Locally Advanced Pancreatic Cancer With KRAS G12D MutationPhase 2NCT07438106
A Phase II Study of HRS-4642 Combined With AG (Nab-paclitaxel and Gemcitabine) as Conversion Therapy for Locally Advanced Pancreatic Cancer
A Phase 2 study testing HRS-4642 Injection in people with Locally Advanced Pancreatic Cancer With KRAS G12D Mutation, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This study will evaluate the effectiveness and safety of HRS-4642 in combination with nab-paclitaxel and gemcitabine (AG regimen) as conversion therapy for patients with locally advanced pancreatic cancer. Participants will undergo regular assessments, including imaging scans and CA19-9 biomarker tests. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Pancreatic Cancer With KRAS G12D Mutation
- What is being tested?
- HRS-4642 Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 28 Jan 2026to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all of the following criteria to be eligible for this study:
- Age ≥18 years and ≤75 years, regardless of gender.
- Histologically or cytologically confirmed pancreatic ductal adenocarcinoma.
- Radiologically confirmed locally advanced disease, defined as:
- No distant metastasis.
- Pancreatic head/uncinate process tumors: Tumor contact with the superior mesenteric artery (SMA) >180°.
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- Pancreatic body/tail tumors: Tumor contact with the SMA or celiac artery >180°; or contact with the celiac artery with aortic invasion; or tumor invasion of the jejunal branches of the SMA.
- Inability to safely reconstruct the portal vein-superior mesenteric vein due to tumor invasion, venous occlusion, or extensive involvement of the jejunal branches of the superior mesenteric vein.
- KRAS G12D mutation confirmed by tissue histology or peripheral blood testing.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- No prior antitumor therapy (including radiotherapy, chemotherapy, targeted therapy, or immunotherapy).
- At least one radiologically measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- If biliary obstruction is present, it must have been relieved prior to study entry, and the expected survival time is >3 months.
- Signed written informed consent obtained before performing any study-related procedures.
- Adequate organ function meeting the following criteria (without corrective treatment with blood components or growth factors within 14 days prior to the first dose), with test results completed within 7 days before initiation of study treatment:
- Absolute neutrophil count (ANC) ≥1.5 × 10^9/L.
- White blood cell (WBC) count ≥3.0 × 10^9/L.
- Platelets ≥100 × 10^9/L.
- Hemoglobin >9 g/dL.
- Albumin ≥3.0 g/dL.
- Total bilirubin ≤1.5 × upper limit of normal (ULN).
- Prothrombin time and activated partial thromboplastin time ≤1.5 × ULN.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
- Serum creatinine ≤1.5 × ULN or creatinine clearance (calculated using Cockcroft-Gault formula) ≥50 mL/min.
- Electrocardiogram: QTcF interval ≤450 msec for males and ≤470 msec for females.
- Female participants of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose and must not be lactating. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 180 days after the last dose of the study drug (whichever is later). A female is considered not of childbearing potential if postmenopausal for at least 1 year, or surgically sterilized (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
Who cannot join
- Participants will be excluded from the study if they meet any of the following criteria:
- Presence of portal hypertension or cavernous transformation of the portal vein; tumor involvement of the gastrointestinal tract causing gastrointestinal bleeding; tumor leading to intra-abdominal fistula or abscess; tumor encasement of the celiac artery or superior mesenteric artery (SMA) with significant vascular wall involvement (moth-eaten appearance).
- Diagnosis of malignancies other than pancreatic cancer within 5 years prior to the first dose (excluding radically treated skin basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ).
- History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic therapy.
- Current use of systemic corticosteroid therapy (excluding topical, inhaled, nasal, or intra-articular corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first study dose. Note: Use of physiologic doses of corticosteroids (≤10 mg/day prednisone or equivalent) is permitted.
- Known history of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
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- History of allergy or hypersensitivity considered clinically significant by the investigator.
- Presence of clinically significant acute or chronic pancreatitis.
