A Trial Of Y101D In Combination With Gemcitabine And Albumin Paclitaxel In Patients With Advanced Pancreatic Cancer

Study Overview

A Trial of Y101D in Combination With Gemcitabine and Albumin Paclitaxel in Patients With Advanced Pancreatic Cancer

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.

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.

Advanced Pancreatic Adenocarcinoma

DRUG: Y101D

Y101D03

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-01-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-07-16
First Submitted that Met QC Criteria 2024-02-11	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-07-20
First Posted (ACTUAL) 2024-02-20	Results First Posted N/A	Last Verified 2025-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Experimental group Y101D combined with Gemcitabine and Nab-Paclitaxel	DRUG: Y101D 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Experimental group

Y101D combined with Gemcitabine and Nab-Paclitaxel

DRUG: Y101D

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.

Primary Outcome Measures	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs)	Dose limiting toxicities during the first 21 days after the first administrations of Y101D in each cohort.	From the time of the first dose (Day 1) until Day 21
RP2D	Recommended Phase 2 Dose of Y101D	From the enrollment of first patient through phae 1b study completion, an average of 1 year
Objective Response Rate (ORR)	Objective Response Rate assessed according to RECIST 1.1 per investigator	From the time of first dosing (Day 1) until disease progression (up to 6 months)

Secondary Outcome Measures	Measure Description	Time Frame
Peak Serum Concentration (Cmax)	The highest Y101D concentration in serum during one treatment cycle (21 days)	From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Trough Serum Concentration (Ctrough)	The lowest Y101D concentration in serum during one treatment cycle (21 days)	From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Area under the serum concentration versus time curve (AUC) during one treatment cycle (21 days)	The area under the serum concentration versus tiem curve of Y101D 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 TGF-β concentration in serum	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.	From the time of first dosing (Day 1) until disease progression or death or toxicity intolerance (up to 6 months).
The CA19-9 concentration in serum	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.	From the time of first dosing (Day 1) until disease progression or death or toxicity intolerance (up to 6 months).
The positive rate of Anti-Drug Antibody (ADA) and Neutralizing antibody (Nab)	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).	From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months)
Disease control rate (DCR)	Disease control rate assessed according to RECIST 1.1 per investigator	From the time of first dosing (Day 1) until disease progression or toxicity intolerance (up to 6 months).
Duration of response (DOR)	The time from the first objective response to disease progression or death	From the time of first dosing (Day 1) until one month after the EOT
Progression-free survival (PFS)	The time from the first objective response to disease progression or death (Up to 12 months)	From the time of first dosing (Day 1) until disease progression or death (up to 12 months).
Overall survival (OS)	The time from the first objective response to death (Up to 2 yrs)	From the time of first dosing (Day 1) until death (up to 2 years).

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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:

Patients diagnosed with central nervous system (CNS) metastasis confirmed by imaging.
Patients with diseases associated with a high risk of clinically significant gastrointestinal bleeding (such as tumor invasion of the gastrointestinal tract or bile ducts) or any other condition or history related to severe bleeding.
Presence of clinically uncontrollable third-space fluid accumulation before the first administration of the investigational drug, such as pleural effusion, ascites, or pericardial effusion that cannot be controlled by drainage or other methods, as determined by the investigator.
Underwent major surgery within 4 weeks prior to the first administration of the investigational drug (excluding needle biopsies and tooth extractions).
Use of immunosuppressive drugs within 7 days prior to the first administration of the investigational drug, excluding nasal and inhaled corticosteroids or physiological doses of systemic corticosteroid hormones
Significant clinical pancreatitis.
History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
Presence of active clinical infection of grade 2 or higher (according to CTCAE v5.0 criteria) at screening, requiring systemic (oral or intravenous) antimicrobial treatment.
Patients requiring long-term use of steroids or immunosuppressive agents for conditions such as active autoimmune diseases or post-organ transplant maintenance therapy. Exceptions include type 1 diabetes, hypothyroidism that can be controlled by replacement therapy alone, and skin diseases (such as vitiligo, psoriasis, or alopecia) that do not require systemic treatment.
Severe respiratory system diseases or patients judged by the investigator to be unsuitable for inclusion, or patients with concomitant interstitial pneumonia.
Average corrected QT interval (QTcF) >450 msec (males) or >470 msec (females) based on three electrocardiogram (ECG) examinations during screening (repeat testing and averaging of three measurements are required only if the first ECG indicates QTcF >450 msec [males] or >470 msec [females]). History of long or short QT syndrome in the family or individual, or significant cardiovascular diseases within 6 months before screening.
History of non-study malignancy (excluding non-invasive lesions with extremely low risk of recurrence, such as squamous cell carcinoma and basal cell carcinoma of the skin, cervical carcinoma in situ, or breast carcinoma in situ) within 5 years prior to the first administration of the investigational drug.
Active hepatitis B (positive hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb], peripheral blood HBV DNA titers <500 IU/mL allow inclusion), active hepatitis C, active syphilis, HIV-positive patients.
Pregnant or lactating women, or individuals with reproductive potential within 6 months after the end of this clinical study, regardless of gender.
Known history of substance abuse or drug addiction.
History of clear neurological or psychiatric disorders, as determined by the investigator, that would hinder compliance with treatment or adherence to instructions.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Tao Zhang, MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record