This is a multi-national, open-label, randomized, seamless phase II/III clinical study of UTD2 combined with fluoropyrimidine- and platinum-containing therapy to evaluate the efficacy and safety in patients with locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma untreated with systemic treatment in advanced setting.
Sign the informed consent form (ICF) to participate with accordance with GCP, ICH and local regulations and are willing to adhere to the study protocol.
Male and female aged ≥ 18 years as of the date of baseline visit.
Participant must have unresectable locally advanced or metastatic GC or GEJ and have histologically/pathologic confirmed predominant adenocarcinoma. The documentation of GEJ involvement can include biopsy, endoscopy, or imaging.
Phase II Study: No restriction on PD-L1 expression. Phase III study: Participant must have tumor with PD-L1 Combined Positive Score (CPS) < 1 by immunohistochemical (IHC). IHC results from site are acceptable.
Known HER2-positive tumor (HER2-positive is defined as having an IHC score of 3 +, or IHC2 + and positive HER2 expression by in situ hybridization (ISH) (refer to ASCO/CAP guidelines 2020).
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.
Participants who have received radiotherapy or other investigational drug or investigational therapy within 4 weeks prior to the first dose of investigational product.
Participants who have undergone major surgery (except biopsy) had significant trauma within 4 weeks prior to the first dose of investigational product or required elective surgery during the study.
Parallel
Utidelone Capsule
DrugUTD2 40 mg/m2/d, po, qd, day 1-5, q3w
Utidelone Capsule
Drug50 mg/m2/d, po, qd, day 1-5, q3w
Utidelone Capsule
Drug60 mg/m2/d, po, qd, day 1-5, q3w
Fluoropyrimidine- and Platinum-containing Therapy
DrugCAPOX: Capecitabine 1700 mg/m2/d, po, bid, d1-14，q3w, Oxaliplatin 130 mg/m2, iv, d1, q3w. After completing 6 times (18 weeks) of oxaliplatin treatment, the investigator may decide whether to continue oxaliplatin treatment for up to 8 times (24 weeks) based on the participant's benefits and safety. FOLFOX: Oxaliplatin 85 mg/m2, iv, d1, q2w. Folinic Acid 400 mg/m2, iv, d1, q2w, 5-FU 400 mg/m2 IV bolus d1 then 5-FU 2400 mg/m2 IV infusion over 46 to 48 hours, q2w. After completing 9 times (18 weeks) of treatment with oxaliplatin combined with folinic acid and 5-FU, the investigator may decide whether to continue FOLFOX treatment for up to 12 times (24 weeks) based on the participant's benefits and safety.
Oxaliplatin
Drug130 mg/m2/d, iv, day1, q3w, oxaliplatin will be given up to 6 cycles
Utidelone Capsule
DrugUTD2 po, on d1-5, q3w (dose decided after the phase II)
PD-1 inhibitor
DrugWhether to combine a PD-1 inhibitor will depend on the locally approved indications for the PD-1 inhibitor. If the participant's condition meets the locally approved indications for PD-1 inhibitors, the investigator may determine, in accordance with clinical guidelines, that the participant is eligible to receive treatment with UTD2 combined with fluoropyrimidine- and platinum-containing therapy, with or without a PD-1 inhibitor. If a PD-1 inhibitor is administered in combination, tislelizumab (200 mg), or pembrolizumab (200 mg), or nivolumab (360 mg), iv, day1, q3w. Alternatively, the investigator may select the dosage and administration cycle of other locally approved PD-1 inhibitors in accordance with the locally approved package inserts. The PD-1 inhibitor will be given up to 2 years.
Capecitabine
DrugCapecitabine 1700 mg/m2/d po, bid, d1-14，q3w
Capecitabine
DrugCapecitabine, 2000 mg/m2/d, po, bid, d1-14, q3w
Safety and tolerability of UTD2 and capecitabine in combination with oxaliplatin in Phase II
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)
From the first dosing until death (from any cause), follow-up began after the end of treatment
Objective Response Rate (ORR)
Response rate is the proportion of evaluable patients who are evaluated as having a CR or PR.
Progression Free Survival (PFS)
refers to the time from first dosing to the occurrence of tumor progression or death (whichever occurs first)
Maximum (or peak) serum concentration (Cmax)
Cmax of Utidelone Capsule
Time to peak drug concentration (Tmax)
Tmax of Utidelone Capsule
Patient reported outcomes (PRO)
A questionnaire derived from NCI-PRO-CTCAE version 1.0 will be used to assess patient reported safety
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