Takeda has announced that they will be voluntarily withdrawing mobocertinib for patients with EGFR exon 20 insertion mutation-positive non–small cell lung cancer.
Mobocertinib (Exkivity) will no longer be available in the United States for adult patients with EGFR exon 20 insertion mutation–positive, locally advanced or metastatic non–small cell lung cancer (NSCLC), as Takeda has announced plans to withdraw the indication.1
In September 2021, the FDA granted accelerated approval to mobocertinib for use in this patient population based on findings from a cohort of patients from a phase 1/2 trial (NCT02716116) who had received the agent at a dose of 160 mg.2 In this group, mobocertinib induced a confirmed objective response rate (ORR) of 28% (95% CI, 20%-37%) by independent review committee (IRC) assessment, with a median duration of response (DOR) of 17.5 months (95% CI, 7.4-20.3). The median progression-free survival (PFS) with the agent was 7.3 months (95% CI, 5.5-9.2) and the median overall survival (OS) was 24.0 months (95% CI, 14.6-28.8).
The decision for withdrawal, which follows discussions with the FDA, was based on the outcome of the phase 3 EXCLAIM-2 trial (NCT04129502), which failed to meet its primary end point of PFS.1 No new safety signals were observed, and full findings will be shared at an upcoming medical conference or published in a peer-reviewed journal.
Takeda shared plans to also initiate a voluntary withdrawal on a global scale where mobocertinib is currently approved. They are working with regulators in other countries where the agent is currently available to determine next steps.
“Our steadfast commitment to pursue solutions for people with high unmet needs led us to develop and launch [mobocertinib] as the first oral therapy designed for patients with EGFR exon 20 insertion–positive NSCLC,” Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, stated in a press release.1 “We have been fortunate to witness the impact [mobocertinib] 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.”
EXCLAIM-2 enrolled patients with locally advanced, recurrent, or metastatic NSCLC who had documented EGFR exon 20 insertion mutations and who had not previously received systemic therapy for their disease.3 Patients were required to have at least 18 years of age, have at least 1 measurable lesion by RECIST v1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and acceptable organ and hematologic function.4
They could not have received radiotherapy within the 2 weeks before randomization, and they must have recorded from radiotherapy-related adverse effects (AEs). Other exclusion criteria included having received a moderate or strong P450 (CYP)3A inhibitor or a moderate or strong CYP3A inducer within the 10 days prior to first study dose; a diagnosis of another primary malignancy beyond NSCLC; spinal cord compression or leptomeningeal disease; or uncontrolled hypertension.
Study participants were randomly assigned 1:1 to receive oral mobocertinib at a daily dose of 160 mg (arm A) or chemotherapy in the form of intravenous (IV) pemetrexed at 500 mg/m2 plus cisplatin at 75 mg/m2 or carboplatin at an area under the curve of 5 mg x min/mL for 4 cycles, then pemetrexed maintenance, on day 1 every 21 days (arm B).3 Treatment continued until disease progression, toxicity, or other discontinuation criteria were met.
Stratification factors included presence of central nervous system metastases at baseline (yes vs no) and race (Asian vs non-Asian).
Notably, crossover from the control arm to the investigative arm was permitted.
In addition to IRC-assessed PFS serving as the trial’s primary end point, secondary end points included IRC-assessed ORR and investigator-assessed ORR, DOR, time to response, disease control rate, PFS, OS, safety/tolerability, patient-reported outcomes, and health-related quality of life.
The study was initiated in January 2020 and included approximately 170 clinical sites throughout North America, Europe, the Middle East, and the Asia-Pacific regions.
Takeda shared that they are committed to ensuring that patients who are receiving mobocertinib can still maintain access to the drug if appropriate and in consultation with healthcare providers.1 The company will continue to evaluate the impact of the withdrawal.