In an early-stage clinical trial with a handful of patients, Lyell Immunopharma’s experimental CAR-T therapy for solid tumor cancers showed hints of efficacy but also faced significant safety concerns, including one death.
The company said the safety issues were limited to a subgroup of patients, and it will be adjusting the trial moving forward to mitigate those concerns.
In 16 patients who received Lyell’s CAR-T cell therapy LYL797 and were evaluated for efficacy, six achieved stable disease or a partial response, according to results shared Wednesday. These were patients who had either triple-negative breast cancer — a less common but aggressive form of breast cancer — or lung cancer.
Lynn SeelyAt the highest dose so far — 150 million cells — two of five patients saw their tumors shrink by at least 30%, constituting a partial response, which was maintained to day 90 as of the May 29 data cutoff. Lyell’s CEO Lynn Seely told Endpoints News on Tuesday that a key positive signal was the dose dependency of the responses — as the dose got higher, so did the percentage of tumor shrinkage.
But the therapy also came with notable safety concerns. One patient who received the 150 million cell dose — not one of the two who responded — died from respiratory failure on day 41. Three other patients also experienced grade 3 or higher hypoxia or pneumonitis, which is lung inflammation, deemed related to treatment.
The patients who experienced these toxicities had breast cancer that had metastasized to their lungs, according to the company. “There is more to be learned,” Seely said. “But we believe that with dexamethasone prophylaxis, we have a strategy where we can dose-escalate.”
The company plans to give patients steroid treatment proactively for the lung inflammation.
Lyell said it is also moving forward with different doses depending on whether patients’ cancers impact their lungs. In those patients with no “lung involvement,” Lyell plans to move ahead with testing a 300 million cell dose, while in those with “lung involvement,” it plans to test a 75 million cell dose.
The solid tumor challenge
Despite their transformative impact on blood cancers, CAR-T cell therapies have struggled to produce similar results in solid tumors. In those cancers, researchers have found that CAR-T cells get exhausted quickly — meaning they lose their killing abilities. Lyell engineers its cell therapies in hopes of preventing that.
It’s one of several companies trying to get CAR-T cell therapies to work for treating solid tumors. At ASCO earlier this month, AstraZeneca and Chinese partner AbelZeta reported promising early results on a CAR-T therapy in liver cancer, showing that over half of patients responded.
Lyell’s therapy targets ROR1, a protein found abundantly in a range of solid tumors and blood cancers.
The company also has a second ROR1-targeting cell therapy in the works that it hopes can be dosed at a lower level, Seely said. It has filed an application with the FDA to start running a clinical trial for that treatment.
When asked if the biotech would eventually select one of the two candidates to push forward, Seely said, “We’ll be making data-driven decisions. But in the meantime, we’re going to move them both forward in parallel.”
Lyell was founded by former National Cancer Institute director Rick Klausner and saw much fanfare in its early days. When Lyell listed on the Nasdaq in 2021, the company was valued at more than $4 billion, but it has since sputtered out. The company’s shares $LYEL currently sit at around $2, down 87% from when it first listed on the Nasdaq.