Adaptimmune Enters Uncharted Waters With SPEARHEAD-1 Trial

By Ed Miseta, Chief Editor, Clinical Leader

In January, Astellas and Adaptimmune announced a collaboration agreement whereby the two companies would work to co-develop and co-commercialize stem-cell derived CAR-T and TCR T-cell therapies. The agreement covers up to three T-cell therapies and leverages the Astellas Universal Donor Cell Platform and the Adaptimmune stem-cell derived allogeneic T-cell platform.

Due to the recent announcement, I recently spoke to Adaptimmune CEO Adrian Rawcliffe to learn more about the company’s pipeline in its entirety, the ongoing SPEARHEAD-1 trial, and being at the forefront of cell therapy trials.

Ed Miseta: What is the furthest advanced product in the Adaptimmune pipeline?

Adrian Rawcliffe: We have a cell-therapy product we are hoping to commercialize in 2022 that is currently in a Phase 2 clinical trial. The trial is called SPEARHEAD-1 and it is using ADP-A2M4 SPEAR T-cells in patients with synovial sarcoma and myxoid round cell liposarcoma (MRCLS). Synovial sarcoma is especially a devastating type of cancer that typically affects people in their early thirties. The mortality rate for these patients is around 85 percent, so it results in a significant loss of life.

Miseta: Is that considered a rare disease?

Rawcliffe: Yes. Synovial sarcoma is considered a rare and aggressive cancer. As a result, these are not very large trials. A few thousand patients in the U.S. and Europe are diagnosed each year with these types of cancer. Thus far, our treatment has shown a 50 percent response rate in patients with and a clinical benefit rate of 90 percent. That covers both responses and stable disease over a period of time. Investigators have described these results as game changing.

Miseta: Do patients have other treatment options?

Rawcliffe: Unfortunately, there is really nothing else available for them. The standard of care is a drug marketed by Novartis, which currently has a four percent response rate for synovial sarcoma. So you can see why a 50 percent response is clearly getting the attention of investigators. We have been granted Regenerative Medicine Advanced Therapy or RMAT and orphan drug designation by the FDA last year. The SPEARHEAD-1 trial is ongoing, and we hope to be able to market ADP-A2M4 for people with sarcoma in 2022.

Miseta: Are you working with CROs to get through the development process?

Rawcliffe: Yes, we are using them. Initially, we were doing almost all the trials internally. We were able to do that because the trials were not very large. That is one aspect where cell therapy trials are different from other trials. I have always believed that if you don't see a response in the first 10 patients, then you don't have a marketable cell therapy. Treatments need to be transformational in that regard. These therapies are only worth pursuing if you are seeing transformative benefits. For the Phase 1 and Phase 2 trials we were recruiting 10 to 20 patients. Those trials did not require a CRO.

Miseta: Is the SPEARHEAD-1 trial different?

Rawcliffe: It is. It is a slightly larger trial. It is designed to recruit 60 patients and we did enlist a CRO to help us through it. To date, we have recruited patients at more than 20 sites in the U.S., Canada, and Europe. When it comes to finding sites and recruiting patients, a CRO can be very helpful.

Miseta: Was it difficult to find a CRO with expertise in cell therapies?

Rawcliffe: I think the short answer is that no one has really done what we are trying to do with cell therapies in solid tumors. Therefore, there is really no one with that expertise. However, there certainly are CROs with cell therapy expertise gained from the CAR-T-cell development efforts of other sponsor companies such as Gilead. We tried to take advantage of that expertise.

Still, it’s important to note that none of that work was done in solid tumors. The interfaces with the oncology hospitals are very different in the hematological setting, where CAR-Ts are effective, than they are for solid tumors. There is a lot we must learn how to do, and the hospitals are learning along with us. That is simply a disadvantage of being at the forefront of the field. I think we are leading the pack in terms of getting cell therapies to work in solid tumors.

Miseta: Approximately 80 percent of clinical trials are in oncology. Has patient recruitment been a challenge for you?

Rawcliffe: There is certainly a lot of competition for patients, but when recruiting patients, nothing works better than efficacy results. When we released our data on patient responses in sarcoma early last year, the reaction was very positive from both physicians and patients. We saw a good uptake as soon as we released the data because patients want to be treated with therapies that they know work. We have since released similar data across four additional tumor types: liver, melanoma, head and neck, and gastroesophageal junction.

We believe these results will help patients when they look at what therapies are available and are forced to decide what therapies they want to try. I believe the progress we make will help stimulate demand for cell therapies in the solid tumor setting because it's clear this platform has the potential to work across a range of solid tumors. These results have helped with screening and enrollment in our trials since the end of last year and into this year.

Miseta: Where do you go from here?

Rawcliffe: We have shown excellent results in synovial sarcoma, and we have recently shown initial efficacy in other tumor indications. We are excited about the data we have seen so far, and these therapies have the potential to be a game changer in therapies for late-stage solid tumors. No other cell therapy treatment has been able to show these types of responses in a range of solid tumors.

We are uniquely placed to develop a cell therapy pipeline across a broad range of tumors. As you might expect, we are currently focused on the first commercial products in sarcoma in 2022. But behind that we have a very broad range of cell therapies that could bring huge potential for patients with cancer.