Sacituzumab Tirumotecan (MK-2870) in Patients With Advanced Small Bowel Adenocarcinoma Refractory or Intolerant to Platinum-Based Combination Therapy

Summary

Small bowel adenocarcinoma is a rare cancer with a poor prognosis. For patients with locally advanced or metastatic disease, the usual first treatment is chemotherapy with platinum-based combinations such as FOLFOX or CapeOX. However, once the cancer grows after this treatment or the side effects become too severe, there is no widely accepted standard second-line therapy, and outcomes are generally poor. New treatment options are therefore urgently needed.

In a recent translational research study conducted by Fujii, Shoji, et al., immunohistochemical staining for TROP2 was performed in 51 patients with pathologically diagnosed small bowel adenocarcinoma, and TROP2 positivity was confirmed in 43 cases (84.3%). Furthermore, patient-derived organoids were established using tumor tissues obtained from patients with small bowel adenocarcinoma, and the in vitro efficacy of sacituzumab tirumotecan was evaluated. A concentration-dependent growth-inhibitory effect was observed, with significant sensitivity observed in the nanomolar concentration range. Therefore, treatment with sacituzumab tirumotecan targeting TROP2 is expected to improve the prognosis of patients with small bowel adenocarcinoma.

The METROPOLIS trial is a multicenter, single-arm, phase II investigator-initiated trial designed to evaluate the efficacy and safety of sacituzumab tirumotecan in patients with locally advanced or metastatic small bowel adenocarcinoma that has progressed during or after, or is intolerant to, platinum-based combination chemotherapy (FOLFOX or CapeOX). Eligible patients are adults (aged 18 years or older) with histologically or cytologically confirmed small bowel adenocarcinoma, a good performance status, adequate organ function, and at least one measurable lesion on a CT scan. Patients who have genomic alterations that make them candidates for previously approved "tumor-agnostic" targeted drugs (for example, high microsatellite instability or high tumor mutational burden) must already have tried and not benefited from, or not tolerated, those treatments. TROP2 positivity is not required for study participation; however, assessment of TROP2 expression is mandatory for exploratory biomarker analyses.

Sacituzumab tirumotecan at 4 mg/kg is administered intravenously on Days 1 and 15 of each 28-day cycle and continued until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met. Tumor scans with contrast-enhanced CT will be performed every 8 weeks up to week 24 and every 12 weeks thereafter to monitor the response of the sacituzumab tirumotecan. The primary objective is to determine the proportion of patients achieving a tumor response to sacituzumab tirumotecan, as assessed by independent radiologic review. Key secondary objectives include progression-free survival, overall survival, duration of response, and safety profiling.

In addition, this study includes a prespecified translational research program. Tumor samples will be examined for TROP2 using immunohistochemistry, and researchers will investigate the relationship between TROP2 and the effects of sacituzumab tirumotecan. Blood and tissue samples will also be collected before treatment, during treatment, and at the time of cancer progression, when possible, for detailed "multi-omics" analyses. These translational studies aim to elucidate why some patients respond whereas others do not, and to identify biomarkers that could inform future treatment strategies for small bowel adenocarcinoma.

The METROPOLIS trial has been approved by the Institutional Review Board of the National Cancer Center, Japan, as well as by the ethics committees at participating sites. This trial is conducted with funding and sacituzumab tirumotecan supplied by MERCK SHARP \& DOHME LLC. Enrollment began in January 2027 and is planned to continue through December 2028, with patients followed for at least 12 months after the last participant is enrolled.

Conditions

• Advanced Small Bowel Adenocarcinoma

Interventions

DRUG

Sacituzumab tirumotecan

Sacituzumab tirumotecan at 4 mg/kg is administered intravenously on Days 1 and 15 of each 28-day cycle and continued until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met.

Sponsors & Collaborators

• National Cancer Center, Japan

  lead OTHER_GOV

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-01

Primary Completion

2028-12-31

Completion

2029-12-31

Countries

• Japan

Study Locations