Combining iparomlimab and tuvonralimab with chemotherapy for advanced gastric cancer

Safety and Efficacy of Iparomlimab and Tuvonralimab (QL1706) Combined With Chemotherapy for the Treatment of HER2-Negative, Low PD-L1 Expressing, Unresectable or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Single-Arm Trial

This study is testing a new combination of two drugs with chemotherapy to see if it can help people with advanced gastric cancer feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 77 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Qilu Hospital of Shandong University (Academic / other)
• Drugs / interventions: chemotherapy, iparomlimab, tuvonralimab
• Locations: 29 sites (Zhengzhou, Henan and 28 other locations)
• Trial ID: NCT06932068 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of a combination treatment involving iparomlimab and tuvonralimab (QL1706) alongside XELOX chemotherapy for patients with HER2-negative, low PD-L1 expressing, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. It is a single-arm Phase II trial that aims to determine how well this treatment works in this specific patient population. Participants will be monitored for their response to the treatment and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma and low PD-L1 expression.

Not a fit: Patients with HER2-positive tumors or those who have received systemic treatment within the past six months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced gastric cancer who currently have limited treatment choices.

How similar studies have performed: While this approach is novel in this specific context, similar combination therapies have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

1. Aged 18-75 years, gender is not limited;
2. Pathologically confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma that is inoperable or has distant metastasis;
3. HER2-negative by immunohistochemistry (IHC);
4. low PD-L1 expression status (CPS \< 5);
5. Has at least 1 measurable lesion as determined by RECIST 1.1;
6. No systematic treatment in the past, or the patient has received neoadjuvant/adjuvant chemotherapy, but the disease progresses or relapses more than 6 months after the end of treatment;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
8. Adequate organ function;
9. The life expectancy is at least 3 months;
10. Willing to join the study and signed an informed consent form (ICF) with good compliance and cooperation in follow-up.

Exclusion Criteria:

1. Allergic to any trial drug and its excipients, or serious allergy history, or contraindication of the trial drug;
2. Cardiovascular and cerebrovascular events that are not well controlled;
3. Has received systematic treatment with Chinese patent medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use for ascites control) before the first administration within 2 weeks;
4. Have a history of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, acute lung disease, or systemic disease with poor control (including but not limited to diabetes, hypertension, etc.);
5. Have a history of active immune deficiency or autoimmune diseases, including HIV positive test, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or autoimmune diseases;
6. Severe chronic or active infection requires systemic antibacterial, antifungal or antiviral treatment, including tuberculosis infection.Have a history of active tuberculosis infection ≥ 1 year before recruitment should also be excluded, unless proved has been completed appropriate treatment;
7. Brain metastasis or leptomeningeal metastasis;
8. Clinically significant pleural effusion, pericardial effusion or ascites should be drained for many times within 2 weeks before the first administration of the trial drug;
9. Has a second clinically detectable primary malignant tumor at the time of recruitment, or there were other malignant tumors in the past 5 years (except for fully treated skin basal cell carcinoma or cervical carcinoma in situ);
10. Any major surgery was performed ≤ 28 days before the first trial drug administration;
11. History of allogeneic stem cell transplantation or organ transplantation;
12. Duodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases at present; or other conditions that may cause gastrointestinal bleeding or perforation judged by the researchers; or history of intestinal perforation or fistula, but has not recovered after surgical treatment;
13. Live vaccine was inoculated within 4 weeks (inclusive) before the first administration of the trial drug, not including seasonal influenza vaccines but intranasal vaccine.
14. Has other factors that may lead to the forced termination of this trial according to the judgment of the investigator, such as other serious diseases (including psychological and mental diseases) requiring combined treatment, serious laboratory examination abnormalities, and family or social factors, which may affect the safety of the subject, or the collection of data and samples;
15. Participating in other therapeutic clinical studies or using research instruments within 4 weeks before the first administration;
16. Others conditions do not meet the inclusion according to the judgment of the investigator.

Where this trial is running

Zhengzhou, Henan and 28 other locations

• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• Binzhou Medical University Hospital — Binzhou, Shandong, China (Recruiting)
• Dezhou People's Hospital — Dezhou, Shandong, China (Recruiting)
• Shengli Oilfield Central Hospital — Dongying, Shandong, China (Recruiting)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (Recruiting)
• Shandong Provincial Hospital Affiliated to Shandong First Medical University — Jinan, Shandong, China (Recruiting)
• Shandong Provincial Third Hospital — Jinan, Shandong, China (Recruiting)
• Jinan Central Hospital — Jinan, Shandong, China (Recruiting)
• Jinan Third People's Hospital — Jinan, Shandong, China (Recruiting)
• Shandong Qianfoshan Hospital — Jinan, Shandong, China (Recruiting)
• Affiliated Hospital of Jining Medical College — Jining, Shandong, China (Recruiting)
• Liaocheng People's Hospital — Liaocheng, Shandong, China (Recruiting)
• Linyi Cancer Hospital — Linyi, Shandong, China (Recruiting)
• Linyi People's Hospital — Linyi, Shandong, China (Recruiting)
• Qilu Hospital of Shandong University(Qingdao) — Qingdao, Shandong, China (Recruiting)
• Qingdao Municipal Hospital — Qingdao, Shandong, China (Recruiting)
• Qingdao Municipal Hospital — Qingdao, Shandong, China (Recruiting)
• The Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (Recruiting)
• Taian City Central Hospital — Tai’an, Shandong, China (Recruiting)
• The Second Affiliated Hospital of Shandong First Medical University — Tai’an, Shandong, China (Recruiting)
• Tengzhou Central People's Hospital — Tengzhou, Shandong, China (Recruiting)
• Weifang Hospital of Traditional Chinese Medicine — Weifang, Shandong, China (Recruiting)
• Weihai Central Hospital — Weihai, Shandong, China (Recruiting)
• Yantai Yuhuangding Hospital — Yantai, Shandong, China (Recruiting)
• Yantai Yuhuangding Hospital — Yantai, Shandong, China (Recruiting)
• Yantaishan Hospital — Yantai, Shandong, China (Recruiting)
• Zibo Central Hospital — Zibo, Shandong, China (Recruiting)
• Zibo First People's Hospital — Zibo, Shandong, China (Recruiting)
• Jining First People's Hospital — Jining, China (Recruiting)

Study contacts

• Principal investigator: Lian Liu, MD, PHD — Qilu Hospital of Shandong University
• Study coordinator: Lian Liu, MD, PHD

Conditions HER2 Negative; Low PD-L1 Expressing; Unresectable or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma