Trastuzumab deruxtecan

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

All 91 patients were evaluable for response. The confirmed objective response rate was 55% (95% CI, 44%–65%), including one complete response (1%). The median DOR was 9.3 months (95% CI, 5.7–14.7). Disease control was observed in 92% of patients (95% CI, 85%–97%).

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

The median PFS was 8.2 months (95% CI, 6.0–11.9), and the median OS was 17.8 months (95% CI, 13.8–22.1).

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

Among 33 patients with CNS metastases at baseline, 14 had previously received radiation therapy to the brain, and 19 had not. Of these patients, 8 (57%) and 10 (53%), respectively, had a partial response. The median PFS for patients with CNS metastases at baseline was 7.1 months (95% CI, 5.5–9.8), and the median OS was 13.8 months (95% CI, 9.8–20.9).

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

Grade 3 or higher drug-related adverse events occurred in 46% of patients. The most common adverse events were nausea, fatigue, alopecia, vomiting, neutropenia, anemia, diarrhea, decreased appetite, leukopenia, and constipation. The most common grade 3 or higher drug-related adverse events were neutropenia (19%) and anemia (10%).

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

Drug-related adverse events led to treatment discontinuation in 23 patients (25%) and included pneumonitis in 12 patients (13%) and interstitial lung disease in 5 patients (5%).

DESTINY-Lung01 (NCT03505710) was a multicenter, open-label, two-cohort, phase II clinical trial that investigated trastuzumab deruxtecan at a dose of 6.4 mg/kg of body weight. Enrolled patients had unresectable or metastatic nonsquamous NSCLC with disease relapse during standard treatment or with disease that was refractory to standard treatment. Patients had HER2 variants or HER2-overexpressing disease. Patients who had previously received a HER2 antibody or an antibody-drug conjugate were ineligible. However, those who had received a HER2 TKI were eligible. The primary end point was objective response as assessed by independent central review. Ninety-one patients with NSCLC and HER2 variants were enrolled; 95% had received previous platinum-based therapy, and 66% had received anti-PD-1 or anti-PD-L1 immunotherapy.[61][Level of evidence C3]

There were two drug-related deaths caused by interstitial lung disease.