To give an idea of the type of CAR T therapies approved recently...

To give an idea of the type of CAR T therapies approved recently by the FDA, see Breyanzi and Tecartus below. It gives you an idea of the size of the pivotal clinical trials, the type of side effects accepted by the FDA as reasonable (when considering risk/benefit of the treatment) and the levels of response rates that are seen to be approvable.

CLTX-CAR T is being evaluated for safety in this phase I trial... and as you can see from the below, significant side effects exist for currently approved CAR T therapy. There is preclinical evidence to suggest that CLTX-CAR T is going to be better tolerated by humans, which makes it a much more likely product to be approved by the FDA if it also shows similar levels of efficacy/response rates & duration as the already approved therapies.

BREYANZI - Feb21
"Breyanzi (lisocabtagene maraleucel) On February 5, 2021, the Food and Drug Administration approved Breyanzi (lisocabtagene maraleucel) for the treatment of adult patients with relapsed or refractory large B-cell lymphomas. Breyanzi is a CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy. It consists of autologous T cells that are genetically modified to produce a CAR protein, allowing the T cells to identify and eliminate CD19-expressing normal and lymphoma cells.

The TRANSCEND clinical trial evaluated Brevanzi preceded by lymphodepleting chemotherapy, in adults with recurrent large B-cell lymphoma after at least two lines of previous therapy. Of the 192 patients evaluable for response, the overall response rate was 73% with a complete response rate of 54%. Of the 104 patients who achieved CR, 65% had remission lasting at least 6 months and 62% had remission lasting at least 9 months. The estimated median duration of response has not been reached at the time of the approval. The estimated median duration of response among patients with partial response was only 1.4 months.

Overall 79% had significant side effects including neutropenia anemia, and thrombocytopenia. Instances of any grade cytokine release syndrome (CRS) occurred in 46% of patients at a median onset of 5 days. There were neurologic events that occurred in 30% of patients and 21% of patients received tocilizumab and corticosteroids, respectively.

Patients with these types and stages of cancers were previously considered incurable and left with virtually no treatment options."

TECARTUS - Jul20
"On July 24 2020, the Food and Drug Administration (FDA) approved an immunotherapy for some patients with mantle cell lymphoma, a fast-growing cancer of the blood that has proven difficult to treat effectively.

The new treatment, a CAR T-cell therapy called brexucabtagene autoleucel (Tecartus), was approved for patients with mantle cell lymphoma that does not respond to other treatments or has recurred.

Mantle cell lymphoma arises in B cells, a type of white blood cell. Most people with mantle cell lymphoma are diagnosed with an aggressive form of the disease that has already spread.

FDA’s approval was based on a clinical trial, called ZUMA-2, that tested brexucabtagene in 60 patients with mantle cell lymphoma who had received up to five prior treatments.

In the trial, 87% of the patients responded to a single infusion of brexucabtagene, and 62% of the patients had a complete response, meaning that they no longer had signs of the disease, at least temporarily. All the patients had previously been treated with a drug that blocks the activity of BTK, a protein involved in the growth and survival of some cancers.

“Our study showed that CAR T-cell therapy has the potential to overcome the resistance of mantle cell lymphoma to other available therapies,” said Michael Wang, M.D., of the University of Texas MD Anderson Cancer Center, who led the clinical trial.

Like other CAR T-cell therapies, the drug may cause serious and potentially life-threatening side effects in some patients. These include cytokine release syndrome, which can lead to a high fever and flu-like symptoms, as well as neurologic effects, which can cause a patient to enter a comatose state.

Three of the 60 patients in the trial died as a result of treatment-related side effects, said Dr. Wang. Without the CAR T-cell therapy, Dr. Wang continued, all the patients in the study would have been expected to die of mantle cell lymphoma in less than a year.

“This therapy is a major advance for the treatment of relapsed and treatment-resistant mantle cell lymphoma and should be considered in all patients with the disease,” said Mark Roschewski, M.D., who studies lymphomas at NCI’s Center for Cancer Research and was not involved in the clinical trial.

“The approval will be critical for the care of patients whose cancers are resistant to BTK inhibitors,” Dr. Roschewski continued. “In general, these patients have a poor prognosis, and some develop a very aggressive form of the disease immediately following the use of BTK inhibitors.”