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Utidelone Capsule Combined with Capecitabine and Oxaliplatin in First-line Treatment of PD-L1-negative Gastric or Gastroesophageal Junction Adenocarcinoma Patients

B

Beijing Biostar Pharmaceuticals

Status and phase

Not yet enrolling
Phase 3
Phase 2

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Treatments

Drug: Utidelone Capsule
Drug: Capecitabine
Drug: Oxaliplatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT06841679
BG02-2404

Details and patient eligibility

About

This is a multi-national, open-label, randomized, seamless phase II/III clinical study of UTD2 combined with capecitabine and oxaliplatin to evaluate the efficacy and safety in patients with PD-L1-negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma untreated with systemic treatment in advanced setting.

Enrollment

778 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Participants must meet the following criteria to be eligible for the study:

    1. Sign the informed consent form (ICF) to participate and follow the study procedures.

    2. Male and female aged ≥ 18 years.

    3. Participant must have unresectable, advanced or metastatic GC or GEJ and have histologically/pathologic confirmed predominant adenocarcinoma. The documentation of GEJ involvement can include biopsy, endoscopy, or imaging.

    4. Participant must have tumor with PD-L1 CPS < 1 by immunohistochemical (IHC). IHC results from site are acceptable.

    5. Participant must have at least one measurable lesion per RECIST 1.1 criteria.

    6. Participant must not receive previously systemic treatment in the advanced setting. Previously neoadjuvant/adjuvant therapy for GC or GEJ with no progression after 6 months from completion is allowed. Palliative radiotherapy is allowed.

    7. Eastern Cooperative Oncology Group (ECOG) status of 0 to 1.

    8. Participant with adequate haematological function (CTCAE v5.0 Grade ≤ 1) within 1 week before enrollment (based on routine laboratory values at each site) and who have not received recombinant human granulocyte colony-stimulating factor (rhG-CSF) or blood products/erythropoietin (EPO) within 14 days before enrollment.

      • White blood cell count (WBC) ≥ 3.0 × 109/L;
      • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
      • Platelet count (PLT) ≥ 100 × 109/L;
      • Hemoglobin (Hb) ≥ 9.0 g/dL.
    9. Participant with adequate liver and renal function (CTCAE v5.0 Grade ≤ 1) within 1 week before enrollment (based on routine laboratory values at each site).

      • Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN);
      • Alanine aminotransferase (ALT) ≤ 3 × ULN (≤ 5 × ULN in patients with hepatic metastases);
      • Aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN in patients with hepatic metastases);
      • Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
      • Creatinine clearance (Ccr) ≥ 60 mL/min.
    10. Female Participants of childbearing potential must agree to use highly effective contraceptive methods during the study and within 6 months after the last dose of the investigational product. Female patients of childbearing potential shall have a negative serum or urine pregnancy test at screening and be willing to have additional pregnancy tests as required throughout the study. Women of non-childbearing potential (WONCBP) must not donate ova from signing informed consent until at least 6 months after the last administration of the investigational product. Please refer to Appendix 1. Males must be surgically sterile (> 6 months since vasectomy with confirmation of no viable sperm), or if engaged in sexual relations (intercourse) with a WOCBP, either his partner must be surgically sterile (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or an acceptable, highly effective contraceptive method must be used from Screening until 6 months after last IMP administration; or Males with same-sex partners (abstinence from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle; or Males must not donate sperm from the first dose of IMP until at least 90 days after the last dose of IMP.

Exclusion criteria

  • Participants will be excluded from the study for any of the following reasons:

    1. Known HER2-positive tumor by IHC.

    2. Participants with other malignancies over the past 5 years, except for cured skin basal cell carcinoma, in-situ carcinoma of the cervix, or papillary thyroid cancer.

    3. Participants who have received radiotherapy or other investigational drug or investigational therapy within 4 weeks prior to the first dose of investigational product.

    4. Participants who have undergone major surgery (except aspiration biopsy) had significant trauma within 4 weeks prior to the first dose of investigational product or required elective surgery during the study.

    5. Participants with pre-existing > Grade 1 peripheral sensory neuropathy (NCI CTCAE 5.0).

    6. Participants with known hypersensitivity to any components of the investigational product.

    7. Participants who are pregnant (positive pregnancy test) or lactating.

    8. Adverse events due to previous anti-tumor therapy have not recovered to CTCAE v5.0 Grade ≤ 1 (except for alopecia and other toxicities judged by the investigator to have no safety risk).

