Patritumab Deruxtecan Meets PFS End Point in Pretreated EGFR-Mutant NSCLC

The investigational HER​​3-directed antibody-drug conjugate patritumab deruxtecan (HER3-DXd) elicited a statistically significant improvement in progression-free survival (PFS) vs platinum-based chemotherapy in patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who were previously exposed to an EGFR TKI, meeting the primary end point of the phase 3 HERTHENA-Lung02 trial (NCT05338970).¹

Overall survival data remain immature at the time of this analysis and will be further assessed as a secondary end point of the trial. Additionally, no new safety signals were reported with patritumab deruxtecan, and the agent exhibited a toxicity profile consistent with that observed in prior studies in NSCLC. Notably, interstitial lung disease (ILD) events were primarily grade 1/2, with 2 grade 5 ILD events reported.

These results will be presented at an upcoming medical meeting and submitted to global regulatory bodies.

“These results from HERTHENA-Lung02 demonstrate the potential of patritumab deruxtecan to become an important treatment option for certain patients with EGFR-mutated NSCLC with prior TKI treatment,” Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, stated in a news release. “We plan to share these findings with regulatory authorities to discuss next steps.”

“We are encouraged by these results demonstrating a statistically significant PFS improvement compared [with] platinum plus pemetrexed [Alimta] induction chemotherapy followed by pemetrexed maintenance chemotherapy in patients with locally advanced or metastatic EGFR-mutated NSCLC who received prior TKI treatment,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck, added. “Together with Daiichi Sankyo, we are committed to helping patients with previously treated EGFR-mutated NSCLC, where there is a high unmet need.”

HERTHENA-Lung02 Overview

This global, multicenter, open-label trial enrolled patients at least 18 years of age with histologically or cytologically confirmed metastatic or locally advanced nonsquamous NSCLC who harbor either an EGFR exon 19 deletion or exon 21 L858R mutation. Prior progression on or after treatment with 1 or 2 prior lines of therapy including a third-generation EGFR TKI, documented radiographic disease progression on or after receiving a third-generation EGFR TKI, at least 1 measurable lesion per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1 was also required. Patients with stable brain metastases were also allowed to enroll onto the study.^1,2

Exclusion criteria comprised a history of ILD or other clinically severe respiratory compromise; prior receipt of any systemic therapies in the metastatic or locally advanced setting other than EGFR TKIs; or significant cardiovascular disease.

A total of 586 patients have been enrolled onto HERTHENA-Lung02 across Asia, Europe, North America, and Oceania.¹ Upon enrollment, these patients were randomly assigned to receive 5.6 mg/kg of patritumab deruxtecan administered intravenously every 3 weeks in the experimental arm or 4 cycles of either cisplatin 75 mg/m² or carboplatin at a target area under the curve 5 plus 500 mg/m² of pemetrexed every 3 weeks.²

Notably, patients in the comparator arm who did not experience disease progression after 4 cycles of treatment were permitted to continue maintenance pemetrexed with no restriction on the number of cycles.¹

The primary end point of the study is PFS by blinded independent central review. Secondary end points include OS, overall response rate, clinical benefit rate, time to response, disease control rate, and safety. Brain imaging was also conducted for the assessment of intracranial end points.

The study has an estimated completion date of August 2026.²

Ongoing Evaluation of Patritumab Deruxtecan

In December 2023, the FDA granted priority review to patritumab deruxtecan for the treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC who previously received 2 or more systemic therapies based on data from the phase 2 HERTHENA-Lung01 trial (NCT04619004).³

In addition to HERTHENA-Lung01 and HERTHENA-Lung02, patritumab deruxtecan is currently being evaluated alone or in combination regimens in several other clinical trials as part of a global development program. These include the phase 2 HERTHENA-PanTumor01 study (NCT06172478) evaluating the agent in locally advanced or metastatic solid tumors previously treated with at least 1 systemic therapy; a phase 1 trial (NCT04676477) of patritumab deruxtecan plus osimertinib (Tagrisso) in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial (NCT03260491) of the agent in previously treated patients with advanced NSCLC.¹

References

1. Patritumab deruxtecan demonstrated statistically significant improvement in progression-free survival versus doublet chemotherapy in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer in HERTHENA-Lung02 phase 3 trial. News Release. Merck. September 17, 2024. Accessed September 17, 2024. https://www.merck.com/news/patritumab-deruxtecan-demonstrated-statistically-significant-improvement-in-progression-free-survival-versus-doublet-chemotherapy-in-patients-with-locally-advanced-or-metastatic-egfr-mutated-non-small/
2. HERTHENA-Lung02: a study of patritumab deruxtecan versus platinum-based chemotherapy in metastatic or locally advanced EGFRm NSCLC after failure of EGFR TKI therapy. ClinicalTrials.gov. Updated on August 28, 2024. Accessed September 17, 2024. https://clinicaltrials.gov/ct2/show/NCT05338970
3. Patritumab deruxtecan granted priority review in the U.S. for certain patients with previously treated locally advanced or metastatic EGFR-mutated non-small cell lung cancer. News release. Merck. December 22, 2023. Accessed September 17, 2024. https://www.merck.com/news/patritumab-deruxtecan-granted-priority-review-in-the-u-s-for-certain-patients-with-previously-treated-locally-advanced-or-metastatic-egfr-mutated-non-small-cell-lung-cancer/