calmette-Guerin (BCG) versus placebo plus BCG. Blood specimens obtained pretreatment (n = 244) and during treatment (n = 214) were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction (qPCR) for expression of MART-1, MAGE-A3, and PAX3 mRNA biomarkers. Univariate and multivariate Cox analyses examined CTC biomarker expression with respect to clinicopathological variables.

RESULTS:

CTC biomarker(s) (≥ 1) was detected in 54% of patients pretreatment and in 86% of patients over the first 3 months. With a median follow-up of 21.9 months, 71% of patients recurred and 48% expired. CTC levels were not associated with known prognostic factors or treatment arm. In multivariate analysis, pretreatment CTC (> 0 vs. 0 biomarker) status was significantly associated with disease-free survival (DFS; HR 1.64, P = 0.002) and overall survival (OS; HR 1.53, P = 0.028). Serial CTC (>0 vs. 0 biomarker) status was also significantly associated with DFS (HR 1.91, P = 0.02) and OS (HR 2.57, P = 0.012).

CONCLUSION:

CTC assessment can provide prognostic discrimination before and during adjuvant treatment for resected stage IV melanoma patients.

100 Deals associated with Onamelatucel-L

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 3	United States	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Australia	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Brazil	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Canada	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	France	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Germany	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Ireland	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Israel	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Italy	CancerVax Corp.	24 Jan 2003
Melanoma	Phase 3	Netherlands	CancerVax Corp.	24 Jan 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00052156 (Pubmed \| Ann Surg Oncol)	Phase 3	Neoplasm Metastasis Adjuvant	496	BCG+Canvaxin	hggjlxoety(nrebtfpgqm) = rybolweabm kurcdfjfxg (yjijcpvtpk ) View more	-	01 Dec 2017
				BCG+placebo	hggjlxoety(nrebtfpgqm) = nhthtjixlp kurcdfjfxg (yjijcpvtpk ) View more
NCT00052156 (ASCO2012)	Phase 3	Neoplasm Metastasis Adjuvant	496	BCG plus Canvaxin	xlqjjdrysa(hglopufljy) = hlkbgzvzjf kspfemimmz (fbtvmbrgkj ) View more	Positive	20 May 2012
				BCG plus placebo	xlqjjdrysa(hglopufljy) = yckscgqadb kspfemimmz (fbtvmbrgkj ) View more
ASCO2004	Phase 2	Metastatic melanoma	1,856	Polyvalent therapeutic cancer vaccine (Canvaxin)	mkajjjryit(nddaypgsxu) = bfpqsftduu bdbzxgbjqj (emgenmdbbg )	-	15 Jul 2004