Background
3-part open-label phase 1/2 study; previously treated EGFR exon20 insertion+ metastatic NSCLC. Primary cohorts: platinum-pretreated (PPP, n=114) and EXCLAIM (n=86).
Interventions and follow up
Treatment: Mobocertinib 160 mg PO daily until progression or unacceptable toxicity
Primary endpoint: Confirmed ORR by independent review committee (IRC)
mFollow up: 13–14mo
Primary endpoint: Confirmed ORR by independent review committee (IRC)
mFollow up: 13–14mo
Results
ORR (IRC): 28% (PPP) vs 25% (EXCLAIM)
mDOR: 17.5mo vs NR
mPFS: 7.3mo vs 7.3mo
mOS: 24.0mo vs NR
mDOR: 17.5mo vs NR
mPFS: 7.3mo vs 7.3mo
mOS: 24.0mo vs NR
Adverse events
Any-grade TRAEs: diarrhea 91%, rash 45%, paronychia 38%, decreased appetite 35%, nausea 34%.
Grade ≥3: 47% overall; most commonly diarrhea 21% and rash.
Management: dose reductions 25%, discontinuation 17%; QTc prolongation requires monitoring.
Grade ≥3: 47% overall; most commonly diarrhea 21% and rash.
Management: dose reductions 25%, discontinuation 17%; QTc prolongation requires monitoring.
Conclusions
Mobocertinib produced confirmed ORR 28% with mDOR 17.5mo and mOS 24.0mo in platinum-pretreated EGFR exon20 insertion NSCLC, an active oral option in this difficult-to-treat subset.
Key Limitations
Single-arm, no comparator; high GI/skin toxicity, QTc risk. Confirmatory phase 3 EXCLAIM-2 failed its primary endpoint.
Clinical Context
FDA accelerated approval (Sept 2021) was voluntarily withdrawn (July 2024) after EXCLAIM-2 failed to confirm benefit; no longer marketed in the US. Amivantamab remains the preferred targeted agent for EGFR exon20 insertions per ESMO.