Immatics' cell therapy blasts solid tumors in phase 1, but durability spooks investors. Will dialing up the dose help?

Immatics has delivered evidence that its TCR-engineered cell therapies can move the needle in solid tumors, revealing 50% of heavily pretreated patients responded to its candidate despite taking less than the target dose. The challenge now? To improve the durability of the responses. 

Adaptimmune and Immatics have begun to validate the long-discussed, but previously unfulfilled, potential of TCR-Ts in recent years, pointing to a future in which the modality brings the power of cell therapies to solid tumors. Immatics took another step toward that goal this week with the release of data on 16 patients who received a TCR-T against PRAME, a protein expressed in solid cancers.

Across the first three dose cohorts, eight of the patients responded to the therapy. None of the three patients that received the lowest dose responded to the therapy, IMA203. The response rate in the second and third dose cohorts topped 60%. Immatics was taken aback by the efficacy of the doses. 

“This is still early days. We are in dose escalation, haven't reached the target dose, and we're really surprised to see responses, and to see such a high number of responses,” Cedrik Britten, M.D., chief medical officer at Immatics, said on a conference call with investors to discuss the data. 

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Immatics achieved that response rate in patients previously treated with a median of four lines of prior systemic therapy and at below its target dose, which is now being tested in a new cohort. Patients with synovial sarcoma, malignant melanoma, uveal melanoma and head and neck cancer responded to the cell therapy.

Shares in Immatics initially surged in response to the data, before falling away to close the day down. The trend may reflect shifts in opinion about the data as investors dug deeper, going past the initial response results to assess how long it took before the cancer came back. That side of the data is less impressive. 

Many of the partial responses ended within weeks. Three of the eight responses, including the two most recent, were ongoing as of the data cutoff around one month ago. The data leave scope to doubt whether IMA203 can trigger durable responses, but equally it is too early to conclude the drug has a critical limitation given Immatics is yet to present results from its target dose.

“The question is now what is going to happen with dose-level four. We believe this is a numbers game, where more cells hit just so hard that the tumor will not come back in a short time. We need to show that the higher dose level can really reach durability of a median of six months or above, in the majority of patients,” Britten said. “Dose-level four might make a huge difference.”

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Increasing the dose could result in more adverse events, but Britten is pleased with that side of the data set so far, telling investors the results “are better than expected ... as we haven't seen any of these worrisome grade 3 and 4 neurotoxicities or cytokine release syndromes.”

Immatics is now enrolling patients in the fourth dose cohort. In parallel, the biotech is preparing for a dose-expansion phase that will study IMA203 as a monotherapy and in combination with an immune checkpoint inhibitor. Immatics is also gearing up to study a CD8 twist on IMA203.