TQB2102 with immune therapy, with or without chemotherapy, for HER2‑positive advanced gastroesophageal cancer

Phase II Clinical Trial Evaluating the Efficacy and Safety of TQB2102 for Injection in Chemotherapy With Behmosubstituted Monoclonalb/Pembrolizumab ± Chemotherapy in Patients With Unresectable, Locally Advanced, Recurrent, or Metastatic HER2-Positive Gastroesophageal Adenocarcinoma

This test will see if TQB2102, a new HER2‑targeting antibody‑drug conjugate given with benmelstobart and sometimes the PD‑1 antibody penpulimab and chemotherapy, can improve responses in people with unresectable, recurrent, or metastatic HER2‑positive gastroesophageal adenocarcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 204 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry-sponsored)
• Drugs / interventions: pembrolizumab, chemotherapy, immunotherapy, trastuzumab, Pertuzumab, Penpulimab
• Locations: 39 sites (Fuyang, Anhui and 38 other locations)
• Trial ID: NCT06767800 on ClinicalTrials.gov

What this trial studies

TQB2102 is a novel antibody‑drug conjugate that binds two nonoverlapping HER2 epitopes (ECD2 and ECD4) to increase HER2 internalization, downregulate surface HER2, and provide dual HER2 blockade. In this Phase II interventional trial, people with HER2‑positive unresectable, recurrent, or metastatic gastroesophageal adenocarcinoma will receive TQB2102 combined with benmelstobart and with or without penpulimab and chemotherapy across predefined dosing cohorts. Eligible participants must have documented HER2 overexpression (IHC 3+ or IHC 2+ with ISH positivity), at least one measurable lesion by RECIST 1.1, ECOG 0–1, and adequate organ function. The trial will track tumor response and safety to identify active and tolerable combination regimens.

Who should consider this trial

Good fit: Adults 18–75 with unresectable locally advanced, recurrent, or metastatic HER2‑positive gastroesophageal adenocarcinoma (IHC 3+ or IHC 2+/ISH+), ECOG 0–1, measurable disease, and adequate organ function are ideal candidates.

Not a fit: Patients without HER2 overexpression, with poor performance status, significant organ dysfunction, or who are heavily pretreated for metastatic disease are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could produce higher tumor response rates and longer disease control than existing HER2‑targeted approaches for this patient group.

How similar studies have performed: Other HER2‑targeted antibody‑drug conjugates (for example trastuzumab‑deruxtecan) have shown meaningful activity in HER2‑positive gastric cancer, so this dual‑epitope ADC builds on existing promising approaches.

Eligibility criteria

Inclusion Criteria:

* 18 to 75 years of age, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and life expectancy≥3 months;
* Histopathologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma;
* HER2 expression levels of Immunohistochemistry(IHC) 3+ or IHC 2+ and In Situ Hybridization (ISH) positivity were confirmed in tumor tissue;
* Subject is able to provide previous compliant PD-L1 expression level test results or is able to provide sufficient and competent tumor tissue for PD-L1 expression level testing;
* Patients who have not received prior systemic therapy for locally advanced or metastatic gastric cancer and who have experienced tumor recurrence or metastasis at least 6 months after the completion of prior adjuvant or neoadjuvant therapy may be enrolled;
* Confirmation of at least one measurable lesion according to RECIST 1.1 criteria;
* The main organs function well;
* Male or female patient had no plans to become pregnant and voluntarily take effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug.

