A phase 1 clinical trial of the HER3-directed antibody–drug conjugate patritumab deruxtecan shows potential for treating patients with EGFR-mutated NSCLC.
Patients with advanced EGFR-mutated non–small-cell lung cancer (NSCLC) have a poor prognosis when EGFR tyrosine kinase inhibitors (EGFR-TKIs) and platinum-based chemotherapy fail. At the ESMO Virtual Congress 2020, researchers presented safety and efficacy results from a phase 1 clinical trial of the HER3-directed antibody–drug conjugate patritumab deruxtecan in patients with EGFR-mutated NSCLC
Patients with EGFR-mutated NSCLC and previous EGFR-TKI and platinum-based chemotherapy were enrolled in the trial. The primary objective is the assessment of activity by overall response rate as reviewed by a blinded independent central review. The secondary objective is evaluating the safety of patritumab deruxtecan administered intravenously every 3 weeks.
A total of 56 patients were evaluated for a response to 5.6 mg/kg of patritumab deruxtecan. At cutoff, 28 patients remained on treatment, and 6 of those patients had only 1 tumor evaluation. Enrolled patients had a median of 4 (range, 1-9) treatment regimens for metastatic disease. Fifty-one of the patients had received platinum-based chemotherapy prior to trial enrollment. A total of 49 patients had received osimertinib prior to trial enrollment, and the median number of EGFR-TKI treatments was 2 (range, 1-4). Twenty-seven patients had metastases of the central nervous system.
Patients were treated for a median of 3.5 months (range, 1-14 months) with a median follow-up of 5.4 months (range, 0.3-15 months). Decreased platelet counts (25%) and decreased neutrophil counts (16%) were the most common treatment-induced adverse events with a grade ≥3 rating.
Nearly all tumors had HER3 expression. Patients had various EGFR-TKI resistance mechanisms, including EGFR C797S mutation, MET amplification, HER2 mutation, BRAF fusion, and PIK3CA mutation. Patients with these various EGFR-TKI resistance mechanisms showed a response to patritumab deruxtecan treatment.
The authors concluded that patritumab deruxtecan showed promise as a safe and effective treatment in patients with advanced or metastatic EGFR-mutated NSCLC that failed EGFR-TKI or platinum-based treatments.
Yu HA, et al. ESMO 2020. Abstract LBA62.