HRS-4642 With Nimotuzumab and Chemotherapy for First-line Treatment of Advanced Pancreatic Cancer Patients

NCT06770452 | Recruiting Phase 2

• 1 other identifier: CAPT04
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a single-arm phase II clinical study to include 32 patients with advanced pancreatic cancer with KRAS G12D mutation to evaluate the effectiveness of HRS-4642 combined with nitutuzumab and AG for first-line treatment of advanced pancreatic cancer.

Conditions

Metastatic Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective reponse rate (ORR)

  The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during the whole study

  Up to 2 years

Secondary Outcomes (4)

• Duration of remission （DoR）

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Progression-free survival （PFS）

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

Study Arms (1)

Arm A

EXPERIMENTAL

Eligible patients will receive HRS-4642, combined with Nimotuzumab and AG regimen, predose regimen: HRS-4642 500mg intravenous infusion, D1,1200mg IV infusion, D8, every 3 weeks; Nimotuzumab 400mg intravenous infusion, D1,8, every 3 weeks; Albumin paclitaxel 125mg/m2 intravenous infusion, gemcitabine 1000mg / m2, D1,8, a cycle every 3 weeks until disease progression or toxicity intolerance.

Drug: HRS-4642; Drug: Nimotuzumab; Drug: gemcitabine + nab-paclitaxel

Interventions

HRS-4642 DRUG

HRS-4642 is a KRAS G12D inhibitor

Arm A

Nimotuzumab DRUG

Nimotuzumab is a humanized IgG 1 monoclonal antibody targeting EGFR

Arm A

gemcitabine + nab-paclitaxel DRUG

Albumin paclitaxel 125mg/m2 intravenous infusion, gemcitabine 1000mg / m2, D1,8, a cycle every 3 weeks

Arm A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-75 (including 18 and 75); 2.Metastatic pancreatic cancer (from pancreatic ductal epithelium); 3.Tumor tissue contains KRAS G12D mutation; 4.No systemic antitumor therapy in advanced stage; if previous neoadjuvant / adjuvant therapy, last treatment should be over 6 months; 5.At least one measurable lesion according to the RECIST v1.1 criteria; 6.The ECOG (Eastern Cooperative Oncology) score was 0-1; 7.Expected survival period of 3 months; 8.The functions of vital organs meets the following requirements (any blood components, cell growth factors are not allowed 2 weeks prior to enrollment):
• Neutrophil count≥1.5×10\^9 / L;
• Platelet≥100×10\^9 / L;
• Hemoglobin≥100 g / L;
• Serum albumin≥30 g / L;
• Total bilirubin≤1.5×ULN; ALT, AST≤3×ULN and ALP≤2.5×ULN; if the patient has liver metastasis, ALT, ALT and AST≤5×ULN; if the patient has liver or bone metastasis, ALP≤5×ULN;
• Creatinine clearance≥50 mL/min or serum creatinine ≤1.5×ULN;
• Urinary protein \<2+; if urine protein≥2+, an additional 24 hours urine protein quantification should be tested, and if 24 hours urine protein quantification \<1g can be enrolled;
• ECG: QTcF≤450 ms (male), QTcF≤470 ms (female);
• Cardiac color ultrasound: LVEF (left ventricular ejection fraction) ≥50%; 9.Women of childbearing age must have a blood pregnancy test within 7 days before enrollment, the result should be negative and must be non-lactating and should be willing to use appropriate contraception during the trial and within 6 months of treatment. For men, surgical sterilization or consent to use appropriate contraception during the study and within 6 months after completion of treatment.
• Volunteer to participate in the study and sign the informed consent form, good compliance, agreed to cooperate with the follow-up.

You may not qualify if:

• Previous treatment:
• Previous treatment of targeted therapy against KRAS G12D.
• Previous targeted therapy against EGFR.
• Received major surgery or major trauma within 4 weeks before enrollment, or palliative local treatment (including but not limited to palliative radiotherapy, interventional therapy) within 2 weeks prior to enrollment.
• Have received any other clinical study medication within 4 weeks before enrollment, except for an observational (non-interventional) clinical study or interventional clinical study follow-up.
• (5)14 days before enrollment with drugs that strongly inhibit or induce the hepatic drug-metabolizing enzymes CYP3A4 or CYP2C8.
• The presence of a central nervous system (CNS) metastases. 3.Acute or chronic pancreatitis requiring clinical intervention. 4.Symptoms and signs of gastrointestinal obstruction or obstruction within 6 months before initiation of study treatment but can be screened if surgery is performed and the obstruction is completely resolved.
• Within 2 weeks prior to enrollment, there is a third space effusion (such as a large amount of pleural fluid, ascites, etc.) that can not reach the stable state (no intervention treatment is needed after the removal of the drainage tube), and only a small amount of effusion on imaging and without clinical symptoms can be enrolled.
• Severe infection occurred within 4 weeks before enrollment, such as severe pneumonia, bacteremia, infectious complications, requiring hospitalization; fever of unknown cause\> 38.5℃ within 2 weeks before enrollment (fever caused by the tumor according to the investigator); 2 weeks of enrollment (except in cases of prophylactic antibiotics).
• Severe cardiovascular and cerebrovascular disease. 8.Patients with known or suspected interstitial pneumonia except only interstitial changes on imaging.
• Prior history of clear neurological or psychiatric disorders, including epilepsy and dementia.
• Presence of non-healing wounds (severe, non-healing or split), uncured fractures.
• Adverse events due to prior treatment prior to enrollment did not return to NCI-CTCAE level 1 (except for alopecia and enrollment criteria; except AEs not affecting the study medication).
• Malignant tumors other than the primary tumor within the 5 years before enrollment, except those with low risk of metastasis and death: adequately treated cervical carcinoma in situ, skin basal cells or squamous cell carcinoma, etc.
• Combined with active hepatitis B (hepatitis B surface antigen positive and HBV DNA 500 IU / mL), hepatitis C (hepatitis C antibody positive, and HCV-RNA above the lower limit of detection of the analytical method). Those known to have acquired immunodeficiency syndrome or test positive for HIV, and those infected with active syphilis. Subjects with active tuberculosis or a history of active tuberculosis infection within 48 weeks before screening, with or without treatment.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (2)

First Affiliated Hospital of Zhejiang University Schlool of Medicine

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

nimotuzumab; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Tingbo Liang, MD

CONTACT

86+19941463683; liangtingbo@zju.edu.cn

Yiwen Chen, MD

CONTACT

86+15088682641; cherry0705@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 13, 2025
• Study Start: March 25, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

CN (2)