Immatics spotlights more early data for TCR cell therapy in solid tumors — now let's see if it lasts

10 Oct 2022
CollaborateCell Therapy
Almost a year after Immatics first took the wraps off preliminary data for its top TCR cell therapy, the biotech says the drug continues to live up to expectations.
Now that the Phase Ia dose escalation study is complete, Immatics has treated five patients with IMA203 in the Phase Ib at what it believes is the optimal dose, complete with improved manufacturing and study design.
Immatics unveils promising, early-stage data for a top contender in the race to develop TCRs. Now it has to live up to expectations
And that, according to the biotech, boosted the confirmed objective response rate to 80% — which, if sustained, would mark a landmark success for the quest to develop cell therapies for solid tumors.
The biotech, based in Germany with a big office in Houston, saw its shares climb almost 11% to about $11. But it didn’t exactly wait for the reaction to drop the announcement that it is looking to raise $110 million in a public offering.
Immatics spotlights more early data for TCR cell therapy in solid tumors — now let's see if it lasts
Preview
Source: Endpts
On a conference call with analysts, chief medical officer Cedrik Britten cautioned that Immatics isn’t claiming that 80% confirmed ORR is a final goal or can be achieved, but also offered 50% to 80% ORR as a range that the company views as meaningful and possibly commercially viable.
The key, he noted, will be the durability of response over time.
Looking across the total of 32 patients who’ve been infused with various doses and forms of IMA203 — including 27 from the Phase Ia — Immatics says the results also validate PRAME (preferentially expressed antigen in melanoma) as a multi-tumor target. IMA203 is designed to hit HLA-A*02-presented peptide, and it triggered responses against a variety of cancer types.
Britten added that on top of this candidate, his team is already testing the combination of IMA203 with a checkpoint inhibitor, as well as a second-generation product dubbed IMA203CD8, with clinical data expected later this year.
“In addition, we are excited to start a first-in-human trial with our half-life extended Bispecific against PRAME, TCER IMA402, also in 2023,” he said.
Between Phase Ia and Phase Ib, Immatics made the decision to lower the proportion of the sickest patients. While those in the Phase Ia averaged 4.2 lines of prior systemic treatment and had a “particularly high baseline tumor burden,” in Phase Ib they had a mean of 4.0 lines of prior systemic treatment and “high to moderate baseline tumor burden.”
Compared to Phase Ia, it also applied higher doses, optimized the manufacturing process and shifted the focus from measuring objective response rate at week 6 (“initial” ORR) to week 12 (“confirmed” ORR).
In Phase Ia, the initial ORR was 48% among all 27 patients, some of whom received low doses that are not expected to trigger a response. Confirmed ORR dropped to 19%. Zeroing in to the seven patients who received higher doses, initial ORR was 57% and confirmed ORR was 29% (2/7).
In Phase Ib, the four patients who experienced an initial response also went on to record responses at week 12, and they each had different tumors: cutaneous melanoma, ovarian cancer, uveal melanoma and head and neck cancer.
All told, if you just look at the 12 patients who got the target dose or above of at least 1 billion infused TCR-T cells, the confirmed objective response rate would be 50%, Immatics noted.
Immatics reported that almost all patients (31, or 97%) experienced cytokine release syndrome, including two patients in Phase Ia who had Grade 3 CRS. Britten noted that the CRS “kicks in pretty quickly” and, with the help of drugs like Actemra, resolves quickly. Five patients also experienced a low to moderate “immune effector cell associated neurotoxicity syndrome,” or ICANS, a side effect that’s been reported in other solid tumor trials for CAR-T.
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