Phase II Trial of Iparomlimab/Tuvonralimab (QL1706) + XELOX in HER2-Negative, Low PD-L1 G/GEJ Adenocarcinoma

Official title

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

Overview

This is single - arm study to explore the safety and efficacy of iparomlimab and tuvonralimab (QL1706) combined with chemotherapy for treating her2-negative, low PD-L1 expressing, unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma

Interventions

• Drug Iparomlimab and Tuvonralimab (QL1706)
  5 mg/kg, ivdrip, Day 1, Q3W, until progressive disease or intolerable toxicity.
• Drug Oxallplation
  130 mg/m2, ivdrip, Day 1, Q3W, for the first 6 cycles.
• Drug Capectitabine Tablets
  1000 mg/m2, po, bid, Days 1-14, Q3W, until progressive disease or intolerable toxicity.

Primary outcome measures

• progression-free survival (PFS) [Time frame: 12 months after the last subject participating in]

Secondary outcome measures (5)

• overall survival (OS) [Time frame: 12 months after the last subject participating in]
• objective response rate (ORR) [Time frame: 6 months after the last subject participating in]
• duration of response (DOR) [Time frame: 12 months after the last subject participating in]
• disease control rate (DCR) [Time frame: 12 months after the last subject participating in]
• Safety (adverse event) [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Aged 18-75 years, gender is not limited;
• Pathologically confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma that is inoperable or has distant metastasis;
• HER2-negative by immunohistochemistry (IHC);
• low PD-L1 expression status (CPS < 5);
• Has at least 1 measurable lesion as determined by RECIST 1.1;
• 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;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Adequate organ function;
• The life expectancy is at least 3 months;
• Willing to join the study and signed an informed consent form (ICF) with good compliance and cooperation in follow-up.

Exclusion criteria

• Allergic to any trial drug and its excipients, or serious allergy history, or contraindication of the trial drug;
• Cardiovascular and cerebrovascular events that are not well controlled;
• 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;
• 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.);
• 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;
• 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;
• Brain metastasis or leptomeningeal metastasis;
• 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;
• 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);
• Any major surgery was performed ≤ 28 days before the first trial drug administration;
• History of allogeneic stem cell transplantation or organ transplantation;
• 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;
• Live vaccine was inoculated within 4 weeks (inclusive) before the first administration of the trial drug, not including seasonal influenza vaccines but intranasal vaccine.
• 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;
• Participating in other therapeutic clinical studies or using research instruments within 4 weeks before the first administration;
• Others conditions do not meet the inclusion according to the judgment of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 29 centers

• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• Binzhou Medical University Hospital — Binzhou
• Dezhou People's Hospital — Dezhou
• Shengli Oilfield Central Hospital — Dongying
• Qilu Hospital of Shandong University — Jinan
• Shandong Provincial Hospital Affiliated to Shandong First Medical University — Jinan
• Shandong Provincial Third Hospital — Jinan
• Jinan Central Hospital — Jinan
• … and 21 more centers

Identifiers

NCT: NCT06932068 · SEARCH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