GenVec Inc announced the final results from its Phase Ib clinical trial for its lead oncology product candidate, TNFerade. The Phase Ib clinical trials of TNFerade, principally designed to assess the safety of the product candidate, were conducted at four centers around the country and involved patients with a wide variety of cancers including cancer of the pancreas, breast, lung, head and neck, skin, colon, and rectum. TNFerade showed substantial activity against a broad range of tumor types.
Clinical Observations (30 Patients Evaluable for Activity)
* Twenty-two out of thirty (22/30) patients (73 per cent) showed objective tumor shrinkage which means that their tumors shrank between 25 per cent and 100 per cent with TNFerade therapy. The objective tumor responses are classified as Complete Response (CR) 5/30 patients, Partial Response (PR) 9/30 patients and Minor Response (MR) 8/30 patients in this study.
* Four out of thirty (4/30) showed stable disease (SD).
* Four out of thirty (4/30) showed progressive disease in the injected lesion.
* The responses were durable during the follow-up period from 2 to 12 months
* Lower doses of TNFerade (4x10(to the 7th) and 4x10(to the 8th) p.u.) appeared less effective than the higher dose range (4x10(to the 9th) - 4x10(to the 11th) p.u.).
- 38 per cent of patients at the lower doses showed progressive disease, as compared to only 5 per cent of patients at the higher doses
- 55 per cent of patients showed partial or complete responses (PR/CR) at the high doses as compared to 25 per cent at the lower doses
- There were no CRs at the lower doses, but 23 per cent of the patients at higher doses showed complete responses.
* Tumor responses were independent of histology or tumor site.
* Three out of four (3/4) patients with pancreatic cancer at the higher dose levels showed tumor shrinkage (2 PRs, 1 MR). One patient who has been followed for 18 months showed no disease progression.
* Some patients had control lesions, which received the same radiation dose, but did not receive TNFerade. A differential effect was found in tumors receiving higher TNFerade doses plus radiation versus tumors receiving radiation only, supporting that the tumor response in these patients was due to the combination of TNFerade plus radiation, rather than radiation alone.
Safety Findings (33 Patients Evaluable for Safety)
* TNFerade was well tolerated
* No dose-limiting toxicities (DLT) seen
* No drug-related Serious Adverse Events (SAE) seen
* Serum-TNF levels were not significantly elevated
* No adenovirus detected in blood or urine of patients
* Side effects were all classified as mild.
TNFerade delivers the human tumor necrosis factor alpha (TNF-alpha) gene directly to tumors, using GenVec's proprietary adenovector gene delivery technology. Once inside the tumor, standard radiation therapy triggers a "switch" known as the EGR-1 promoter increasing the localized production of the therapeutic anticancer protein, TNF-alpha.
"We are encouraged by the safety profile of TNFerade, indicating that GenVec's approach of local delivery of TNFerade allows us to potentially harness the well-known anticancer activity of TNF-alpha without the systemic toxicity, which in the past has limited its use," stated Henrik Rasmussen, Senior Vice President of Clinical Research & Regulatory Affairs for GenVec Inc. Dr. Rasmussen continued, "Objective tumor shrinkage in 73 per cent of the patients treated in a Phase I study in solid tumors is encouraging. TNFerade appears to have broad-spectrum activity across a large number of tumor types, including tumor types which do not typically respond well to radiation therapy, such as sarcoma, pancreatic cancer and large melanomas."
Dr. Rasmussen explained, "The dose response observed, the differential effect between TNFerade plus radiation as compared to radiation alone in patients with control tumors, and the effect in tumor types not normally sensitive to radiation suggests that the effect seen is more than what would be expected by radiation alone. We have recently begun a randomized controlled Phase IIb study in patients with locally advanced pancreatic cancer and have plans to begin a second Phase II trial in patients with non- metastatic esophageal cancer to further evaluate this promising approach. Additionally, because TNFerade administration does not appear to add significant toxicity, it is well-suited as a potential combination therapy with other front line treatment modalities."
The Phase Ib clinical trials for TNFerade in solid tumors were conducted at the Albert Einstein College of Medicine, Montefiore Medical Center in New York; the University of Kentucky Medical Center, Lexington; US Oncology in Dallas, Texas, and University of South Florida Medical Center, Tampa and include patients who have failed standard treatment and who are scheduled to receive radiation therapy for local tumor control. TNFerade is injected directly into the tumors one or two times per week for up to 6 weeks, while patients are receiving their standard radiation therapy. Seven dose levels were tested with 3-6 patients at each dose level.
Cancer is the second leading cause of death in the United States. Approximately 1.2 million new cases are diagnosed in the United States each year, responsible for more than 500,000 deaths per year.