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

Phase 2

Not yet recruiting

• Conditions: Gastric or Gastroesophageal Junction Adenocarcinoma
• Interventions: Drug: Utidelone Capsule; Drug: Capecitabine; Drug: Oxaliplatin

• Registration Number: NCT06841679
• Lead Sponsor: Beijing Biostar Pharmaceuticals Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-10
• Study First Submitted QC: 2025-02-18
• Last Update Submitted: 2025-02-18
• Study First Posted: 2025-02-24
• Last Update Posted: 2025-02-24
• Study Start: 2025-05-01
• Primary Completion: 2030-09-01
• Study Completion: 2030-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 778

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Utidelone Capsule	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.
Cohort 2	Utidelone Capsule	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
Cohort 2	Capecitabine	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
Cohort 2	Oxaliplatin	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
Cohort 1	Capecitabine	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.
Cohort 1	Oxaliplatin	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.
Cohort 3	Capecitabine	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
Cohort 3	Oxaliplatin	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
Cohort 3	Utidelone Capsule	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
Arm A	Capecitabine	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
Arm A	Oxaliplatin	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
Arm A	Utidelone Capsule	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
Arm B	Capecitabine	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
Arm B	Oxaliplatin	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

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of UTD2 and capecitabine in combination with oxaliplatin in Phase II	From Day 1 to Day 21	dose limiting toxicity (DLT), defined as any toxicity meeting the criteria outlined in the protocol during Cycle 1 in a 21-days cycle
Overall Survival (OS)	12 months	From the first dosing until death (from any cause), follow-up began after the end of treatment

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	12 months	Response rate is the proportion of evaluable patients who are evaluated as having a CR or PR.
Maximum (or peak) serum concentration (Cmax)	12 months	Cmax of Utidelone Capsule
Progression Free Survival (PFS)	12 months	refers to the time from first dosing to the occurrence of tumor progression or death (whichever occurs first)
Time to peak drug concentration (Tmax)	12 months	Tmax of Utidelone Capsule
the area under the concentration-time curve from dosing (time 0) to time t (AUC0-t)	12 months	the AUC0-t of Utidelone Capsule
the area under the concentration-time curve from time zero to infinity (AUCinf)	12 months	the AUC0inf of Utidelone Capsule
the time required for plasma concentration of a drug to decrease by 50% (t1/2)	12 months	the t1/2 of Utidelone Capsule
Treatment-emergent Adverse Events (TEAE)	Until 28 days after the last dose of treatment	Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event version 5.0 (CTCAE v5.0)