Exclusion Criteria:

* Concurrent secondary malignancy. or other malignancy with no evidence of disease for more than 5 years;
* Uncontrollable toxic reactions above CTC AE grade 1 due to any prior therapy, excluding alopecia;
* Major surgical treatment, incisional biopsy or significant traumatic injury or prolonged unhealed wound or fracture within 28 days prior to first dose;
* Prior history of interstitial lung disease/pneumonia (non-infectious) requiring steroidal drug intervention or current concomitant (or suspected) interstitial lung disease/pneumonia;
* Arterial/venous thrombotic events, such as cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism, have occurred within 6 months prior to the first dose;
* Individuals with a history of psychiatric drug abuse who are unable to quit or have mental disorders;
* Subjects with the presence of any severe and/or uncontrolled disease；
* Subjects who have received other antitumor drugs such as chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to the first dose, or who are still within the 5 half-life of the drug (whichever occurs shortest); have received a proprietary Chinese medicine with an antitumor indication as specified in the National Medical Products Administration(NMPA) -approved drug insert within 2 weeks prior to the first dose; and have experienced any hemorrhagic or bleeding event in the month prior to the initiation of study treatment ≥CTC Patients with AE grade 3;
* Subjects with known Central nervous system (CNS) metastases and/or carcinomatous meningitis
* Presence of severe bone damage and spinal cord compression due to tumor bone metastases;
* History of live attenuated vaccination within 28 days prior to the first dose or planned live attenuated vaccination during the study;
* History of severe hypersensitivity reactions to large molecule drugs or hypersensitivity to known components of TQB2102, benmelstobart or pembrolizumab for injection;
* Active autoimmune disease requiring systemic therapy (e.g., use of disease-mitigating drugs, corticosteroids, or immunosuppressive agents) within 2 years prior to the first dose of medication
* Diagnosis of immunodeficiency or undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy that was continued within 2 weeks prior to initiation of study treatment.
* Participants who have participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first medication use
* Unstable or serious concurrent medical conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.

Where this trial is running

Fuyang, Anhui and 38 other locations

• Fuyang Cancer Hospital — Fuyang, Anhui, China (Not_yet_recruiting)
• Lu'an People's Hospital — Lu'an, Anhui, China (Not_yet_recruiting)
• Maanshan People's Hospital — Maanshan, Anhui, China (Recruiting)
• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• The first affiliated hospital of chongqing medical university — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• Gansu Prouincial Cancer Hospital — Lanzhou, Gansu, China (Not_yet_recruiting)
• Gansu Wuwei Tumour Hospital — Wuwei, Gansu, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Nanfang Hospital — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Jiangmen Central Hospital — Jiangmen, Guangdong, China (Not_yet_recruiting)
• Meizhou People's Hospital — Meizhou, Guangdong, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Guilin Medical College — Guilin, Guangxi, China (Not_yet_recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Not_yet_recruiting)
• The first affiliated hospital of hainan medical university — Haikou, Hainan, China (Not_yet_recruiting)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (Not_yet_recruiting)
• Tangshan People's Hospital — Tangshan, Hebei, China (Not_yet_recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Anyang Cancer Hospital — Anyang, Henan, China (Not_yet_recruiting)
• The 1st Affiliated Hospital of He'nan University of Science and Technology — Luoyang, Henan, China (Not_yet_recruiting)
• Puyang Oilfield General Hospital — Puyang, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Xiangyang Central Hospital — Xiangyang, Hubei, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• The Second Xiangya Hospital Of Central South University — Changsha, Hunan, China (Not_yet_recruiting)
• NanJing Drum Tower Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• Jiangning Hospital of Nanjing City — Nanjing, Jiangsu, China (Not_yet_recruiting)
• Northern Jiangsu People's Hospital — Yangzhou, Jiangsu, China (Not_yet_recruiting)
• Jilin Cancer Hospital — Changchun, Jilin, China (Not_yet_recruiting)
• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (Not_yet_recruiting)
• Fudan university shanghai cancer center — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Shanxi Cancer hospital — Taiyuan, Shanxi, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xi'an Jiao Tong University — Xi’an, Shanxi, China (Not_yet_recruiting)
• Nanchong Central Hospital — Nanchong, Sichuan, China (Not_yet_recruiting)
• Tianjin Medical University Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• Xinjiang Medical University Affiliated Cancer Hospital — Ürümqi, Xinjiang, China (Not_yet_recruiting)
• Wenzhou Medical University Affiliated First Hospital — Wenzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Ruihua Xu, Doctor

Conditions Gastroesophageal Adenocarcinoma