Despite meeting the primary endpoint in a Phase III study, two patients treated with Merck and Daiichi Sankyo’s experimental antibody-drug conjugate died in a Phase III non-small cell lung cancer study, though the deaths have not been linked to patritumab deruxtecan.
Merck and Daiichi Sankyo on Tuesday announced that their investigational antibody-drug conjugate patritumab deruxtecan hit the primary endpoint in the Phase III HERTHENA-Lung02 study in non-small cell lung cancer.
Patritumab deruxtecan’s safety profile in the trial was consistent with what had been established in prior studies, with no new signals, according to the companies. “The majority of interstitial lung disease (ILD) events were low grade” but there were two deaths—both from grade 5 ILD events, though Tuesday’s announcement provided no causal link to patritumab deruxtecan treatment.
Without providing specific HERTHENA-Lung02 data, Merck and Daiichi Sankyo revealed that patritumab deruxtecan treatment resulted in “statistically significant improvement” in progression-free survival, compared with platinum plus pemetrexed induction chemotherapy followed by maintenance with pemetrexed. However, at the time of the interim analysis, overall survival data were not yet mature with the study continuing to follow its participants for the analysis.
HERTHENA-Lung02, an open-label late-stage trial, enrolled patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations. Patients underwent prior treatment with an EGFR tyrosine kinase inhibitor.
Merck and Daiichi will present full findings and analyses from the study at an upcoming medical meeting and will share its results with regulatory authorities “to discuss next steps,” Ken Takeshita, global head of R&D at Daiichi Sankyo, said in a statement.
“These results from HERTHENA-Lung02 demonstrate the potential of patritumab deruxtecan to become an important treatment option for certain patients with EGFR-mutated non-small cell lung cancer with prior tyrosine kinase inhibitor treatment,” Takeshita said.
Patritumab deruxtecan is an antibody-drug conjugate (ADC) composed of a fully human IgG1 monoclonal antibody that targets the HER3 protein on cancer cells, and an exatecan derivative payload, which is a topoisomerase I inhibitor that can trigger cell death. The ADC is the centerpiece of the $22 billion October 2023 agreement between the companies, which gave Merck the right to co-develop and co-commercialize three investigational ADCs for cancer.
In the Phase II HERTHENA-Lung01 study, patritumab deruxtecan elicited an overall response rate of nearly 30% in patients with EGFR-mutated locally advanced or metastatic NSCLC. This includes on complete response and 66 partial responses. At the time, median duration of response was over six months.
However, in June 2024, the FDA denied approval for patritumab deruxtecan, citing issues with a third-party manufacturing facility. The regulator did not flag problems with the ADC’s safety or efficacy data.
Tuesday’s readout comes soon after the end of the 2024 World Congress on Lung Cancer, where Daiichi Sankyo reported disappointing Phase III data for its AstraZeneca-partnered ADC datopotamab deruxtecan (Dato-DXd). In the late-stage TROPION-Lung01 study, Dato-DXd cut the risk of death by 6%, which fell short of statistical significance. Dato-DXd’s overall survival benefit in the study’s non-squamous population was likewise not statistically significant.
Daiichi Sankyo and AstraZeneca are seeking approval for Dato-DXd in non-squamous NSCLC, with a target action date of Dec. 20, 2024.
