HRS-4642 Combined With Nimotuzumab in the Treatment of Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma

Inclusion Criteria:

1. Male and female subjects aged 18-75 years (including 18 and 75 years).

2. Pancreatic ductal adenocarcinoma confirmed by pathology (histology) or cytology.

3. Patients with metastatic pancreatic ductal adenocarcinoma.

4. At the time of study enrollment, according to the solid tumor efficacy evaluationcriteria (RECIST1.1), imaging diagnosis had at least one measurable lesion (lesiondiameter ≥10 mm and lymph node diameter ≥15 mm according to CT or MRI evaluation).

5. Physical condition score ECOG score 0-2 points.

6. Expected survival ≥ 12 weeks.

7. Major organ function is normal.

8. The AE caused by previous anti-tumor therapy must be restored to the level of ≤grade 1 (CTCAE v5.0) or the level specified in the inclusion criteria. If theinvestigator determines that NCI-CTCAE≤ grade 2 and there is no safety risk to thesubject, the participant can be enrolled, such as receiving immune checkpointinhibitor therapy. Subjects with type 1 diabetes and hypothyroidism that are stableafter hormone replacement therapy.

9. Fertile female subjects must undergo a serum pregnancy test within 7 days before thefirst dose, and the result is negative; And must be non-lactating. Fertile femalesubjects and male subjects whose partners are women of reproductive age must agreeto comply with the contraceptive requirement from the time of signing the informedconsent until 30 days after the final administration of the trial drug (for subjectsreceiving HRS-4642);

10. The subjects voluntarily joined the study and signed the informed consent, with goodcompliance and follow-up.

Exclusion Criteria:

Patients will not be admitted to the study if they meet any of the following criteria:

1. The patient had previously used KRAS inhibitors or targeted EGFR therapy.

2. known allergy to the investigational drug or any of its components.

3. Systemic antitumor therapy (including unmarketed investigational drugs ortherapies), such as chemotherapy, targeted therapy, and immunotherapy, has beenreceived within 28 days prior to first administration, except for the following:oral fluorouracil and small-molecule targeted drugs within 14 days prior to firstadministration of investigational drugs or within 5 half-lives of drugs (whicheveris longer). Chinese medicines with anti-tumor indications should be used within 14days before the first use of the investigational drug; Surgical treatment (exceptdiagnostic surgery) within 28 days prior to initial dosing; Patients who receivedlocal treatment such as radiotherapy, intervention or ablation within 14 days beforethe first dose.

4. Previous or concurrent suffering from other malignant tumors, Unless it is for basalcell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma ofthe skin, cervical carcinoma in situ, local prostate cancer, ductal carcinoma insitu of the breast after radical surgery, papillary carcinoma of the thyroid (allowing hormone therapy for non-metastatic prostate cancer or breast cancer) thathas achieved complete remission at least 2 years prior to screening and does notrequire or is not expected to require other treatment during the study period;

5. accompanied by untreated or active central nervous system (CNS) tumor metastasis.Subjects with a history or current history of meningeal metastasis. Participants maybe enrolled if their CNS metastases have been adequately localized (surgery orradiation) and do not require hormone therapy, and neurological recovery to baseline (except for lingering signs or symptoms associated with CNS treatment) is at least 2weeks prior to initial treatment.

6. Patients with severe cardiovascular and cerebrovascular thromboembolism (e.g.,myocardial infarction, unstable angina pectoris, stroke), NYHA grade 2 or abovecardiac dysfunction, and clinically significant supratrioventricular or ventriculararrhythmias requiring clinical intervention in the 6 months prior to study entry.

7. Study the presence of digestive tract obstruction or signs and symptoms of digestivetract obstruction within 6 months prior to the start of treatment, but screening canbe performed if surgical treatment has been performed, and the obstruction has beencompletely resolved.

8. Bleeding events of esophageal and gastric varices caused by portal hypertensionoccurred within 3 months before the first administration.

9. Had undergone a gastroscopy within 3 months prior to the first dose indicatingsevere (G3) varicose veins that were untreated or did not recover after treatment;There is current portal hypertension (including imaging evidence of splenomegaly)and the investigator determined that admission to the study would cause a greaterrisk of bleeding.

10. Advanced patients who are symptomatic, have spread to the internal organs, and areat risk of developing life-threatening complications in the short term (includingpatients with uncontrolled large exudates [chest, pericardium, abdominal cavity]);If effusion drainage is performed, patients who have been stable for at least 2weeks after drainage can be enrolled in the group (local treatment within the serouscavity is allowed according to the diagnosis and treatment routine before signingthe information).

11. Known or suspected pulmonary disease such as interstitial lung disease,non-infectious pneumonia, COPD, pulmonary embolism or other serious and uncontrolledmedical disease, acute infection, recent history of major surgery (within 28 days orhave not recovered from side effects).

12. Patients who had active tuberculosis infection within 1 year before enrollment orhad a history of active tuberculosis infection more than 1 year before but had notreceived formal treatment.

13. Patients with congenital or acquired immune deficiency, such as humanimmunodeficiency virus (HIV) infection, active hepatitis B (HBV surface antigen [HBsAg] test positive during screening and HBV-DNA test value ≥10000 copies /ml [2000 IU/ml]), Active hepatitis C (positive for HCV antibody [HCV-AB] and HCV RNAduring screening) or co-infection with hepatitis B and hepatitis C.

14. Acute or chronic pancreatitis with significant clinical significance; Patients athigh risk for pancreatitis, such as those with serum amylase and/or lipaseconcentrations ≥3 ULN.

15. Use of live attenuated vaccine within 28 days prior to the initial studyadministration, or anticipated use of live attenuated vaccine during the studytreatment.

16. Participated in a clinical trial of any drug or medical device within 4 weeks priorto initial dosing.

17. The presence of uncontrollable mental illness and other circumstances known toaffect the completion of the study procedure, such as alcohol, drug or substanceabuse, and criminal detention.

18. Other situations that the researchers believe should not be included.