GnP Combined With SHR-1701 and Apatinib as First-Line Treatment for Locally Advanced or Metastatic PDAC

GnP Combined With SHR-1701 and Apatinib as First-Line Treatment for Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma: A Single-Center, Open-Label, Phase Ib/II Trial

The goal of this clinical trial is to evaluate the safety and efficacy of GnP combined with SHR-1701 and Apatinib as first-line treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Pancreatic Cancer; Locally Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: SHR-1701; Drug: Apatinib; Drug: gemcitabine; Drug: Nab-paclitaxel

Detailed Description

This study is a prospective, single-arm, single-center, phase Ib/II clinical trial evaluating the safety and efficacy of GnP combined with SHR-1701 and Apatinib as first-line treatment in patients with locally advanced or metastatic pancreatic cancer.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dan Cao; Phone Number: +8618980605963; Email: caodan@scu.edu.cn
• Study Contact Backup: Name: Min Ren

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
      • Contact: Dan Cao; Phone Number: +8618980605963; Email: caodan@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1) Age 18-75 years, regardless of sex; 2) patients with histologically confirmed pancreatic ductal adenocarcinoma (PDAC); 3) previously untreated patients with unresectable locally advanced or metastatic PDAC, with at least one measurable lesion according to RECIST v1.1, and target lesions must not have received prior radiotherapy or local treatment; 4) ECOG performance status of 0-1; 5) life expectancy ≥3 months; 6) willingness to comply with study procedures and able to receive treatment and undergo follow-up; 7) adequate major organ function, with laboratory test results meeting the following criteria within 7 days before enrollment: white blood cell (WBC) count ≥2.5×10⁹/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet (PLT) count ≥75×10⁹/L, hemoglobin (HGB) ≥90 g/L (without blood transfusion or erythropoietin [EPO] dependence within 7 days), total bilirubin (TBIL) ≤1.5× the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN, albumin ≥30 g/L, international normalized ratio (INR) ≤1.5×ULN, serum creatinine (Cr) ≤1.5×ULN, and urinary protein ≤1+; 8) patients who are hepatitis B surface antigen (HBsAg)-positive with a peripheral blood hepatitis B virus DNA (HBV-DNA) level ≤1×10³/L; patients who are HBsAg-positive with a peripheral blood HBV-DNA level ≥1×10³/L may also be eligible if, in the investigator's judgment, chronic hepatitis B is clinically stable and does not increase the patient's risk; 9) voluntary participation in the study and provision of written informed consent.

Exclusion Criteria:

1) Known hypersensitivity to any study drug; 2) known or suspected central nervous system metastases, defined as signs or symptoms suggestive of CNS metastasis, unless CNS metastasis has been excluded by CT or MRI; 3) history of other malignancies within 5 years, except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix; 4) requiring any concomitant anticancer treatment other than the study treatment during the study, including chemotherapy, targeted therapy, hormonal therapy, immunotherapy, radiotherapy, or traditional Chinese medicine with antitumor activity; 5) prior or current treatment with chemotherapy, FAK inhibitors, or antibodies targeting PD-1, PD-L1, PD-L2, CD137, or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), including ipilimumab or any other antibody or drug targeting T-cell costimulatory or checkpoint pathways; 6) diagnosis of immunodeficiency or chronic systemic corticosteroid therapy (prednisone >10 mg/day or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment; 7) receipt of a live vaccine within 30 days before the first dose of study treatment, including but not limited to measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccines; inactivated seasonal influenza vaccines are permitted, whereas live attenuated vaccines such as intranasal influenza vaccines (e.g., FluMist) are not permitted; 8) uncontrolled hypertension, defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg despite treatment; 9) significant cardiac disease, including congestive heart failure (NYHA class III-IV), previous myocardial infarction, or uncontrolled angina within 6 months; 10) clinically significant arrhythmias requiring treatment, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation, or ECG abnormalities confirmed on repeat examination that, in the investigator's judgment, require clinical intervention or treatment; 11) history of hemorrhagic or thromboembolic events within the past 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or spontaneous major tumor-related bleeding; 12) surgery required within 28 days before or anticipated within 28 days after the last dose of study treatment; 13) uncontrolled third-space fluid accumulation, such as large pleural effusion or ascites; 14) definite gastrointestinal bleeding tendency within 4 weeks before the first dose, including: ① active localized ulcerative lesions with positive fecal occult blood; ② melena or hematemesis within 28 days; or ③ positive fecal occult blood in patients with unresected tumor invasion of the gastrointestinal tract who, in the opinion of the principal investigator at the study center, may be at risk of major gastrointestinal bleeding; 15) previous gastrointestinal perforation or suspected risk of gastrointestinal perforation, or intestinal obstruction; 16) concomitant medications that, in the investigator's judgment, are required during the trial and may affect the metabolism of the investigational drug, such as strong CYP3A4 inhibitors or inducers, or drugs with a narrow therapeutic index that are primarily metabolized by CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2D6; 17) severe psychiatric disorders; 18) women who are pregnant, breastfeeding, or potentially pregnant; 19) women or men of childbearing potential unwilling to use effective contraception during the study and for 3 months after the last dose of study treatment; 20) participation in another clinical trial of a drug or medical device within 4 weeks before enrollment; 21) any other condition that, in the investigator's judgment, makes the patient unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SHR-1701 combined with Apatinib and GnP

