New data from the phase 1/2 trial of Mobocertinib orally administered in previously treated patients with epidermal growth factor receptor ( EGFR ) exon20 insertion+ metastatic non-small cell lung cancer ( mNSCLC ) were presented at the International Association for the Study of Lung Cancer ( IASLC ) 2020 World Conference on Lung Cancer ( WCLC ).
Mobocertinib has demonstrated clinically meaningful responses and a noteworthy duration of response in patients with EGFR exon20 insertion+ mNSCLC who received prior Platinum-based therapy.
The analysis of Platinum-pretreated patients has included patients with EGFR exon20 insertion+ mNSCLC who received prior Platinum therapy from the phase 1/2 trial. All patients were treated at the 160 mg once daily oral dose.
Key findings from this population ( n=144 ) were:
a) confirmed objective response rate ( ORR ) per investigator: 35% ( 40/114; 95% CI 26-45 ); confirmed ORR per IRC: 28% ( 32/114; 95% CI 20-37 );
b) median duration of response ( DoR ) per IRC: 17.5 months ( 95% CI 7.4-20.3 );
c) median progression-free survival ( PFS ) per IRC: 7.3 months ( 95% CI 5.5-9.2 );
d) disease control rate ( DCR ) per IRC: 78% ( 89/114; 95% CI 69-85 ).
The safety profile observed was manageable. The most common treatment-related adverse events ( TRAEs; 20% or more ) in Platinum-pretreated patients from the May data cutoff were diarrhea ( 90% ), rash ( 45% ), paronychia ( 34% ), nausea ( 32% ), decreased appetite ( 32% ), dry skin ( 30% ) and vomiting ( 30% ).
Grade greater than or equal to 3 TRAEs ( 5% or more ) have included diarrhea ( 21% ).
Nineteen patients ( 17% ) have discontinued due to adverse effects, most commonly diarrhea ( 4% ) and nausea ( 4% ).
The safety profile from the November data cutoff was consistent with that of the May data cutoff.
The phase 1/2 trial has evaluated the safety, pharmacokinetics and anti-tumor activity of oral Mobocertinib in patients with non-small cell lung cancer.
The trial is comprised of a phase 1 dose-escalation, evaluating Mobocertinib as a monotherapy and in combination with chemotherapy, and a phase 2 expansion, which includes seven different cohorts, as well as an extension cohort, investigating the anti-tumor activity of Mobocertinib in various trial populations.
The Platinum-pretreated population analysis investigated 114 patients with EGFR exon20 insertion+ metastatic NSCLC who received prior Platinum-based therapy from the escalation and expansion phases of the phase 1/2 trial and were treated with Mobocertinib at the 160 mg once daily dose.
The phase 2 extension cohort, known as EXCLAIM, investigated 96 previously treated patients with EGFR exon20 insertion+ mNSCLC who were treated with Mobocertinib at the 160 mg once daily dose.
Non-small cell lung cancer is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization ( WHO ).
Patients with EGFR exon20 insertion+ metastatic NSCLC make up approximately 1-2% of patients with NSCLC, and the disease is more common in Asian populations compared to Western populations.
This disease carries a worse prognosis than other EGFR mutations because there are currently no FDA-approved therapies that target exon20 insertions, and current EGFR TKIs and chemotherapy provide limited benefit for these patients. Approximately 30,000 patients are diagnosed with the disease worldwide each year. ( Xagena )
Source: Takeda, 2021