ASCO 2024: MSD’s ADC effective in lung and breast tumors

Merck & Co (MSD) has recently shared promising outcomes from studies of its antibody-drug conjugate (ADC) therapy, sacituzumab tirumotecan. This therapy targets the trophoblast cell-surface antigen 2 (TROP2) and is linked to a belotecan-derivative topoisomerase I inhibitor payload. Distinct from Gilead Sciences’ Trodelvy (sacituzumab govitecan), sacituzumab tirumotecan employs a different payload and linker. MSD acquired this ADC therapy and six other candidates from Sichuan Kelun-Biotech in 2022.

Data from an open-label Phase II trial (NCT05351788) and a Phase III study (NCT05347134) will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from May 31 to June 4. The Phase II trial assessed sacituzumab tirumotecan combined with Kelun’s PD-L1 targeting monoclonal antibody, KL-A167, in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). The 40 patients in cohort 1A, who had a longer median follow-up of 14 months, demonstrated an objective response rate (ORR) of 48.6% and a median progression-free survival (PFS) of 15.4 months. The 63 patients in cohort 1B, with a median follow-up of 6.9 months, did not reach median PFS but had a six-month PFS rate of 84.6% and an ORR of 77.6%.

In the Phase III study, sacituzumab tirumotecan was compared with chemotherapy in 263 patients with locally recurrent or metastatic triple-negative breast cancer. The study achieved the primary endpoint of PFS, showing a 69% reduction in the risk of progression or death, based on an interim analysis as of June 21, 2023. According to blinded independent central reviews (BICRs), the median PFS for sacituzumab tirumotecan was 5.7 months compared to 2.3 months for chemotherapy. The ORR for sacituzumab tirumotecan was 43.8%, whereas chemotherapy had an ORR of 12.8%.

As of the data cut-off on November 30, 2023, with a median follow-up of 10.4 months, median overall survival (OS) had not been reached for the sacituzumab tirumotecan group, while the chemotherapy group had a median OS of 9.4 months. Commonly observed Grade 3 or 4 treatment-related adverse events (TRAEs) in both trials included decreased blood counts such as neutropenia, leukopenia, and anemia, along with rash and drug eruption.

Additionally, MSD is evaluating sacituzumab tirumotecan in combination with its PD1 therapy Keytruda (pembrolizumab) as a first-line treatment for patients with metastatic NSCLC in a Phase III trial (NCT06170788). This trial aims to enroll approximately 614 participants and is expected to conclude in 2028.

The ASCO meeting will feature data from multiple companies on their ADC therapies, highlighting the increasing interest in this area. Notably, MSD has been making significant investments to enhance its ADC portfolio. In October 2023, the company partnered with Daiichi Sankyo to develop and commercialize three of its DXd ADC candidates, possibly investing up to $22 billion in the collaboration.