A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings.
MUC1 over-expression in renal clear-cell carcinoma (RCC) is associated with poor prognosis. This phase II study determined the efficacy and tolerability of TG4010, a cancer vaccine based on a modified vaccinia virus expressing MUC1 and interleukin-2, in combination with cytokines, as first-line therapy in metastatic RCC. Thirty-seven patients with progressive, MUC1-positive RCC received TG4010 10(8) pfu/inj weekly for 6 weeks, then every 3 weeks until progression, when TG4010 was continued in combination with interferon-α2a and interleukin-2. Assessments included clinical response (primary endpoint), safety, time to treatment failure (TTF), overall survival (OS), and immune response. No objective clinical responses occurred. Five of the 27 evaluable patients (18%) had stable disease for >6 months with TG4010 alone and six of 20 patients (30%) had stable disease for >6 months with TG4010 plus cytokines. Median TTF was 4.1, 3.6, and 9.3 months for monotherapy, combination therapy, and overall, respectively. Median OS was 19.3 months for all patients and 22.4 months combination therapy recipients. The most frequent TG4010-related adverse events were minor-to-moderate injection-site reactions, fatigue, and flu-like symptoms. Six of 28 patients showed a MUC1 CD4+ T cell proliferative response during therapy. Anti-MUC1 CD8+ T cells were detected before and after therapy in 3 and 4 patients, respectively. MUC1-specific CD8+ T cell responses were associated with longer survival. Therapy with TG4010 plus cytokines appears to be feasible and well tolerated in patients with metastatic RCC. However, these data should be interpreted with caution, as additional prospective studies are necessary to clarify the clinical efficacy of this therapy.
Medical Oncology Department, Georges Pompidou European Hospital, 20 rue Leblanc, Paris Cedex 15, France. stephane.oudard@egp.aphp.fr
Stéphane
S
Oudard
Olivier
O
Rixe
Benoit
B
Beuselinck
Claude
C
Linassier
Eugeniu
E
Banu
Jean-Pascal
JP
Machiels
Marion
M
Baudard
François
F
Ringeisen
Thierry
T
Velu
Marie-Aude
MA
Lefrere-Belda
Jean-Marc
JM
Limacher
W H
WH
Fridman
Michel
M
Azizi
Bruce
B
Acres
Eric
E
Tartour
D000293:Adolescent; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D049109:Cell Proliferation; D016207:Cytokines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D018450:Disease Progression; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis / Q000276:immunology; D009362:Neoplasm Metastasis / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
D019496:Cancer Vaccines; D016207:Cytokines; C060192:MUC1 protein, human; D008562:Membrane Glycoproteins; D018396:Mucin-1; C518275:TG4010