Imfinzi Plus Ceralsertib Addresses ‘Major Unmet Need’ in Lung Cancer

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An immunotherapy-targeted therapy combination could offer a new treatment option to patients with non-small cell lung cancer whose tumors have become resistant to other treatments.

A two-drug combination is showing promise in certain patients with non-small cell lung cancer.

In patients with non-small cell lung cancer (NSCLC), treatment with ceralasertib, a type of targeted therapy, plus Imfinzi (durvalumab) has been shown to boost the immune system and improve outcomes when tumors become resistant to other treatments, according to a findings from the HUDSON trial published in the journal Nature Medicine.

These findings are important for patients to know because this combination may open up a “new treatment option” for patients whose tumors became resistant to chemotherapy and immunotherapy, according to Dr. John Heymach, study author and chairman of thoracic and head neck medical oncology at The University of Texas MD Anderson Cancer Center.

“Our biggest unmet need is what to treat patients with once they've exhausted chemotherapy and immunotherapy. So that's one major unmet need that this [drug combination] addresses,” Heymach said during an interview with CURE®.

“Now, it also addresses a need [for] patients with ATM mutations, and it's about 10% a lung cancer. And up to this point, we had no specific therapies that could help them,” he added. “So even though this may be generally helpful for the lung cancer population, it may be especially helpful for this smaller group that has ATM mutations where this could be an even more effective therapy.”

The phase 2 HUDSON trial included 268 patients: 88 patients were included in biomarker-matched cohorts, 77 were in the primary biomarker-nonmatched cohort and 103 were in the acquired resistance biomarker-nonmatched cohort.

Having a biomarker-matched cohort, Heymach defined, is when researchers think a specific biomarker in a group of patients will match a certain drug. Conversely, a biomarker-nonmatched cohort is when patients are randomly sorted into different groups to receive different treatments, he said.

Patients were placed into 12 treatment arms that included Imfinzi or ceralsertib in each regimen, according to a listing on ClinicalTrials.gov, in which 79 patients received the Imfinzi-ceralsertib combination and 189 patients received the other regimens, the study stated.

For patients who had ATM-mutated NSCLC, researchers determined that inhibiting a protein called ATR with ceralsertib could stop the growth of the tumor.

“ATM and ATR are partners, and they can compensate for each other in helping a tumor repair DNA damage. So the idea is that if ATM is broken, that tumor may really depend on ATR. And if you block ATR, then the tumor has no alternative,” Heymach explained.

He noted that data from patients who received ceralsertib in nonmatched cohorts demonstrated that it worked, which he and other researchers did not expect, specifically for tumors that had previously suppressed the immune system.

“We call these immunologically cold tumors. And what it did was turn immunologically cold tumors hot, so we could, from monitoring the blood, see that this drug really managed to reanimate or activate the immune system to attack the tumors,” Heymach said. “That was a surprise to see that so we really learned a lot from the study.”

In terms of advice for patients with NSCLC, Heymach advised speaking with their providers about other treatment options besides chemotherapy and immunotherapy and to consider participating in clinical trials.

“We have so many exciting new types of therapies now that would only be available through clinical studies,” he said. “And that's also what makes progress for the whole field.”

Heymach emphasized that patients should have their tumors appropriately analyzed with genomic profiling by their lung cancer specialists to receive the best care and noted that speaking with a lung cancer specialist who is familiar with different subgroups of lung cancer is crucial, because “all the [possible drug] options can make a big difference.”

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