HERTHENA-Lung01, Phase II Trial of HER3-DXd in EGFR鈥揗utated NSCLC After EGFR TKI Therapy and Platinum-Based Chemotherapy

鈥� An ASCO Reading Room selection

February 23, 2024

Helena A. Yu, MD, Yasushi Goto, MD, Hidetoshi Hayashi, MD, PhD, Enriqueta Felip, MD, PhD, James Chih-Hsin Yang, MD, PhD, Martin Reck, MD, PhD, Kiyotaka Yoh, Se-Hoon Lee, MD, PhD, Luis Paz-Ares, MD, PhD, Benjamin Besse, MD, PhD, Paolo Bironzo, MD, PhD, Dong-Wan Kim, MD, PhD, Melissa L. Johnson, MD, Yi-Long Wu, MD, Thomas John, PhD, MBBS, FRACP, Steven Kao, PhD, MBChB, BHB, FRACP, Toshiyuki Kozuki, MD, PhD, Erminia Massarelli, MD, PhD, MS, Jyoti Patel, MD, Egbert Smit, MD, PhD, Karen L. Reckamp, MD, Qian Dong, PhD, Pomy Shrestha, MBBS, Pang-Dian Fan, MD, PhD, Parul Patel, MS, Andrea Sporchia, MD, David W. Sternberg, MD, PhD, Dalila Sellami, MD, and Pasi A. J盲nne, MD, PhD

Journal of Clinical Oncology

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Purpose

Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal growth factor receptor (EGFR)–mutated non–small-cell lung cancer (NSCLC).

Methods

This phase II study (ClinicalTrials.gov identifier: ) was designed to evaluate HER3-DXd in patients with advanced EGFR-mutated NSCLC previously treated with EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy (PBC). Patients received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks or an uptitration regimen (3.2 → 4.8 → 6.4 mg/kg). The primary end point was confirmed objective response rate (ORR; RECIST 1.1) by blinded independent central review (BICR), with a null hypothesis of 26.4% on the basis of historical data.

Results

Enrollment into the uptitration arm closed early on the basis of a prespecified benefit-risk assessment of data from the phase I U31402-A-U102 trial. In total, 225 patients received HER3-DXd 5.6 mg/kg once every 3 weeks. As of May 18, 2023, median study duration was 18.9 (range 14.9-27.5) months. Confirmed ORR by BICR was 29.8% (95% CI 23.9-36.2); median duration of response 6.4 months; median progression-free survival 5.5 months; and median overall survival 11.9 months. The subgroup of patients with previous osimertinib and PBC had similar outcomes. Efficacy was observed across a broad range of pretreatment tumor HER3 membrane expression levels and across diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain metastases at baseline (n = 30), the confirmed CNS ORR by BICR per CNS RECIST was 33.3% (95% CI 17.3-52.8). The safety profile (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) was manageable and tolerable, consistent with previous observations.

Conclusion

After tumor progression with EGFR TKI therapy and PBC in patients with EGFR-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in EGFR-mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: ).

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HERTHENA-Lung01, Phase II Trial of HER3-DXd in EGFR鈥揗utated NSCLC After EGFR TKI Therapy and Platinum-Based Chemotherapy

Primary Source

Journal of Clinical Oncology

Source Reference:

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