DUBLIN – Shares in Targovax ASA surged almost 40 percent to an all-time high Thursday on preliminary top-line data indicating a possible survival benefit in pancreatic cancer for its peptide-based therapeutic vaccine TG01, in development for Ras-mutated cancers.

The Oslo, Norway-based firm reported that 68 percent (13/19) patients were still alive two years after undergoing resection and subsequent therapy in an open-label phase I/II trial. That number dropped to 12/19 of patients (63 percent) if survival was timed from the initiation of therapy, which occurred on average about two months after surgery.

For comparison purposes, the firm pointed to historical two-year survival rates ranging from 30 percent to 53 percent for resected patients treated with gemcitabine only. The company added a heavy qualification to its own data, because of the small size of the cohort and the uncontrolled nature of the phase I/II trial.

In its favor, between 65 percent and 100 percent of patients in the historical comparator trials were designated R0, meaning that their tumors were completely removed during surgery. "Only one-third of our patients that were treated had their tumors completely removed," Targovax's chief medical officer, Magnus Jaderberg, told BioWorld Today. The survival difference between complete and partial tumor resection is significant, so a TG01-mediated immune response is one obvious explanation for the survival rates seen.

Establishing a correlation between survival and patients' T-cell responses is an important link in the evidential chain, therefore. Those analyses have not yet been completed. "We are doing a complete review, a qualitative and quantitative assessment of T cells before and after treatment," Jaderberg said. Two-year survival data from a second cohort of 13 patients, who received a slightly different treatment regimen, will mature about 12 months from now.

TG01 consists of seven synthetic peptides that represent the seven most common KRAS mutations found in pancreatic cancer. The vaccine, which is co-administered with granulocyte-macrophage colony-stimulating factor (GM-CSF), is designed to elicit T-helper responses directed against cancer cells carrying a KRAS mutation.

The therapeutic concept has a clinical history that long predates the formation of Targovax in 2010. The first patient was dosed as far back as 1993. The program was initially the subject of an alliance between the life sciences arm of Norsk Hydro ASA, a large industrial group, and Gustav Gaudernack at the Norwegian Radium Hospital in Oslo, who is now a clinical adviser to Targovax.

When Norsk Hydro exited the life sciences business, the program was picked up by a spinout firm, Gemvax AS, which was later acquired by Pharmexa A/S, of Copenhagen, Denmark. In both firms, however, the main emphasis was on another therapeutic vaccine for pancreatic cancer, GV1001, based on a telomerase peptide, which reached phase III trials in Europe and South Korea, but went no further. Meanwhile, a retrospective analysis of patients who had received KRAS peptide therapy uncovered a 20 percent survival benefit at 10 years among those who had an immune response to the vaccine.

"That's quite remarkable in pancreatic, even in resected pancreatic," Targovax CEO Øystein Soug told BioWorld Today. Targovax was formed to pick up the thread – and to recapitulate the original studies using the current standard of care, gemcitabine.

A second KRAS vaccine, TG02, is about to enter a phase I/II trial in colorectal cancer – it differs from TG01 in having eight peptides, covering the most common mutations in colorectal cancer.

An initial cohort of 10 patients will receive TG02 as a monotherapy. A second group of 10 patients will receive the vaccine in combination with Merck & Co. Inc.'s PD-1 inhibitor Keytruda (pembrolizumab). The main focus of the study is to understand the effect of the vaccine within the tumor microenvironment.

"We think it's important to get more detailed mechanistic data in general, in order to make intelligent development decisions," Jaderberg said.

The present incarnation of Targovax came about through the merger in 2015 of Targovax AS and Oncos Therapeutics Oy. (See BioWorld Today, June 12, 2015.)

It has an adenovirus-based oncolytic virus platform as well as its peptide vaccine technology. Its lead oncovirus program, ONCOS-102, is undergoing a series of phase I/II trials in several cancer indications. It is also collaborating with Alexander Shoushtari, of Memorial Sloan Kettering Cancer Center, in New York, on a study of ONCOS-102 plus Keytruda in patients with advanced melanoma who are refractory to immune checkpoint inhibitor therapy.

Shares in Targovax (Oslo:TRVX) peaked at NOK24.80 Thursday, before closing at NOK.24.60, a gain of 38 percent on Wednesday's close of NOK17.80.

No Comments