- History of drug abuse, chronic alcoholism, or infectious diseases such as AIDS (i.e., HIV-1/2 antibody positive).
- Uncontrolled active hepatitis B (defined as HBsAg positive with HBV-DNA level above the upper limit of normal at the local laboratory). Note: Participants with hepatitis B meeting the following criteria may be enrolled: 1) HBV viral load <10,000 copies/mL (2,000 IU/mL) prior to the first dose, and the participant should receive anti-HBV therapy throughout the study drug treatment period to prevent reactivation; 2) Participants who are anti-HBc positive, HBsAg negative, anti-HBs negative, and with negative HBV viral load do not require prophylactic anti-HV therapy but require close monitoring for reactivation.
- Active hepatitis C virus (HCV) infection (HCV antibody positive and HCV-RNA level above the lower limit of detection).
- Administration of a live attenuated vaccine within 28 days prior to the first study dose or anticipated need for a live attenuated vaccine during the study treatment period. Note: Administration of inactivated seasonal influenza vaccine within 28 days prior to the first dose is permitted; however, live attenuated intranasal influenza vaccines are not allowed.
- Major surgery (other than diagnostic biopsy) within 28 days prior to the first dose; minor traumatic surgery (biopsy, endoscopy, and drainage) within 7 days prior to the first dose; presence of non-healing wounds, untreated fractures.
- Presence of any severe or uncontrolled systemic disease, for example:
- Resting ECG showing significant uncontrolled abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmia, or atrial fibrillation.
- Unstable angina, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) class ≥II.
- History of any arterial thrombotic, embolic, or ischemic event within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
- Poorly controlled blood pressure (systolic >150 mmHg or diastolic >100 mmHg).
- History of non-infectious interstitial lung disease requiring glucocorticoid therapy within 1 year prior to the first dose, or current clinically active interstitial lung disease.
- Active tuberculosis.
- Active or uncontrolled infection requiring systemic therapy.
- Clinically active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction.
- Liver disease such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis.
- Low-density lipoprotein cholesterol (LDL-C) >3.4 mmol/L or severe hypertriglyceridemia (>5.7 mmol/L).
- Carotid ultrasound showing stenosis ≥50% or the presence of two or more high-risk characteristic plaques.
- History of severe infection within 28 days prior to the first dose, including but not limited to infection complications requiring hospitalization, bacteremia, or severe pneumonia; or active infection requiring therapeutic intravenous antibiotics within 2 weeks before starting study treatment. Participants receiving prophylactic antibiotics (e.g., for urinary tract infection prevention) may be enrolled.
- Any history, evidence of disease, treatment, or abnormal laboratory value that, in the investigator's judgment, could interfere with the trial results, prevent the participant from completing the study, indicate poor compliance, or pose potential risks making the participant unsuitable for study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Jiangsu Province Hospital
Nanjing
Jiang K Rong
About this study
This study will evaluate the effectiveness and safety of HRS-4642 in combination with nab-paclitaxel and gemcitabine (AG regimen) as conversion therapy for patients with locally advanced pancreatic cancer.
Participants will undergo regular assessments, including imaging scans and CA19-9 biomarker tests. If disease recurrence is suspected, unscheduled evaluations may be performed. For participants who discontinue treatment due to reasons other than disease progression (e.g., toxicity), tumor assessments will continue as scheduled until progression, loss to follow-up, death, consent withdrawal, or study termination.
After the final treatment, participants will enter a survival follow-up phase. Investigators will contact the participants or their families approximately every month (±7 days) to collect information on survival status (date and cause of death) and any subsequent anti-cancer treatments until death, loss to follow-up, study termination, or other study endpoints are met. All follow-up information will be documented in the medical records.
Read the detailed description
Study Objectives
Primary Objective:
● To evaluate the efficacy of HRS-4642 combined with AG (nab-paclitaxel and gemcitabine) as conversion therapy in patients with locally advanced pancreatic cancer, as measured by Objective Response Rate (ORR).
