Evaluate PK, Efficacy, Safety of HER3-DXd in EGFRm NSCLC: Study 1190TiP

Patients diagnosed with advanced non-small cell lung cancer (NSCLC) with a mutation in the epidermal growth factor receptor (EGFRm) face limited treatment options after their disease progresses despite being treated using platinum-based chemotherapy (PBC) and an EGFR tyrosine kinase inhibitor (TKI). HER3, a human epidermal growth factor receptor family member, is expressed in most EGFRm NSCLC and various solid tumors. Overexpression of HER3 has been linked to poor clinical outcomes, such as metastatic progression and decreased relapse-free survival. HER3-DXd is a new treatment type that combines a human anti-HER3 monoclonal antibody (patritumab) with topoisomerase I inhibitor payload through a stable tetrapeptide-based, tumor-selective, cleavable linker. The phase I trial (U31402-A-U102; NCT03260491) conducted on patients with heavily pretreated EGFRm NSCLC (including EGFR TKI; median of 4 prior lines of therapy) showed that HER3-DXd 5.6 mg/kg every three weeks (Q3W) had a manageable safety profile and promising efficacy (confirmed ORR by BICR, 39%; median PFS, 8.2 months [Jänne et al. Cancer Discov. 2022;12:74-89]).

To further evaluate the pharmacokinetics (PK), safety, and efficacy of HER3-DXd produced from commercial manufacturing sites, a fourth expansion cohort has been initiated with the enrollment of patients. This is done to extend the earlier observations and gather more data to assess the effectiveness of HER3-DXd as a treatment option for EGFRm NSCLC. This is an open-label, multicenter, phase I study that has been updated to include cohort 4, consisting of approximately 45 patients who have locally advanced or metastatic non-small cell lung cancer (NSCLC) with an EGFR mutation and have progressed despite being treated with EGFR TKI therapy and at least one line of platinum-based chemotherapy (PBC). Patients with EGFR-activating mutations such as exon 19 deletion, L858R, G719X, and L861Q are eligible, while those with other EGFR mutations may be considered after consultation with the sponsor.

During the study, patients were treated with HER3-DXd 5.6 mg/kg every three weeks (Q3W) obtained from commercial manufacturing sites. Treatment continues until disease progression, adverse events, or other discontinuation criteria are met. The primary objective of cohort 4 is to evaluate the pharmacokinetics (PK) during the first treatment cycle. Secondary goals are evaluating HER3-DXd’s PK, safety, tolerability, immunogenicity, and effectiveness.

Source: https://oncologypro.esmo.org/meeting-resources/esmo-congress/pharmacokinetics-efficacy-and-safety-of-patritumab-deruxtecan-her3-dxd-in-egfr-inhibitor-resistant-egfr-mutated-egfrm-non-small-cell-lung-ca

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03260491

Annals of Oncology (2022) 33 (suppl_7): S448-S554. 10.1016/annonc/annonc1064