Lucanix Anti-TGF-β2 Vaccine May Prolong NSCLC Survival

ATLANTA—A vaccine that blocks production of transforming growth factor-beta 2 (TGF-β2) extended 1-year survival in patients with advanced non-small-cell lung cancer (NSCLC) in a phase II study and should be moved forward into phase III clinical trials, lead investigator John J. Nemunaitis, MD, reported at the 42nd Annual Meeting of the American Society of Clinical Oncology (abstract 7018). Dr. Nemunaitis is executive medical director of the Mary Crowley Medical Research Center, which is located within the Baylor University Medical Center in Dallas, Texas.

An Attractive Target

TGF-β2 is an attractive target for cancer therapy, Dr. Nemunaitis said, because it is produced by cancer cells and inhibits multiple parts of the anti-tumor immune response system, including T and B lymphocytes, activation of antigen-presenting cells, natural killer cell function, and interferon-gamma production by immune effector cells. It also induces FoxP3 expression and stimulates Tregulatory cell generation.

Lucanix is a TGF-β2 antisense gene-modified allogeneic tumor cell vaccine. It enhances tumor antigen recognition by inhibiting TGF-β2. No viral vector is required, and the vaccine is given by monthly injection. The agent is being developed by NovaRx Corporation, San Diego, California.

Dr. Nemunaitis reported the results of a phase II study of Lucanix in 75 NSCLC patients (2 stage IIB, 12 stage IIIA, 14 stage IIIB, 47 stage IV). All of the advanced-stage patients had received extensive prior chemotherapy. Patients were randomized to three dose levels of the vaccine (1.25, 2.5, 5.0 × 10

⁷

cells/injection) given intradermally, to a maximum of 16 injections, either monthly or every other month. The main toxicity was local (grade 1) erythema. There were no grade 3 or worse adverse events related to the vaccine.

Dose-Reponse Seen

Dr. Nemunaitis reported a 15% response rate to the vaccine (partial response and stable disease), and a dose-response effect. Survival was longer in patients who received more than 2.5 × 10⁷ cells/injection, compared with those who received 2.5 × 10⁷ cells/injection or less (P = .0155).

In the stage IIIB-IV patients, survival at 1 year was 61% in the high-dose group vs 40% in the low-dose group, and at 2 years, 52% and 13%, respectively. By comparison, historical data of studies of stage IIIB-IV NSCLC patients show 1-year survival of 18% to 19% with placebo, 28% with erlotinib (Tarceva), 29% to 30% with docetaxel (Taxotere), and 30% with pemetrexed (Alimta), Dr. Nemunaitis said.

Dr. Nemunaitis also showed that, at week 12, immunologic activity induced by the vaccine was significantly greater in responding patients than in those with progressive disease.

"Lucanix administered at a dose of 2.5 × 10⁷ cells/injection or more is felt to be optimal, based on the high safety profile and suggestion of greater survival duration in comparison to historical standard of care. Phase III investigation is justified, given the high level of safety of this vaccine," Dr. Nemunaitis concluded.

During the discussion period, Dr. Nemunaitis said that a phase III trial was scheduled to begin in November that would compare Lucanix to pemetrexed in patients with advanced NSCLC.