    9. Participants with esophageal obstruction, pyloric obstruction, intestinal obstruction, or inability to eat on their own after gastrointestinal resection, or other factors that cause difficulty in swallowing and inability to take oral drugs.

    10. Participants with symptomatic/uncontrollable central nervous system metastases or meningeal metastases, i.e., those with confirmed metastatic disease progression by examination within 2 months after radiotherapy or other local treatment, or who are ineligible for enrollment as judged by the investigator.

    11. Participants with uncontrollable bone metastases, i.e., existing or recent fracture risk, recent need for surgery or local radiotherapy, or other crisis conditions as judged by the investigator.

    12. Participants with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once monthly or more frequently).

    13. Participants with an active infection and who currently require systematic anti-infective therapy.

    14. Participants with known history of human immunodeficiency virus (HIV) infection with an exception that if they have not had an opportunistic infection within the past 12 months, they are eligible;

    15. Participants who are HBV DNA positive or HCV RNA positive.

    16. Participants with a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

      • Patients with severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention or second/third-degree atrioventricular block; patients with a mean corrected QT interval (QTcF) > 470 msec obtained from three 12-lead electrocardiograms (ECGs) at rest;
      • Patients who have had an acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade ≥ 3 cardiovascular events within 6 months before the first dose;
      • Patients with clinically uncontrollable hypertension;
      • Patients with other cardiac disorders that put the patients at a high risk as judged by the investigator;
    17. Participants with uncontrolled diabetes mellitus.

    18. Participants with a mental disorder or poor compliance.

    19. Participants also participate in another clinical study or receive other study treatments.

    20. Participants requiring concomitant use of strong CYP3A4 inhibitors or inducers or medications that prolong the QT interval in 14 days prior to the first dose of study treatment and during the study.

    21. Participants with a history of other systemic severe diseases or abnormal laboratory findings that would, in the Investigator's judgment, be inappropriate for this study.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

778 participants in 5 patient groups

Cohort 1
Experimental group
Description:
UTD2 40 mg/m2/d, po, qd, day 1-5, q3w in combination with capecitabine 1000 mg/m2, po, bid, day 1-14, q3w, and oxaliplatin 130 mg/m2/d, iv, day1, q3w, oxaliplatin will be given up to 6 cycles.
Treatment:
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Drug: Oxaliplatin
Drug: Capecitabine
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Cohort 2
Experimental group
Description:
UTD2 50 mg/m2/d, po, qd, day 1-5, q3w in combination with capecitabine 1000 mg/m2, po, bid, day 1-14, q3w, and oxaliplatin 130 mg/m2/d, iv, day1, q3w, oxaliplatin will be given up to 6 cycles
Treatment:
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Drug: Oxaliplatin
Drug: Capecitabine
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Cohort 3
Experimental group
Description:
UTD2 60 mg/m2/d, po, qd, day 1-5, q3w in combination with capecitabine 1000 mg/m2, po, bid, day 1-14, q3w, and oxaliplatin 130 mg/m2/d, iv, day1, q3w, oxaliplatin will be given up to 6 cycles
Treatment:
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Drug: Oxaliplatin
Drug: Capecitabine
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Arm A
Experimental group
Description:
UTD2 po, on d1-5, q3w (dose decided after the phase II) in combination with capecitabine 1000 mg/m2 po, bid, d1-14, q3w, and oxaliplatin 130 mg/m2/d, iv, d1, q3w, oxaliplatin will be given up to 6 cycles
Treatment:
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Drug: Oxaliplatin
Drug: Capecitabine
Drug: Utidelone Capsule
Drug: Utidelone Capsule
Arm B
Active Comparator group
Description:
Capecitabine 1000 mg/m2 po, bid, d1-14, q3w, and oxaliplatin 130 mg/m2/d, iv, d1, q3w, oxaliplatin will be given up to 6 cycles
Treatment:
Drug: Oxaliplatin
Drug: Capecitabine

Trial contacts and locations

0

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Central trial contact

Rongguo Qiu

Data sourced from clinicaltrials.gov

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