Drug: SHR-1701; SHR-1701 is administered by intravenous infusion at a dose of 30 mg/kg once every 3 weeks (Q3W). The dose may be adjusted to the recommended phase II dose (RP2D) determined during the phase Ib safety run-in phase.; Drug: Apatinib; Apatinib is administered orally at a dose of 250 mg once daily (QD). The dose may be adjusted to the recommended phase II dose (RP2D) determined during the phase Ib safety run-in phase.; Drug: gemcitabine; Gemcitabine is administered by intravenous infusion at a dose of 1000 mg/m² on days 1 and 8 of each 3-week cycle.; Drug: Nab-paclitaxel; Nab-paclitaxel is administered by intravenous infusion at a dose of 125 mg/m² on days 1 and 8 of each 3-week cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase II Dose (RP2D)	RP2D will be determined on the basis of evaluation on safety and efficacy data in Phase Ib.	through phase I study completion, an average of 5 months
Objective Response Rate (ORR)	Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.	through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the first administration of study treatment to death from any cause. Participants who are alive or lost to follow-up at the time of analysis will be censored at the date of their last known survival assessment.	through study completion, an average of 2 years
Progression-Free Survival (PFS)	Time from the first administration of study treatment to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first. Participants who are alive and have not experienced disease progression will be censored at the date of the last tumor assessment.	through study completion, an average of 2 years
Disease Control Rate (DCR)	Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) as the best overall response according to RECIST v1.1 criteria.	through study completion, an average of 2 years
Duration of Response (DOR)	Time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.	through study completion, an average of 2 years
Time to Progression (TTP)	Time from the first administration of study treatment to the first documented disease progression according to RECIST v1.1 in the ITT population. Participants who have not experienced disease progression at the time of analysis will be censored at the date of the last tumor assessment.	through study completion, an average of 2 years
R0 Resection Rate	Proportion of participants in the ITT population who undergo surgical resection and achieve R0 resection, defined as complete macroscopic tumor removal with no microscopic residual tumor at the resection margin.	through study completion, an average of 2 years
Incidence of Treatment-Related Adverse Events (TRAEs)	Incidence and severity of adverse events considered by the investigator to be related to study treatment, graded according to NCI-CTCAE version 5.0.	through study completion, an average of 2 years
Incidence of Serious Adverse Events (SAEs)	Incidence of serious adverse events, including events resulting in death, life-threatening events, hospitalization or prolongation of hospitalization, persistent or significant disability, congenital anomaly, or other medically important events.	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Principal Investigator: Dan Cao, Division of Abdominal Tumor, Department of Medical Oncology, Cancer Center and State Key Laboratory of Biological Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan

Study record dates

Study Major Dates

• Study Start (Estimated): September 10, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: August 26, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 3, 2026

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Apatinib; Locally advanced pancreatic cancer; Metastatic pancreatic cancer; SHR-1701; GnP
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; 130-nm albumin-bound paclitaxel; apatinib; SHR-1701
• Other Study ID Numbers: SHR1701-IIT-PDAC001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to privacy protection requirements, regulatory restrictions in China, and limitations in the original informed consent process that did not include provisions for external data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No