Moreover, the median PFS was 5.5 months (95% CI, 5.1-6.4) and the median OS was 11.9 months (95% CI, 10.9-13.1).Ĭonfirmed response was observed among a variety of mechanisms of EGFR TKI resistance. In this subgroup, the confirmed ORR was 29.2% (95% CI, 23.1%-35.9%), including 1 CR. Most patients received a prior third-generation EGFR TKI (93%) and 40% had prior immunotherapy.Īdditional findings from the study demonstrated that efficacy was observed across patient subgroups, including patients who were previously treated with a third-generation TKI and platinum-based chemotherapy (n = 209). In terms of prior treatments, 26% of patients had 2 prior lines and 73% having received 2 or more. The median time since initial diagnosis was 41.0 months (range, 9.1-224.7) and there were patients with brain metastasis (32%) as well as liver metastasis (33%) at baseline. L858R mutations were reported in 36% of patients. The median age was 64 years (range, 37-82), and most patients were female (59%), had an ECOG performance status of 1 (66%), a history of central nervous system (CNS) metastasis (51%), had an Ex19del EGFR-activating mutation (63%). Patients enrolled on 2 HERTHENA-Lung01 were heavily pretreated with a median of 3 prior lines of therapy (range, 1-11) and displayed adverse prognostic characteristics. DOR as evaluated by BICR represented the key secondary end point. The primary end point was confirmed ORR by blinded independent central review (BICR). Only data from the 5.6-mg/kg arm were presented. However, after a benefit-risk assessment of phase 1 data, the uptitration arm was closed. Patients were initially randomly assigned 1:1 to receive patritumab deruxtecan at a fixed dose of 5.6 mg/kg (n = 225) or via an uptitration dosing schedule (n = 50). Patients with inactive or previously treated asymptomatic brain metastases were allowed. Treatment with a prior EGFR TKI and platinum-based chemotherapy was required, as was pretreatment tumor tissue. The pivotal HERTHENA-Lung01 trial enrolled patients with advanced EGFR-mutated NSCLC who experienced disease progression on their most recent systemic therapy. The regulatory decision was based on findings from the phase 1 U31402-A-U102 study (NCT03260491), which showed that the ORR was 39% (95% CI, 26%-52%) among patients who received the agent at a dose of 5.6 mg/kg (n = 57). Patritumab deruxtecan previously received breakthrough therapy designation from the FDA in December 2021 for the treatment of patients with metastatic or locally advanced EGFR-mutated NSCLC who experienced disease progression on or after treatment with a third-generation TKI and platinum-based therapies. 3 “The clinically meaningful efficacy observed across a broad range of HER3 expression and diverse mechanisms of EGFR TKI resistance as well as the antitumor activity seen in patients with brain metastases, underscore the potential of patritumab deruxtecan to become an important treatment option for a population of patients with lung cancer who have limited treatment options.” Yu, MD, a thoracic oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York, New York, said in a news release. “The results from HERTHENA-Lung01 provide compelling evidence of efficacy of patritumab deruxtecan in heavily pretreated patients with advanced EGFR-mutated NSCLC,” Helena A. The median progression-free survival (PFS) was 5.5 months (95% CI, 5.1-5.9) and the median overall survival (OS) was 11.9 (95% CI, 11.2-13.1). The confirmed overall response rate (ORR) was 29.8% (95% CI, 23.9%-36.2%) among all patients who received a previous EGFR TKI and platinum-based chemotherapy (n = 225), including 1 patient who achieved a complete response (CR). Patritumab deruxtecan (HER3-DXd), a HER3-directed antibody-drug conjugate, led to clinically meaningful and durable efficacy among patients with advanced EGFR-mutated non–small cell lung cancer (NSCLC) whose disease had progressed on treatment with an EGFR-directed TKI and platinum-based chemotherapy, according to findings from the phase 2 HERTHENA-Lung01 trial (NCT04619004) presented during the 2023 World Conference on Lung Cancer and simultaneously published in the Journal of Clinical Oncology.
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