Secondary Objectives:
- To evaluate the efficacy of HRS-4642 combined with AG as conversion therapy by assessing surgical conversion rate, Disease Control Rate (DCR), CA19-9 response rate, Duration of Response (DOR), Progression-Free Survival (PFS), Overall Survival (OS), and 1-year OS rate.
- To evaluate the safety profile of HRS-4642 combined with AG as conversion therapy.
- To assess changes in health-related quality of life from baseline using the EORTC QLQ-C30 and EORTC QLQ-PAN26 questionnaires in all participants.
- Being tested
- HRS-4642 Injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HRS-4642 InjectionDrug
Investigational Product: HRS-4642 Injection. Dosage Form: Injection. Strength: 10 mL: 30 mg. Route of Administration: Intravenous Infusion. Manufacturer: Jiangsu Hengrui Pharmaceuticals Co., Ltd. Background: HRS-4642 is a highly potent, long-lasting, and selective KRAS G12D inhibitor developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui). It is a liposomal formulation. HRS-4642 specifically binds to KRAS G12D, thereby inhibiting the phosphorylation of MEK and ERK proteins, and exerts an antitumor effect.
| Study group | Role | What they receive |
|---|---|---|
| HRS-4642 combined with AG | Experimental | Dosing Regimen:
* HRS-4642 was administered by intravenous infusion at 480-500 mg on Day 1 and 1200 mg on Day 8 of each 21-day cycle (Q3W, every 3 weeks). The first infusion duration should be no less than 60 minutes. If no infusion-related reaction occurs after the first dose, the duration of subsequent infusions may be appropriately shortened.
* Nab-paclitaxel: 125 mg/m², intravenous infusion over 30 minutes, on Days 1 and 8, every 3 weeks.
* Gemcitabine: 1000 mg/m², intravenous infusion over 30 minutes, on Days 1 and 8, every 3 weeks. Receives: Drug: HRS-4642 Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the efficacy of HRS-4642 combined with AG (nab-paclitaxel and gemcitabine) as conversion therapy in patients with locally advanced pancreatic cancer, as measured by the Objective Response Rate (ORR).
Tumor response will be assessed by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 via computed tomography (CT) or magnetic resonance imaging (MRI) scans.
Measured: every 6 weeks(±7 days) from the first dose of study treatment until disease progression, initiation of new anti-cancer therapy, withdrawal of consent, death, or study termination, whichever occurs first, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study start28 Jan 2026
- Primary completionOct 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Pancreatic Cancer With KRAS G12D MutationStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kuirong Jiang, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07438106
- Sponsor's protocol ID
- HRS-4642-II-002
- Status last verified
- May 2026
- First submitted
- 20 Jan 2026
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of HRS-4642 Combined With AG (Nab-paclitaxel and Gemcitabine) as Conversion Therapy for Locally Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT07438106
- Acronym / sponsor ID
- HRS-4642-II-002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 28 Jan 2026 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 27 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effectiveness and safety of HRS-4642 in combination with nab-paclitaxel and gemcitabine (AG regimen) as conversion therapy for patients with locally advanced pancreatic cancer.
Participants will undergo regular assessments, including imaging scans and CA19-9 biomarker tests. If disease recurrence is suspected, unscheduled evaluations may be performed. For participants who discontinue treatment due to reasons other than disease progression (e.g., toxicity), tumor assessments will continue as scheduled until progression, loss to follow-up, death, consent withdrawal, or study termination.
After the final treatment, participants will enter a survival follow-up phase. Investigators will contact the participants or their families approximately every month (±7 days) to collect information on survival status (date and cause of death) and any subsequent anti-cancer treatments until death, loss to follow-up, study termination, or other study endpoints are met. All follow-up information will be documented in the medical records.
Detailed description
Study Objectives
Primary Objective:
● To evaluate the efficacy of HRS-4642 combined with AG (nab-paclitaxel and gemcitabine) as conversion therapy in patients with locally advanced pancreatic cancer, as measured by Objective Response Rate (ORR).
