Takeda Voluntarily Withdraws Exkivity as Treatment for NSCLC Subset

Takeda announced that it will be working with the Food and Drug Administration (FDA) to voluntarily withdraw the tyrosine kinase inhibitor Exkivity (mobocertinib) in the U.S. for adults with epidermal growth factor receptor (EGFR) exon 20 insertion mutation-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who progressed on or after platinum-based chemotherapy.

The decision to withdraw Exkivity from the U.S. for this indication was a result of discussions with the FDA, according to a press release from Takeda, the manufacturer of the drug. The basis of those discussions centered around findings from the phase 3 EXCLAIM-2 trial.

This confirmatory trial did not meet its primary endpoint of progression-free survival, defined as the time from the date of treatment assignment until when a patient develops progressive disease or dies, according to the trial’s listing on ClinicalTrials.gov. Missing the primary endpoint did not fulfill the confirmatory data requirements requested by the FDA for the drug’s accelerated approval.

“Our steadfast commitment to pursue solutions for people with high unmet needs led us to develop and launch Exkivity as the first oral therapy designed for patients with EGFR exon 20 insertion-(positive) metastatic NSCLC,” Dr. Awny Farajallah, head of global medical affairs oncology at Takeda, said in the release. “We have been fortunate to witness the impact Exkivity has had on this previously underserved population and are encouraged to see the advancements made since its approval to introduce new therapies for these patients. We hope that findings from the EXCLAIM-2 study will inform future research and development for this disease.”

According to the ClinicalTrials.gov listing, researchers conducting the phase 3 EXCLAIM-2 trial enrolled 354 patients with EGFR exon 20 insertion-positive, locally advanced or metastatic NSCLC to compare the efficacy and safety of Exkivity and platinum-based chemotherapy in the first-line setting (the first treatment given for a disease).

In addition to progression-free survival, researchers also measured objective response rate (the percentage of patients with a complete or partial response to treatment), overall survival (the time from the start of treatment that a patient with cancer is still alive) and duration of response (the amount of time it took for the patient to obtain a partial or complete response to treatment), among other outcomes. Side effects were also monitored throughout the trial.

There were no new safety signals observed in patients with NSCLC enrolled in the EXCLAIM-2 trial, according to the release.

Takeda urged patients who are currently receiving Exkivity to treat NSCLC to consult their health care provider for next steps.

“Takeda is committed to ensuring patients receiving Exkivity can maintain access, as appropriate and in consultation with their health care provider,” according to the release. “We are actively assessing access mechanisms with regulatory authorities.”

The company intends to issue similar voluntary withdrawals globally where the drug has been approved.

Exkivity was first approved by the Food and Drug Administration in September 2021 for the treatment of adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease progressed during or after receiving platinum-based chemotherapy. This approval marked the first oral therapy OK’d for this subgroup of patients.

In particular, Exkivity is a tyrosine kinase inhibitor, which is a treatment designed to target EGFR exon 20 insertion mutations, according to the release. Although NSCLC accounts for nearly 85% of all lung cancer cases in the world, approximately 1% to 2% of these patients will have the disease with EGFR exon 20 insertion mutations, according to the World Health Organization.

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