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

NCT07720258 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NCCH2503/MK018
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

Brief 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

Keywords

Sacituzumab Tirumotecan; Small Bowel Adenocarcinoma; Advanced

Outcome Measures

Primary Outcomes (1)

• Objective response rate by central review

  The objective response rate is defined as the proportion of patients in the full analysis set whose best overall response is a complete response (CR) or partial response (PR). Best overall response is defined as the best response recorded among CR, PR, stable disease (SD), progressive disease (PD), and not evaluable (NE) using RECIST version 1.1.

  Baseline up to 3 years. Overall Response is assessed every 8 weeks until 24 weeks after initiation of protocol treatment, and every 12 weeks after 25 weeks and after termination. It continues until PD confirmation or post-study treatment initiation.

Secondary Outcomes (9)

• Objective response rate by institutional review

  Baseline up to 3 years. Overall Response is assessed every 8 weeks until 24 weeks after initiation of protocol treatment, and every 12 weeks after 25 weeks and after termination. It continues until PD confirmation or post-study treatment initiation.

• Progression-free survival

  From baseline up to 3 years

• Overall survival

  From baseline up to 3 years

• Disease control rate

  From baseline up to 3 years

• Incidence of adverse events

  From baseline up to 3 years

Other Outcomes (1)

• Objective response rate according to TROP2 expression status

  Baseline up to 3 years. Overall Response is assessed every 8 weeks until 24 weeks after initiation of protocol treatment, and every 12 weeks after 25 weeks and after termination. It continues until PD confirmation or post-study treatment initiation.

Study Arms (1)

Sacituzumab tirumotecan

EXPERIMENTAL

Drug: Sacituzumab tirumotecan

Interventions

Sacituzumab tirumotecan DRUG

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.

Sacituzumab tirumotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a histologically or cytologically confirmed diagnosis of Small bowel Adenocarcinoma.
• If diagnosed before enrollment, the timing of diagnosis shall not be considered. If this histological diagnosis was performed at the referring institution (i.e., a center not participating in the study), it must be reviewed and verified by a pathologist at the participating study site.
• Corresponds to any of the following a) to c)
• It has been determined that R0 resection is not possible due to the combined resection of the invasive lesion in locally advanced small bowel adenocarcinoma.
• Diagnosed as small bowel adenocarcinoma with distant metastasis, classified as UICC-TNM stage IV.
• Diagnosed as a postoperative recurrence of small bowel adenocarcinoma.
• No Active central nervous system (CNS) metastases-including brain metastases, carcinomatous (leptomeningeal) meningitis, or symptomatic spinal metastases that require radiotherapy or surgical intervention.
• No clinically significant pericardial effusion, pleural effusion, or ascites requiring invasive interventions such as drainage is observed.
• Age ≥18 years at the time of enrollment.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• At least one target lesion by RECIST version 1.1 identified on contrast-enhanced CT (brain, neck, chest, abdomen, pelvis with ≤5 mm slice thickness) performed within 14 days prior to enrollment (same day of the week within 14 days is acceptable; this applies similarly to other time-based criteria below).
• Has been previously treated with platinum combinations (FOLFOX or CapeOX therapy) for locally advanced or metastatic small bowel adenocarcinoma and discontinued due to disease progression, recurrence, or toxicities.
• If a genomic alteration that has a tumor-agnostic indication for solid tumors has been identified, the patient must also be refractory to, intolerant of, or ineligible for the corresponding drug (e.g., pembrolizumab for MSI-High or dMMR, or the combination of dabrafenib and trametinib for BRAF V600E mutations).
• Archival tumor tissue from either the primary lesion or metastatic lesion is available at the date of enrollment. If archival tumor tissue is not available, consent has been obtained to undergo an additional biopsy to obtain tumor tissue prior to commencement of study drug administration. Assessment of TROP2 expression is mandatory for this study.
• No prior treatment with Trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugates or antibody-drug conjugates containing anti-topoisomerase I agents.

You may not qualify if:

• Has a known additional malignancy that is progressing or has required active treatment. However, the following i) to iv) are not excluded.
• i) Completely resected the following cancers: basal cell carcinoma; stage I squamous cell carcinoma; carcinoma in situ; intramucosal carcinoma; non-muscle-invasive bladder cancer.
• ii) Gastrointestinal cancers curatively resected by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR).
• ⅲ) Localized prostate cancer treated with curative intent and showing no evidence of progression, or low-risk or very low-risk localized prostate cancer (by standard guidelines) either treated with definitive intent or untreated in active surveillance with stable disease.
• iv) Other cancers with no recurrence observed within past three years.
• Patients with active gastrointestinal ulcers.
• Has a history of pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease ,or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening.
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
• Has a current and past history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to≥480 ms, prior treatment history with cardiotoxic agents and/or other serious cardiovascular and cerebrovascular diseases within 6 months before enrollment.
• Severe hypersensitivity (Grades ≥3) to study intervention, any of their excipients, and/or to another biologic therapy.
• Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks.
• Note: A list of strong inducers/inhibitors of CYP3A4 can be found at the following website:https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems
• Is currently participating in another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• National Cancer Center, Japan: lead

Study Sites (5)

Kyushu University Hospital

Fukuoka, Japan

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Japan

Location

Osaka Medical and Pharmaceutical University Hospital

Takatsuki, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

Central Study Contacts

Hirokazu Shoji, M.D., Ph.D.

CONTACT

+81.3.3542.2511; hshouji@ncc.go.jp

Hiroyuki Fujii, M.D., Ph.D.

CONTACT

+81.3.3542.2511; hifuj2@ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5)