Latest Mesothelioma T-Cell Clinical Trial Moves to Phase II

The most recent T-cell therapy aimed at mesothelioma cancer has advanced to phase II of the clinical trial process, with researchers exploring its effectiveness when combined with an already approved immunotherapy duet.

Investigators are studying the synergistic effect of gavocabtagene autoleucel (gavo-cel) when used with the combination of Opdivo and Yervoy, which was approved by the U.S. Food and Drug Administration in 2020 to treat mesothelioma.

Its earlier phase I results, when used alone, were impressive – 93% of patients experienced tumor regression – raising hopes for a much-needed advancement in mesothelioma treatment. The drug was formerly known as TC-210.

“This is only a baseline for further improvement,” said Garry Menzel, chief executive officer of TRC Therapeutics Inc., which is developing the drug. “We hope to push this further in the phase II strategy. We expect to see deeper and longer responses.”

The clinical trial involves four different, tough-to-treat solid tumors. It includes malignant mesothelioma, non-small cell lung cancer, ovarian cancer and cholangiocarcinoma, but only those expressing mesothelin, a cell-surface protein. It is found in several cancers, but most commonly in mesothelioma.

Study Taking Place at Top Cancer Centers

The phase II clinical trial is hoping to enroll 75 patients in the mesothelioma cohort, along with 20 for each of the other three malignancies. It will be conducted across six of the leading cancer treatment centers in the U.S. 

The disease control rate in phase I, which involved all four cancers, was 77%  with those receiving the genetically modified T cells.

Median overall survival rate and progression-free survival for the 23 mesothelioma patients was 11.2 months and 5.6 months, respectively. All patients had been heavily pretreated but had regressed.

“We saw patients with a lot of tumor burden and saw very significant tumor regression in this trial,” said Dr. Raffit Hassan, medical oncologist and senior investigator at the National Cancer Institute. “We saw a very nice response.”

Gavo-Cell Well Tolerated by Patients

Gavo-cell was generally well tolerated and side effects from the treatment have been manageable. Patients with ovarian cancer had median survival and progression-free survival of 8.1 and 5.8 months, respectively.

The mesothelioma cohort in phase II will be randomly assigned to receive either the single-agent gavo-cel,  gavo-cel with Opdivo, or gavo-cel combined with Opdivo and Yervoy. The study will allow for patients to be retreated with additional doses.

Gavo-cel’s success in phase I was particularly notable because, until recently, T-cell therapy had not shown effectiveness with solid tumors in advanced stages. Earlier success had been limited to blood cancers such as lymphoma and leukemia.

The FDA approved the first T-cell therapy for leukemia in 2017.

Modifying T Cells Becomes Personal  

T-cell therapy involves a modification of a patient’s own T cells, a type of white blood cell that is separated from the blood through a process known as leukapheresis. The modification is based upon a patient’s unique genetic profile.

It can take up to four weeks before the cells are reintroduced into the body, hopefully with an ability to identify and kill tumor cells by targeting the mesothelin protein.

Overexpression of mesothelin, the target in this clinical trial, often leads to tumor aggressiveness and cancer cell proliferation. 

To be part of the trial, patients must have received from one to five prior systemic standard-of-care therapies.

“We already have treated several in phase II,” Menzel said. “We are clearly leading the field. With mesothelioma, we are focused on developing a new, front-line setting.”