The American Society of Clinical Oncology (Alexandria, Virginia) wasn't the only medical association unveiling cancer data recently. In the shadow of the ASCO behemoth, the American Society of Gene Therapy's (Milwaukee) annual meeting featured some impressive clinical responses in melanoma, lymphoma and bladder cancer trials, as well as progress in personalized cancer treatment.

ASGT doesn't have ASCO's imposing bulk or glitzy industry presence – there are no pharma advertisements adorning the halls, and it's slim pickings for swag in the postage stamp-sized exhibit hall. And while ASCO enjoys mainstream prestige, the gene therapy field has struggled for a decade to overcome the negative stigma following the death of Jesse Gelsinger, not to mention subsequent questions regarding vector toxicity.

There are no gene therapy treatments approved by the FDA, but the few nearing the finish line – along with most of the field's industry support – are focused on cancer.

Last year, some thought Introgen Therapeutics' (Austin, Texas) gene therapy Advexin for head and neck cancer might become the first to gain FDA approval. But a Phase III trial failed to statistically improve survival compared to comparator drug methotrexate in the intent-to-treat population, and the FDA refused to file Introgen's biologics license application.

At ASGT, John Nemunaitis, oncologist and medical director of the Mary Crowley Medical Research Center (Dallas), explained that Advexin is a modified adenovirus that replaces the p53 gene, a tumor suppressor that is often mutated in cancer.

A subset analysis from the Phase III trial revealed that patients with a favorable p53 biomarker mutation analysis had median survival of 7.2 months, while those with an unfavorable biomarker analysis survived an average of 2.7 months. Within the favorable population, Advexin's 7.2-month survival beat 4.3 months for methotrexate.

Although details about the FDA's refusal to file the Advexin BLA were scant, Nemunaitis said the agency wanted another trial. Introgen subsequently filed for Chapter 11 bankruptcy protection, but Nemunaitis said some potential acquirers are "circling around" Advexin.

Another late-stage gene therapy player to present at ASGT was BioVex (Woburn, Massachusetts), which presented updated Phase II melanoma data on OncoVEX, a modified herpes simplex virus delivering the gene for granulocyte macrophage colony-stimulating factor. Median overall survival in the trial was 16 months, with 61% of the 50 patients surviving at least one year. There were eight complete responses, five partial responses, and the drug was well-tolerated. A Phase III trial started in April.

Other clinical oncology data garnering attention at ASGT included findings presented by Baylor College of Medicine (Houston) and others regarding 25 lymphoma patients treated with adenovirus vector-based, LMP-targeted gene therapy following chemotherapy. The treatment was well-tolerated and 12 of 13 high-risk relapsed patients remained in remission for a median of two years after treatment. At the time of treatment, 10 of 12 patients had clinical responses (eight complete and two partial), the median duration for which was 1.5 years.

A separate open-label Phase I trial showed Schering-Plough's (Kenilworth, New Jersey) adenovirus vector-based interferon gene therapy for bladder cancer was well-tolerated and induced complete remission in seven of 14 patients at three months. One patient's remission has lasted more than a year; the trial is ongoing.

More interesting data came from a team led by University of Washington (Seattle) researchers, who showed in pre-clinical studies that treatment with adenovirus-based gene therapy with high affinity for CD46 resulted in removal of CD46 from cancer cells and increased sensitivity to Rituxan – rituximab, from F. Hoffmann-La Roche (Basel, Switzerland) and Biogen Idec (Cambridge, Massachusetts). The researchers said the approach was more efficient than monoclonal antibodies or siRNA against CD46 and could be used to increase sensitivity to other antibodies.

Nemunaitis also presented findings on research into why two patients with the same type of cancer, at the same stage, receiving the same treatment can have very different responses. He said research indicates that the histology of the tumor matters much less than the different genomic signals.

At the Mary Crowley Medical Research Center, physicians often analyze biomarkers within their patients' tumors to drive better treatment decisions, he said, echoing a trend toward personalized cancer treatment emphasized earlier this year at the American Association for Cancer Research annual meeting.

At AACR, Translational Genomics Research Institute (Phoenix) scientist Daniel Von Hoff used molecular profiling from Caris Diagnostics Inc. to drive treatment decisions for 66 relapsed and refractory cancer patients, resulting in improved progression-free survival for 18 patients.

Nemunaitis has started his own company, Gradalis, to develop a liposomally-delivered RNAi approach targeting three common genomic signals associated with various cancers. He plans to advance them into the clinic individually and then as a triplexed therapy, but as to whether the FDA will let him pursue a histology-agnostic approach, he said the agency is "not there yet."