Advanced Pancreatic Adenocarcinoma
Conditions
Brief summary
The Phase Ib/II study is an open-label, single-arm, multicenter trial designed to assess the efficacy and safety of Y101D in combination with Gemcitabine and Albumin Paclitaxel as first-line systemic treatment for advanced pancreatic cancer patients. The Phase Ib portion of the study aims to evaluate the safety of escalating doses of Y101D in combination with the standard regimen of Gemcitabine and Albumin Paclitaxel and determine the recommended phase 2 dose (RP2D). The Phase II portion of the study aims to evaluate the effectiveness of this combination treatment in a small population of patients.
Detailed description
A total of 57-81 systemic treatment-naïve patients with advanced pancreatic cancer will be enrolled in the study. Phase Ib will enroll 12-36 patients to assess the safety of Y101D combined with Gemcitabine and Albumin Paclitaxel at doses of 20mg/kg or 30mg/kg. The recommended phase 2 dose (RP2D) for Y101D in combination with the other drugs will be determined based on the safety profile and preliminary efficacy data. Following determination of the RP2D, Phase II will enroll a total of 40-45 patients to evaluate the effectiveness of the combination treatment using the RP2D of Y101D. The primary endpoint of the Phase II study will be the objective response rate. Secondary endpoints will include progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety profiles. Pharmacodynamic parameters such as serum tumor biomarkers and TGF-β concentration will also be evaluated. Overall, the study aims to assess the safety, efficacy, and pharmacodynamics of Y101D in combination with Gemcitabine and Albumin Paclitaxel as a first-line systemic treatment for advanced pancreatic cancer patients.
Interventions
DRUGY101D
Intravenous infusion of Y101D at day1, combined with Gemcitabine and Nab-Paclitaxel IV infusion at day1, 8, a 21-day cycle. After 6 cycles, Y101D and Gemcitabine infusion is applied as the maintenance treatment.
Sponsors
Wuhan YZY Biopharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with pancreatic cancer (including ductal adenocarcinoma and acinar cell carcinoma) confirmed by histology or cytology; and evidence of unresectable or distant metastasis. * No prior systemic treatment for advanced/metastatic pancreatic cancer. * Previous use of anti-tumor Chinese herbal medicine or traditional Chinese medicine preparations, but discontinued use at least 28 days before the first administration of the investigational drug. * According to RECIST 1.1 criteria, the subject must have at least one measurable target lesion confirmed by CT or MRI examination that has not been locally treated (unless the target lesion has clearly progressed). * Expected survival time ≥ 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. * According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, any toxicity from previous anti-tumor treatment or surgery must have recovered to grade 0-1 or to the level specified by the inclusion/
Exclusion criteria
. Note: Exclusions include alopecia, pigmentation changes, ≤ grade 2 neuropathy, hypothyroidism due to hormone replacement, or other adverse events confirmed to have become chronic. * Organ function levels must meet the following requirements: Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelets (PLT) ≥ 100 × 109/L, hemoglobin (HGB) ≥ 90g/L (within 14 days before screening without blood transfusion, use of blood products, or correction with granulocyte colony-stimulating factor \[G-CSF\] or other hematopoietic growth factors). Liver function: Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal, aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times the upper limit of normal (if there is liver metastasis, AST and ALT up to 5 times the upper limit of normal are allowed). Renal function: Serum creatinine (Cr) ≤ 1.5 times the upper limit of normal or creatinine clearance rate ≥ 50 mL/min (Cockcroft-Gault formula). Coagulation function: International normalized ratio (INR) ≤ 1.5, prothrombin time (PT), and activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | From the time of the first dose (Day 1) until Day 21 | Dose limiting toxicities during the first 21 days after the first administrations of Y101D in each cohort. |
| RP2D | From the enrollment of first patient through phae 1b study completion, an average of 1 year | Recommended Phase 2 Dose of Y101D |
| Objective Response Rate (ORR) | From the time of first dosing (Day 1) until disease progression (up to 6 months) | Objective Response Rate assessed according to RECIST 1.1 per investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Serum Concentration (Cmax) | From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months). | The highest Y101D concentration in serum during one treatment cycle (21 days) |
| Trough Serum Concentration (Ctrough) | From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months). | The lowest Y101D concentration in serum during one treatment cycle (21 days) |
| Area under the serum concentration versus time curve (AUC) during one treatment cycle (21 days) | From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months). | The area under the serum concentration versus tiem curve of Y101D during one treatment cycle (21 days) |
| The TGF-β concentration in serum | From the time of first dosing (Day 1) until disease progression or death or toxicity intolerance (up to 6 months). | The TGF-β concentreation in serum at 30 minutes before the first treatment dosing of Y101D and the subsequent dosing of Y101D every two cycles (Cycle 3 Day 1, Cycle 5 Day 1, etc.) until the disease progression or death or toxicity intolerance of Y101D. |
| The CA19-9 concentration in serum | From the time of first dosing (Day 1) until disease progression or death or toxicity intolerance (up to 6 months). | The CA19-9 concentreation in serum at 30 minutes before the first treatment dosing of Y101D and the subsequent dosing of Y101D every two cycles (Cycle 3 Day 1, Cycle 5 Day 1, etc.) until the disease progression or death or toxicity intolerance of Y101D. |
| The positive rate of Anti-Drug Antibody (ADA) and Neutralizing antibody (Nab) | From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months) | The potivie rate of Anti-Drug Antibody and neutralizing antibody in serum 30 minutes before the Y101D infusion at Day 1 of Cycle 1, Cycle 2, Cycle 4 and Cycle 7 (a 21-day cycle). |
| Disease control rate (DCR) | From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months). | Disease control rate assessed according to RECIST 1.1 per investigator |
| Duration of response (DOR) | From the time of first dosing (Day 1) until one month after the EOT | The time from the first objective response to disease progression or death |
| Progression-free survival (PFS) | From the time of first dosing (Day 1) until disease progression or death (up to 12 months). | The time from the first objective response to disease progression or death (Up to 12 months) |
| Overall survival (OS) | From the time of first dosing (Day 1) until death (up to 2 years). | The time from the first objective response to death (Up to 2 yrs) |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORTao Zhang, MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed