Sac-TMT Combined With Fruquintinib as Second-Line Treatment in Patients With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma (SKB264-Fru-GA)

Multicenter, Phase II Clinical Study of Sacituzumab Tirumotecan (Sac-TMT) in Combination With Fruquintinib as Second-Line Therapy for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction (GEJ) Adenocarcinoma; Gastro-esophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Sacituzumab Tirumotecan + Fruquintinib

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Deng, MD; Phone Number: 15802243063; Email: xymcdengting@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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:

  1. Hematology: Absolute neutrophil count (NEUT#) ≥ 1.5×10⁹/L; platelets (PLT) ≥ 80×10⁹/L; hemoglobin ≥ 90 g/L;
  2. 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;
  3. Renal function: Creatinine clearance ≥ 50 mL/min (calculated using the standard Cockcroft-Gault formula);
  4. 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.

Exclusion Criteria:

• 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:

  1. 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;
  2. Prior history of myocarditis or cardiomyopathy;
  3. 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;
• Participants who have undergone major surgery (as defined by the Investigator) within 30 days prior to the first study dose, or are still in the postoperative recovery phase from prior surgery;
• Participants with a history of severe hypersensitivity reactions to the study drug (including its excipients);
• Participants with a history of non-infectious interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid therapy; current ILD or non-infectious pneumonitis; or suspected ILD/non-infectious pneumonitis that cannot be ruled out via imaging at screening;
• Participants with a history of allogeneic tissue/organ transplantation;

• Participants previously treated with any of the following regimens (including adjuvant or neoadjuvant settings):

  1. TROP2-targeted therapy;
  2. Any therapy containing topoisomerase I inhibitors, including antibody-drug conjugates (ADCs);
  3. Systemic therapy targeting the vascular endothelial growth factor receptor (VEGFR) signaling pathway;
• Participants who received live vaccines within 30 days prior to dosing, or plan to receive live vaccines during the study period;
• Participants requiring strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 2 weeks before the first dose and throughout the study;
• Participants who received chemotherapy, radiotherapy, immunotherapy, or biotherapy within 4 weeks before the first study dose;
• Participants who received small-molecule tyrosine kinase inhibitors (TKIs), anti-tumor hormonal therapy, systemic immune stimulants (including but not limited to interferon, IL-2), or proprietary Chinese medicines with approved anti-tumor indications within 2 weeks before the first study dose;
• Participants with active infection requiring systemic anti-infective therapy within 2 weeks prior to dosing;
• Participants with any disease requiring systemic corticosteroids (>10 mg prednisone equivalent daily) or other immunosuppressants within 14 days before the first study drug administration. Nasal, inhaled, topical, intra-articular corticosteroids, and corticosteroids administered for prophylaxis of infusion reactions are permitted;
• Participants with documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disorders with a history of impaired/delayed corneal wound healing;
• Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test prior to the first dose;
• Participants with urine protein ≥2+ and 24-hour urinary protein >1 g; or with uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg);
• Any other condition that, in the Investigator's judgment, renders the subject unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sac TMT + Fruquintinib; 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; Sac TMT: 4mg/kg Q2W, IV Infusion Fruquinitinib: 3mg QD PO, d1-21, Q4W; Other Names: SKB264 + Fruquintinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigators will be presented.	Up to 2 years
Duration of Response (DOR)	For participants who demonstrate a confirmed 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 RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by investigators will be presented.	Up to 2 years
Disease Control Rate (DCR)	DCR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions), Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: less than a 30% decrease and less than a 20% increase in the sum of diameters of target lesions, with no new lesions identified) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1).	up to 2 years
Overall Survival (OS)	OS is defined as the time from the date of enrollment to the date of death from any cause. OS will be presented.	up to 3 years
Safety of combinatinal treatment	Percentage of participants who experience a treatment-related AE during the efficacy phase. An AE is any untoward medical occurrence in a clinical study participant which is considered related to the use of the study intervention.	up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploration of Efficacy predictors	Tumor tissue and plasma specimens will be collected from patients at baseline, upon disease response and at disease progression for exploratory analyses of efficacy-related biomarkers.	up to 2 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; HMPL-013
• Other Study ID Numbers: SKB264-IIT-031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No