Merck's China-Originated ADC Sacituzumab Tirumotecan Demonstrates Promising Efficacy in Phase II Lung Cancer and Phase III Breast Cancer Trials

Jun 27, 2024 08:29 CST Updated 08:30

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Recently, MSD announced itsADC DrugsSacituzumab Tirumotecan Shows Positive Efficacy in Phase II Lung Cancer and Phase III Breast Cancer Studies.

Sacituzumab Tirumotecan (SKB-264/MK-2870) is a new generation Trop2 ADC, featuring an innovative and sophisticated structural design, excellent drug stability, and high affinity. In May 2022, MSD acquired it from Kelun Pharma's subsidiary.Kelun BotaiThe introduction of this ADC drug amounted to a transaction value of $1.41 billion.

In various cancers such as breast cancer, gastric cancer, and ovarian cancer, the overexpression of Trop-2 is associated with accelerated tumor growth and poor prognosis. Trop-2 is a type of internalizing cell membrane receptor, enabling ADC drugs targeting it to enter the cell lysosome and release more cell-permeable cytotoxic payloads, generating stronger effects.Bystander Effect。

Speaking of which, it is necessary to mention the world's first marketed TROP2 ADC - Gilead'sTrodelvy, was approved in April 2020 for second-line or later treatment of adult patients with metastatic triple-negative breast cancer, becoming the world's first ADC for the treatment of triple-negative breast cancer. In 2021, the drug received full FDA approval and has now been launched in more than 30 countries, including the United States, China, and the European Union.

In 2023, Trodelvy generated $1.063 billion in revenue, a significant year-over-year increase of 56%, ranking fourth on the global ADC drug sales list.Sacituzumab tirumotecan has the same antibody as Trodelvy, but with a different payload and linker.In the treatment of relapsed or metastaticTriple-Negative Breast Cancerin a Phase 3 trial demonstrated its impressive results.

Phase III Study of Breast Cancer

The study enrolled 263 breast cancer patients. As of the interim data on June 21, 2023, compared with chemotherapy, sacituzumab tirumotecan reduced the risk of disease progression or death (PFS) by 69%. The median PFS in the treatment group was 5.7 months, compared to 2.3 months in the chemotherapy group; the ORR in the treatment group was 43.8%, while the ORR for chemotherapy was 12.8%.

In terms of safety, the most common ≥3 grade treatment-related adverse events (TRAEs) were decreased neutrophil count (32.3%), anemia (27.7%), and decreased white blood cell count (25.4%).

Phase II Study of Lung Cancer

This Phase II study evaluated the efficacy of sacituzumab tirumotecan in combination with Kelun BioTech's self-developed PD-L1-targeting humanized monoclonal antibody KL-A167 in patients with advanced non-small cell lung cancer (NSCLC). Patients were assigned to receive 5 mg/kg sacituzumab tirumotecan every three weeks along with 1,200 mg KL-A167 Q3W (Cohort 1A) or 900 mg KL-A167 every two weeks (Cohort 1B).

As of January 2, 2024, the median follow-up duration for the 40 participants in Cohort 1A was longer at 14 months, with an ORR of 48.6% and a median PFS of 15.4 months. In Cohort 1B, the median follow-up duration for the 63 patients was only 6.9 months; the median PFS was not reached, but the six-month PFS rate was 84.6%, and the ORR was 77.6%.

One patient in the 1B group discontinued the study due to drug allergy. Common grade 3 or 4 treatment-related adverse events (TRAEs) included decreased blood cell counts, such as neutropenia, leukopenia, and anemia, as well as rash and drug eruption.

Moreover, MSD is evaluating sacituzumab tirumotecan in combination with its PD-1 therapy Keytruda as a first-line treatment for patients with metastatic NSCLC in a Phase III trial (NCT06170788). The trial is expected to enroll approximately 614 participants and conclude in 2028.

ADC has been a field of interest in recent years, with MSD strengthening its ADC portfolio through investments. In October 2023, MSD collaborated with Daiichi Sankyo to develop and commercialize the latter's three ADC candidates, in a deal worth up to $22 billion.

Yesterday, MSD brought more good news.PD-1 Inhibitor Pembrolizumab (Trade Name: Keytruda)Approved by the National Medical Products Administration (NMPA) of China in combination with trastuzumab, fluoropyrimidine-based and platinum-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) as assessed by a validated test. The approval of this new indication is based on data from a global Phase III clinical trial.

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