Merck, Targovax Team Up for New Mesothelioma Clinical Trial

Standard-of-care treatment for malignant mesothelioma could change significantly, depending upon the results of an upcoming clinical trial of two immunotherapy agents used in combination with chemotherapy.

The mesothelioma clinical trial will involve pembrolizumab, also known by the brand name Keytruda, and its synergy with ONCOS-102, a lesser-known, genetically modified adenovirus.

Individually, both have shown modest efficacy for mesothelioma patients when used with chemotherapy. Together, there is potential for a much greater impact in significantly extending patient survival.

The clinical trial is a partnership between Targovax, a small Scandinavian biotech company that produces ONCOS-102, and the pharmaceutical company Merck & Co. Inc., which manufactures Keytruda.

“We could end up with a very powerful immunotherapy combination,” Dr. Magnus Jaderberg, chief medical officer at Targovax, told The Mesothelioma Center at Asbestos.com. “Standard of care will likely change in the next couple years. There is a good chance ONCOS-102 could be part of that.”

Synergy of Mesothelioma Treatments Critical

First-line standard of care for pleural mesothelioma patients today — intravenous use of pemetrexed (Alimta) and cisplatin chemotherapy — has not changed for almost two decades, limiting patients to a median 12-month overall survival rate.

In 2019, the U.S. Food and Drug Administration did approve the use of Tumor Treating Fields, which utilizes low-voltage electrical fields, but its use has been limited.

The FDA also approved Keytruda for mesothelioma in 2020, but only for the small percentage of patients expressing high levels of PD-L1, a particular cell-surface protein, and whose previous treatments have failed.

Adding ONCOS-102 to the mix could make Keytruda considerably more effective and dramatically expand the percentage of mesothelioma patients for which it would work.

Earlier studies of ONCOS-102 have shown that it increases the expression of PD-L1 and sparks a more robust immune system activation, making T cells more effective in destroying tumor cells.

ONCOS-102 is expected to increase a tumor’s sensitivity to Keytruda.

“With mesothelioma, there is a massive need for a new treatment that can provide a better long-term outcome for patients,” Jaderberg said. “We are interested in addressing that medical need based on the scientific data we’ve produced over the last five years. The data points to a potential benefit with this combination.”

Earlier Studies of ONCOS-102 Encouraging

A small, randomized clinical trial recently compared the use of ONCOS-102 with standard chemotherapy in contrast to standard chemotherapy alone.

The combination produced a progression-free survival rate of 8.9 months. That is compared to 7.6 months for chemotherapy alone in previously untreated patients, the indication Targovax is now targeting for further development.

It also produced a 12-month survival of 64%, compared to a 50% survival rate for just chemotherapy.

Patients who received ONCOS-102 had significantly more immune activation, the basis for an effective immune therapy.

Another clinical trial, which was reported at the recent American Society of Clinical Oncology 2020 meeting, showed a 12-month survival of 70% when using standard chemotherapy in combination with durvalumab, a drug very similar to pembrolizumab. Progression-free survival was similar to chemotherapy alone.

Jaderberg’s belief is that the complementary biological mechanism — the synergy — of ONCOS-102 and drugs such as pembrolizumab or durvalumab will provide even better clinical benefit than either did alone with chemotherapy.

Drugs such as these are known as checkpoint inhibitors, which all may be strengthened by ONCOS-102.

Upcoming ONCOS-102 Clinical Trial Much Larger

From a safety standpoint, ONCOS-102 was well tolerated in the latest trial, showing no side effects beyond what is typically seen with chemotherapy.

ONCOS-102 also is being studied in clinical trials for use with prostate cancer, ovarian cancer and melanoma.

Jaderberg said he expects the upcoming trial will include at least 100 patients throughout the U.S. and Europe with at least 10 centers participating within the U.S.

The randomization will compare pembrolizumab, chemotherapy and ONCOS-102 against pembrolizumab and chemotherapy alone.

Two other ongoing clinical trials with previously untreated patients and immunotherapy drugs are being closely watched by the mesothelioma community.

Bristol-Myers Squibb is studying the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), and comparing it to chemotherapy alone.

A Canadian network trial is comparing pembrolizumab plus chemotherapy with chemotherapy alone. Results from both trials are expected in 2021, and also could change standard-of-care treatment.

“Until we have the latest data, we don’t want to be overconfident,” Jaderberg said. “But we’ve had some good signals so far. We’ll call them signals of efficacy that has given us, and Merck, the confidence to move forward without delay.”

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