Secondary Objectives:
- To evaluate the efficacy of HRS-4642 combined with AG as conversion therapy by assessing surgical conversion rate, Disease Control Rate (DCR), CA19-9 response rate, Duration of Response (DOR), Progression-Free Survival (PFS), Overall Survival (OS), and 1-year OS rate.
- To evaluate the safety profile of HRS-4642 combined with AG as conversion therapy.
- To assess changes in health-related quality of life from baseline using the EORTC QLQ-C30 and EORTC QLQ-PAN26 questionnaires in all participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HRS-4642 combined with AG | Experimental | Drug: HRS-4642 InjectionDosing Regimen: * HRS-4642 was administered by intravenous infusion at 480-500 mg on Day 1 and 1200 mg on Day 8 of each 21-day cycle (Q3W, every 3 weeks). The first infusion duration should be no less than 60 minutes. If no infusion-related reaction occurs after the first dose, the duration of subsequent infusions may be appropriately shortened. * Nab-paclitaxel: 125 mg/m², intravenous infusion over 30 minutes, on Days 1 and 8, every 3 weeks. * Gemcitabine: 1000 mg/m², intravenous infusion over 30 minutes, on Days 1 and 8, every 3 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Age ≥18 years and ≤75 years, regardless of gender.
- Histologically or cytologically confirmed pancreatic ductal adenocarcinoma.
- Radiologically confirmed locally advanced disease, defined as:
- KRAS G12D mutation confirmed by tissue histology or peripheral blood testing.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Key exclusion criteria (27 listed)
- Presence of portal hypertension or cavernous transformation of the portal vein; tumor involvement of the gastrointestinal tract causing gastrointestinal bleeding; tumor leading to intra-abdominal fistula or abscess; tumor encasement of the celiac artery or superior mesenteric artery (SMA) with significant vascular wall involvement (moth-eaten appearance).
- Diagnosis of malignancies other than pancreatic cancer within 5 years prior to the first dose (excluding radically treated skin basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ).
- History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic therapy.
- Current use of systemic corticosteroid therapy (excluding topical, inhaled, nasal, or intra-articular corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first study dose. Note: Use of physiologic doses of corticosteroids (≤10 mg/day prednisone or equivalent) is permitted.
- Known history of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HRS-4642 InjectionInvestigational Product: HRS-4642 Injection. Dosage Form: Injection. Strength: 10 mL: 30 mg. Route of Administration: Intravenous Infusion. Manufacturer: Jiangsu Hengrui Pharmaceuticals Co., Ltd. Background: HRS-4642 is a highly potent, long-lasting, and selective KRAS G12D inhibitor developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui). It is a liposomal formulation. HRS-4642 specifically binds to KRAS G12D, thereby inhibiting the phosphorylation of MEK and ERK proteins, and exerts an antitumor effect. | Drug | HRS-4642 combined with AG |
Primary outcome
To evaluate the efficacy of HRS-4642 combined with AG (nab-paclitaxel and gemcitabine) as conversion therapy in patients with locally advanced pancreatic cancer, as measured by the Objective Response Rate (ORR).
Time frame: every 6 weeks(±7 days) from the first dose of study treatment until disease progression, initiation of new anti-cancer therapy, withdrawal of consent, death, or study termination, whichever occurs first, assessed up to 24 months
Tumor response will be assessed by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 via computed tomography (CT) or magnetic resonance imaging (MRI) scans.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HRS-4642 Injection in people with Locally Advanced Pancreatic Cancer With KRAS G12D Mutation, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jiang KUIRONG (15295779350, jiangkuirong@njmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the efficacy of HRS-4642 combined with AG (nab-paclitaxel and gemcitabine) as conversion therapy in patients with locally advanced pancreatic cancer, as measured by the Objective Response Rate (ORR). (time frame: every 6 weeks(±7 days) from the first dose of study treatment until disease progression, initiation of new anti-cancer therapy, withdrawal of consent, death, or study termination, whichever occurs first, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.