Sac-TMT Combined With Fruquintinib as Second-Line Treatment in Patients With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

NCT07689292 | Not Yet Recruiting Phase 2

• 1 other identifier: SKB264-IIT-031
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase 2 multicenter study that will evaluate the safety and efficacy of sacituzumab tirumotecan (Sac-TMT) plus fruquintinib for the treatment of participants with locally advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma who have failed 1 prior line of therapy.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction (GEJ) Adenocarcinoma; Gastro-esophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase

  DLTs are defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The percentage of participants who experience at least one DLT will be presented.

  Up to ~21 days

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by investigators will be presented.

  Up to 2 years

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

• Disease Control Rate (DCR)

  up to 2 years

• Overall Survival (OS)

  up to 3 years

• Safety of combinatinal treatment

  up to 2 years

Other Outcomes (1)

• Exploration of Efficacy predictors

  up to 2 years

Study Arms (1)

Sac TMT + Fruquintinib

EXPERIMENTAL

Following a 21 day run-in with sacituzumab tirumotecan at 4 mg/kg IV infusion on day 1 of a 2-week cycle plus fruquintinib at 3 mg QD PO on days 1-21 of a 4-week cycle, participants receive sacituzumab tirumotecan at 4 mg/kg IV infusion on day 1 of a 2-week cycle plus fruquintinib at 3 mg QD PO on days 1-21 of a 4-week cycle until discontinuation.

Drug: Sacituzumab Tirumotecan + Fruquintinib

Interventions

Sacituzumab Tirumotecan + Fruquintinib DRUG

Sac TMT: 4mg/kg Q2W, IV Infusion Fruquinitinib: 3mg QD PO, d1-21, Q4W

Also known as: SKB264 + Fruquintinib

Sac TMT + Fruquintinib

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed metastatic or locally advanced adenocarcinoma of the gastric or gastroesophageal junction, unresectable;
• Subjects who have failed first-line standard systemic therapy, or experienced disease progression or recurrence within 6 months after completion of adjuvant systemic therapy (HER2-positive subjects must have received prior anti-HER2 therapy);
• Have at least one measurable lesion per RECIST v1.1, subjects with only cutaneous or bone lesions are not eligible for enrollment;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 within 7 days prior to study drug administration;
• Estimated life expectancy \> 12 weeks.
• Adequate organ and bone marrow function (no transfusions, recombinant human thrombopoietin or colony-stimulating factor administered within 2 weeks prior to dosing), defined as follows:
• Hematology: Absolute neutrophil count (NEUT#) ≥ 1.5×10⁹/L; platelets (PLT) ≥ 80×10⁹/L; hemoglobin ≥ 90 g/L;
• Hepatic function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); for subjects with baseline liver metastases, ALT and AST ≤ 5 × ULN; albumin ≥ 30 g/L; total bilirubin (TBIL) ≤ 1.5 × ULN;
• Renal function: Creatinine clearance ≥ 50 mL/min (calculated using the standard Cockcroft-Gault formula);
• Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤ 1.5 × ULN.
• All acute toxicities from prior treatments have recovered to Grade 1 or lower (alopecia and vitiligo are excluded). Note: Subjects with any grade of prior endocrine adverse events may be enrolled if they only require maintenance hormone replacement therapy and are stable and asymptomatic at screening.
• Females of childbearing potential and males with partners of childbearing potential must agree to use effective medical contraception from the time of informed consent signature through 6 months after the last dose of study drug;
• The subject voluntarily participates in this study, signs the informed consent form, and is able to comply with protocol-specified study visits and related procedures.

You may not qualify if:

• Participants unable to receive oral administration due to dysphagia, intractable vomiting, or known drug malabsorption;
• Participants with active gastric/duodenal ulcer, ulcerative colitis, intestinal obstruction, or other gastrointestinal disorders/conditions judged by the Investigator to carry a risk of gastrointestinal hemorrhage or perforation; or with a history of intestinal perforation or fistula within the preceding 6 months; or with unresolved intestinal perforation/fistula following prior surgical repair;
• Participants with known meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or spinal cord compression, or active/untreated central nervous system (CNS) metastases. Participants with previously locally treated brain metastases may be enrolled if clinically stable for at least 4 weeks prior to dosing and not requiring corticosteroids or anticonvulsants for a minimum of 14 days before the first dose;
• Participants diagnosed with another malignant tumor within 3 years prior to dosing, except malignancies cured by local therapy such as basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, carcinoma in situ of the cervix, etc.;
• Participants with clinically significant cardiovascular disease, defined as:
• Severe or uncontrolled cardiac disease or symptomatic cardiac conditions requiring treatment within 6 months prior to the first study dose, including congestive heart failure classified as New York Heart Association (NYHA) Class III or IV, medically refractory unstable angina, severe arrhythmias requiring pharmacotherapy (excluding atrial fibrillation or paroxysmal supraventricular tachycardia), and myocardial infarction;
• Prior history of myocarditis or cardiomyopathy;
• Baseline corrected QT (QTc) interval \> 480 ms;
• Participants with a history of arterial thromboembolism or deep vein thrombosis within the preceding 6 months;
• Participants with documented or historical significant bleeding within 2 months prior to dosing, including melena, hematemesis, hemoptysis, ≥++ fecal occult blood. Subjects with 1+ fecal occult blood and underlying primary gastrointestinal lesions must complete gastroscopy prior to enrollment to rule out active bleeding or ulcers;
• Participants with a history of stroke and/or transient ischemic attack (TIA) within 12 months prior to dosing;
• Participants with severe and/or uncontrolled systemic diseases, such as unregulated metabolic disorders, active inflammatory bowel disease, or gastrointestinal perforation;
• Participants with active hepatitis B \[hepatitis B surface antigen (HBsAg)-positive, with HBV-DNA ≥1000 IU/mL or above the lower limit of quantification (LLOQ), whichever is higher\] or hepatitis C (hepatitis C antibody-positive with HCV-RNA above the LLOQ). Note: HBsAg-positive subjects must receive anti-HBV antiviral therapy throughout study treatment;
• Participants with known poorly controlled human immunodeficiency virus (HIV) infection; subjects with active syphilis infection;
• Participants with known active pulmonary tuberculosis;

Sponsors & Collaborators

• Peking Union Medical College Hospital: collaborator
• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Adenocarcinoma

Interventions

HMPL-013

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Ting Deng, MD

CONTACT

15802243063; xymcdengting@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 8, 2026
• Study Start: July 31, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share