Sacituzumab Tirumotecan (Sac-TMT/SKB264) Plus Tagitanlimab (KL-A167) in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma

NCT07701681 | Not Yet Recruiting Phase 2

• 1 other identifier: SKB264-IIT-028
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, multi-center phase II study to evaluate the efficacy and safety of sacituzumab tirumotecan (Sac-TMT/SKB264) combined with tagitanlimab (KL-A167) as 2nd line therapy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction adenocarcinoma (G/GEJA). A total of 75 participants are planned to be enrolled with 10 in the safety lead-in phase and 33 ESCC and 42 G/GEJA in expansion phase, seperately.

Conditions

ESCC; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophageal Squamous Cell Carcinoma (ESCC); GC/GEJC

Outcome Measures

Primary Outcomes (2)

• Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)

  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 reported.

  Up to 21 days

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per 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)

• Duration of Response (DOR)

  Up to ~ 2 years

• Progression-Free Survival (PFS)

  Up to ~2 years

• Disease Control Rate (DCR)

  Up to ~ 2 years

• Overall Survival (OS)

  Up to ~ 5 years

• Number of Participants Who Experience an Adverse Event (AE)

  Up to ~ 2 years

Other Outcomes (1)

• Biomarker exploratory analysis: if there is any correlation between the expression levels of TROP2, HER2, CLDN18.2 and PD-L1 with efficacy

  Up to ~2 years

Study Arms (1)

Sac-TMT + A167

EXPERIMENTAL

Drug: Sacituzumab Tirumotecan + Tagitanlimab

Interventions

Sacituzumab Tirumotecan + Tagitanlimab DRUG

Sac-TMT (SKB264): 4mg/kg, IV infusion on Day 1, Q2W A167: 900 mg via IV injection on day 1, Q2W, up to 2 years

Sac-TMT + A167

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years at the time of signing the informed consent form;
• Histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (GEJ) adenocarcinoma;
• Esophageal squamous cell carcinoma (ESCC) and gastric/gastroesophageal junction (GEJ) adenocarcinoma with disease progression following first-line anti-PD-1 combined chemotherapy, and the progression-free survival (PFS) of first-line treatment ≥3 months;
• Radical concurrent chemoradiotherapy, neoadjuvant or adjuvant therapy: disease progression occurring during treatment or within 6 months after treatment discontinuation shall be deemed failure of first-line treatment.
• (Note: This also includes patients with advanced or recurrent non-target lesions who experience re-progression after radiotherapy alone. The criteria also apply to patients receiving palliative treatment for local (non-target) lesions for more than 2 weeks.)
• Patients with HER2-positive gastric/gastroesophageal junction adenocarcinoma must have received prior anti-HER2 therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 within 7 days prior to the first administration of study treatment;
• Expected survival ≥3 months;
• At least one measurable lesion per RECIST v1.1; lesions previously irradiated shall not be selected as target lesions; subjects with only skin lesions or bone lesions are not eligible for enrollment;
• Participants must have recovered from all toxicities related to prior treatments (i.e., improved to Grade 0 or Grade 1, or met the levels specified in the eligibility criteria), except for toxicities not considered a safety risk (e.g., alopecia, vitiligo, and other asymptomatic laboratory abnormalities);
• Adequate organ function defined as follows:
• Hematology (no blood transfusion or hematopoietic stimulating agents for correction within 14 days): hemoglobin (Hb) ≥9 g/dL; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count (PLT) ≥100×10⁹/L; neutrophil count (NEUT#) ≥1.5×10⁹/L;
• Serum total bilirubin ≤1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤2.5 × ULN.
• For subjects with liver metastases: ALT and AST ≤5 × ULN, serum bilirubin ≤2 × ULN.
• For subjects with liver and/or bone metastases: ALP ≤5 × ULN; serum albumin ≥30 g/L;

You may not qualify if:

• Participants diagnosed with other malignant tumors within 3 years prior to study drug administration, except for tumors cured by local therapy (e.g., basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, cervical carcinoma in situ, etc.);
• Participants with known meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or spinal cord compression, or active central nervous system (CNS) metastases without prior local treatment. Participants with previously locally treated brain metastases may be enrolled if they remain clinically stable for at least 4 weeks prior to the first dose and do not require corticosteroids or anticonvulsants for a minimum of 14 days;
• Participants with clinically significant cardiovascular diseases, including:
• Severe or uncontrolled cardiac disorders or clinical symptoms requiring treatment within 6 months before the first study dose, including New York Heart Association (NYHA) Class III or IV congestive heart failure, drug-refractory unstable angina, severe arrhythmias requiring pharmacotherapy (excluding atrial fibrillation or paroxysmal supraventricular tachycardia), and myocardial infarction;
• Prior history of myocarditis or cardiomyopathy;
• QTc interval \>480 ms at baseline measurement;
• Participants with severe and/or uncontrolled concomitant diseases, such as decompensated cirrhosis, nephrotic syndrome, poorly controlled hypertension, symptomatic pleural/pericardial effusion or ascites requiring repeated drainage;
• Participants diagnosed with active hepatitis B \[hepatitis B surface antigen (HBsAg) positive, with HBV-DNA ≥ 500 IU/mL or above the lower limit of quantification, whichever is higher\] or hepatitis C (positive anti-HCV antibody with HCV-RNA above the lower limit of quantification);
• Participants with poorly controlled known human immunodeficiency virus (HIV) infection, including HIV-infected individuals with a history of Kaposi's sarcoma and/or multicentric Castleman's disease;
• Participants with known active tuberculosis;
• Participants with documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or a history of corneal disorders that hinder or delay corneal wound healing;
• Participants who have undergone major surgery (as defined by the investigator) within 30 days before the first study dose or are still recovering from prior surgery;
• Participants with known allergy or hypersensitivity to the study drug or its excipients, or a prior history of severe hypersensitivity reactions to monoclonal antibodies;
• Participants with a history of interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid therapy, current ILD/pneumonia, or suspected ILD/pneumonia that cannot be ruled out by imaging at screening;
• Participants with a history of allogeneic tissue or organ transplantation; Autoimmune diseases requiring systemic therapy within the past 2 years or anticipated immunosuppressive therapy during the study period. Participants with well-controlled type 1 diabetes, euthyroid thyroiditis, hypothyroidism adequately managed via hormone replacement therapy (HRT), or skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis) are eligible for enrollment;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Feng Wang, MD

CONTACT

+86 020 87343795; wangfeng@sysucc.org.cn

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: July 8, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)