Merck Reports Key Clinical Data from Three Investigational New Drug Candidates at ASCO 2025

The 2025 ASCO Annual Meeting is currently underway. MSD presented multiple research data on its portfolio and pipeline at the conference, covering more than 25 different types of cancer. Among these, MSD delivered an oral presentation for the first time to announcePipeline in Development: MK-1084 Colorectal Cancer、Zilovertamab Vedotin Diffuse Large B-Cell LymphomaClinical data, and the first disclosure of Patritumab deruxtecanOS Data from the Key Phase III Study of Lung Cancer.

Zilovertamab vedotin：ROR1 ADC

Indications: Diffuse Large B-Cell Lymphoma (DLBCL)

Abstract Number: 7005

Zilovertamab vedotin is an ADC targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1),Currently in Phase III clinical trials, ranking first in the ROR1 ADC field.。

At this year's conference, MSD announced the Phase II/III trial WaveLINE-003 for the first time in an oral presentation.(NCT05139017) Data from the study, which aimed to evaluate Zilovertamab vedotin(hereinafter referred to as "ZV")Combined Standard Treatment(Rituximab + Gemcitabine-Oxaliplatin [R-GemOx])Efficacy in patients with relapsed or refractory DLBCL.

Screenshot source: ASCO official website

The primary endpoint of the WaveLINE-003 study is safety and determination of the recommended Phase 2 dose. (RP2D). The secondary endpoint is the objective response rate. (ORR) And Duration of Relief (DOR), as well as overall survival. This presentation showcases the results from the dose-confirmation phase of the trial. As of August 1, 2024, Cohort A enrolled a total of 40 patients. The median number of prior treatment lines was 2, with a median follow-up time of 9.8 months.

The study reported 7 cases of dose-limiting toxicity.（DLT）Among them, 1 case in the ZV 1.5 mg/kg group, 2 cases in the ZV 1.75 mg/kg group, and 4 cases in the ZV 2.0 mg/kg group. Treatment-related adverse events were reported by 39 patients (98%).(AE)，Twenty-six patients reported ≥ Grade 3 treatment-related adverse events (AEs). Two patients discontinued the treatment due to AEs, and one patient died from sepsis (treatment-related). All cases occurred in the 2.0 mg/kg dose group.RP2D determined as 1.75 mg/kg。

Efficacy data for the 1.5 mg/kg group, 1.75 mg/kg group, and 2.0 mg/kg group show:ORR were 27%, 56%, and 57%, respectively.; The median DOR was 14.4 months, 8.7 months, and not reached, respectively.（NR）; The median OS was 11.5 months, NR, and 7.4 months, respectively, with 6-month OS rates of 70.0%, 78.8%, and 68.6%.

In summary, Zilovertamab vedotin at a dose of 1.75 mg/kg(RP2D Dose)The study has shown good efficacy and acceptable safety, and has now entered Phase III clinical trials.

Patritumab deruxtecan：HER3 ADC

Indications: EGFR Mutation-positive Advanced NSCLC

Abstract Number: 8506

Patritumab deruxtecan（HER3-DXd）It is a HER3-targeted ADC, co-developed and commercialized by Daiichi Sankyo and MSD.(Excluding Japan)At this year's conference, researchers announced HER3-DXd in an oral presentation format.EGFR-Mutant Advanced NSCLC Resistant to Third-Generation EGFR TKI TreatmentResults of the Phase III HERTHENA-Lung02 Study.

Screenshot source: ASCO official website

HERTHENA-Lung02（NCT05338970）The primary endpoint of the study was progression-free survival assessed by BICR.（PFS）. The key secondary endpoint was overall survival（OS）. A total of 586 patients were enrolled in the study. As of May 31, 2024, the data cutoff date for the primary PFS analysis, the median study follow-up time was 10.7 months, with the HER3-DXd group and investigator-selected platinum-based chemotherapy.（PBC）The median treatment durations for the groups were 5.5 months and 4.6 months, respectively.

Efficacy data show:PFS in the HER3-DXd group was significantly better than in the PBC group.（HR，0.77）The median PFS for the HER3-DXd group and the PBC group were 5.8 months vs. 5.4 months, respectively. The PFS rates at 6 months were 50% vs. 38%, at 9 months were 29% vs. 19%, and at 12 months were 18% vs. 5%. The ORR for the HER3-DXd group and the PBC group were 35.2% vs. 25.3%, respectively, and the median DOR were 5.7 months vs. 5.4 months.

The abstract data from ASCO shows that, as of the interim data cutoff date specified in this protocol, the OS data is not yet mature. However, on May 29, Daiichi Sankyo and MSD jointly issued a press release stating,OS Results for HER3-DXd in HERTHENA-Lung02 Phase III Clinical Trial Did Not Reach Statistical Significance，Both parties have also withdrawn the HER3-DXd submission to the FDA for NSCLC.。

MK-1084: KRAS G12C Inhibitor

Indications: Colorectal Cancer

Abstract Number: 3508

MK-1084 is a next-generation selective KRAS G12C-GDP covalent inhibitor. Phase I clinical trial KANDLELIT-001 (NCT05067283) Aiming to evaluate MK-1084 in patients who have previously received treatmentKRAS G12C-Mutant Solid Tumors(Including non-small cell lung cancer and colorectal cancer)Safety and preliminary antitumor activity in patients. The primary endpoints were DLT, adverse events, and adverse events leading to discontinuation. Secondary endpoints included ORR assessed by investigators according to RECIST v1.1.

This conference disclosed for the first time MK-1084 monotherapy, MK-1084 + Cetuximab, and MK-1084 + Cetuximab + mFOLFOX6 treatments.Advanced KRAS G12C-Mutant Colorectal CancerPatient data. In the 1+3 group of this study, 99 patients(Including 53 CRC patients)Received MK-1084 monotherapy; in Group 5, 34 patients(Including 23 patients who had previously received ≥2 lines of treatment)Received MK-1084 + cetuximab treatment; in Group 6, 20 patients(including 10 patients who have not received prior treatment)Received treatment with MK-1084 + Cetuximab + mFOLFOX6 regimen.

The median follow-up times for groups 1+3, 5, and 6 were 14.8 months, 5.3 months, and 1.9 months, respectively. Efficacy data showed that 1+3 Group（n=53）The ORR for CRC patients was 36%, Group 5（n=34）The ORR was 50%, Group 6（n=14）The ORR was 14%.. All remissions were partial remissions.

Safety data showed that one patient in Group 6 experienced DLT; no DLT was observed in Groups 1, 3, and 5. The incidence of treatment-related adverse reactions in Groups 1+3, 5, and 6 were 62%, 97%, and 90%, respectively, with ≥Grade 3 adverse reaction rates of 9%, 18%, and 25%, respectively. The proportions of patients discontinuing treatment due to adverse reactions were 1%, 3%, and 15%, respectively. No treatment-related deaths occurred.

In summary, preliminary data indicate that MK-1084 monotherapy, MK-1084 plus cetuximab, and MK-1084 plus cetuximab and mFOLFOX6 have manageable safety profiles and demonstrate antitumor activity in patients with advanced colorectal cancer harboring KRAS G12C mutations. Patient follow-up and enrollment in the study are ongoing.

For more information on MSD's research data disclosed at this year's ASCO, please press and hold the QR code below to visit.Insight Database "Clinical Trial Results Module"To view.

Cover Source:Insight Database Chart

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