EGFR inhibitors like AstraZeneca’s Tagrisso and Genentech’s Tarceva have been on the market for years to treat patients with lung cancer. But those drugs are designed to treat patients with specific mutations, and one patient group with a rare type of EGFR mutation has fallen through the cracks. With promising phase 1/2 data, Takeda is one step closer to providing those patients with a targeted treatment.
The company’s tyrosine kinase inhibitor (TKI) curbed tumor growth in 78% of 114 patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions. It shrank tumors in 28% of the patients and staved off cancer progression for a median of seven months. Patients responded to the treatment for a median of 17.5 months.
The study tested the drug, mobocertinib, in patients whose cancer had gotten worse despite undergoing platinum chemotherapy. The data come from patients who had received a 160-mg dose of mobocertinib each day. These include those in the dose-escalation and initial expansion portions of the study—in which multiple doses were tested—as well as from the pivotal phase 2 extension group, in which 96 patients received the same 160=mg dose.
“This patient population is so desperately in need of a treatment that can specifically address that oncodriver mutation responsible for the metastatic non-small cell lung cancer,” Chris Arendt, Ph.D., Takeda’s oncology therapeutic area head, said. Patients with this type of mutation have one or more nucleotide bases—or letters—inserted in a segment of DNA called exon 20.
“It affects about 10% of patients who present with EGFR mutations, while other exons—18, 19, 21—cause different subtypes of disease,” Arendt said, adding that exon 20 insertions affect about 2% of NSCLC patients globally.
Because there is no targeted treatment for this specific mutation, patients with this type of lung cancer are treated with platinum chemotherapy.
“Some patients have been placed, historically, on other EGFR inhibitors, or in some cases, on checkpoint inhibitors, but across the board, responses to these are limited,” Arendt said.
“These are relapsed, refractory patients with essentially very little left in terms of options and we now see a majority of patients—almost 80%—getting a meaningful clinical benefit from mobocertinib,” he said.
There were no surprises in the drug’s safety profile, which mirrors what is typically seen with TKIs. As of the May data cutoff, the most common side effect was diarrhea, afflicting 90% of patients, followed by rash, affecting 45% of patients. Most side effects were mild to moderate and managed with supportive care, Arendt said.
Nineteen patients (17%) quit the study because of side effects, most commonly diarrhea (4%) and nausea (4%). Takeda has worked with investigators on a plan to manage side effects over the course of the study that went into effect toward the tail end of the phase 2 extension study.
“The good news is we have a plan going forward and also now something we can include in the prescribing information,” Arendt said. “It’s fairly simple and patient-friendly and aims to allow patients and their practitioners to be as prepared as possible to treat gastrointenstinal adverse events … as early as possible in the course of treatment.”
Takeda is not the only company working to treat patients with this particular EGFR mutation. Johnson & Johnson filed its bispecific antibody, amivantamab, for FDA approval just last month. Though J&J may snag the first approval for this patient population, its drug is given through intravenous infusion, which could give mobocertinib, an oral drug, an advantage on the convenience side.
“It can’t be understated what this can mean for the quality of life of patients. It’s easy to forget that patients live all over the map and not everyone lives close to a cancer center,” Arendt said. Oral medicines that can be delivered to patients’ homes have become even more important during a pandemic where patients may want to avoid coming into hospitals or clinics.