A Phase II Clinical Study of SHR-A1904 Monotherapy in Second-Line or Later Treatment of Advanced Neuroendocrine Carcinoma

A Phase II Clinical Study of SHR-A1904 in Second-Line or Later Treatment of Advanced Neuroendocrine Carcinoma

This is a prospective, single-center, phase II trial designed to evaluate the efficacy and safety of SHR-A1904 monotherapy in second-line or later treatment of advanced neuroendocrine carcinoma. The primary endpoint is the objective response rate. Secondary endpoints include progression free survival, overall survival rate, duration of response, disease control Rate and adverse event.

Inclusion Criteria:

1. Willing to join in this study, signed informed consent, good adherence, can cooperate with the follow-up;

2. Age 18-75 years old, both genders;

3. Patients with histologically confirmed advanced neuroendocrine carcinoma;

4. Progressed form previous standard therapy (at least progressed form the first line of platinum-based chemotherapy);

5. Tumor tissue samples (within 2 years or freshly obtained) must be available.

6. At least one measurable lesion that met RECIST v1.1 criteria. Measurable lesions must not have received prior local therapy such as radiotherapy;

7. ECOG Performance Status of 0-1;

8. Must have life-expectancy of ≥ 12 weeks;

9. Adequate function of marrow and major organs meets the following requirements：

   1. Blood routine (no blood transfusion or hematopoietic stimulating factor therapy within 14 days before examination)：ANC≥1.5×109/L；PLT≥100×109/L；Hb≥90 g/L;
   2. Liver function (no hepatoprotective drugs within 7 days before the examination)：ALT and AST≤3 × ULN (liver metastasis≤5.0 × ULN); TBIL≤1.5 × ULN（Gilbert's syndrome subjects：TBIL≤3mg/dL）;
   3. Renal function: Cr≤1.5 × ULN or creatinine clearance ≥60 mL / min (Cockcroft-Gault formula)；
   4. Coagulation: PT≤1.5×ULN，APTT≤1.5×ULN；
   5. Cardiac ultrasound: LVEF≥50%;

10. Female patients of childbearing age or male patients whose partner was a female of childbearing age had to consent to use a highly effective method of contraception for the duration of the study and for 6 months after the last dose of study drug; and have no plans to have children or to donate sperm or eggs, Childbearing age female patients who were not surgically sterilized had to undergo a serum pregnancy test with a negative result within 7 days before starting study treatment.；

Exclusion Criteria:

1. Previous receipt of claudin 18.2-targeted therapy;
2. Previous receipt of any drug containing a topoisomerase I inhibitor drug, including antibody-drug conjugates;
3. Merkel cell carcinoma, neuroendocrine prostate cancer, and medullary thyroid carcinoma;
4. Untreated brain metastasis, or associated with meningeal metastasis, spinal cord compression, etc. Patients who had received previous treatment for brain metastases (radiotherapy or surgery) were eligible for enrollment if they had been stable for at least 4 weeks as confirmed by imaging and had been free of systemic hormone therapy (at a dose of >10 mg per day of prednisone or the equivalent) for more than 2 weeks and were asymptomatic;
5. Spinal cord compression that could not be cured by surgery and/or radiotherapy;
6. Patients with uncontrolled cancer-related pain as judged by the investigator;
7. Patients with symptomatic pleural effusion, pericardial effusion, or ascites requiring drainage or those who had undergone therapeutic drainage of serous effusion within 2 weeks before the administration of the study drug;
8. Patients who received anti-tumor therapy such as chemotherapy within 3 weeks before the first dose of medication, or undergo a wash-out period of 5 half-lives based on the drug's pharmacokinetics, whichever is shorter;
9. Major organ surgery or major trauma within 4 weeks before the first dose of the study drug;
10. Other malignant tumors occurred within 3 years before the first treatment (except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast);
11. Patients with active interstitial lung disease, a history of interstitial lung disease or non-infectious pneumonia (any grade);
12. Unexplained fever >38.5°C before randomization (fever assessed by the investigator as tumor-related may be permitted); or severe infection (CTCAE grade >2) within 4 weeks before the first dose, such as severe pneumonia, bacteremia, or complicated infection requiring hospitalization;
13. Gastrointestinal perforation and/or fistula within 6 months prior to randomization; active gastrointestinal bleeding within 3 months prior to randomization, including but not limited to hematemesis, hematochezia, and melena, without endoscopic evidence of resolution (except for patients who underwent gastric cancer resection and whose bleeding/perforation symptoms have resolved).
14. Arterial/venous thrombotic events requiring intervention within 6 months before the first study dose, excluding catheter-related thrombosis.
15. Hypertension that is not well controlled with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); A history of hypertensive crisis or hypertensive encephalopathy;
16. Refractory nausea, vomiting, chronic gastrointestinal diseases, etc.
17. Subjects with active, known or suspected autoimmune disease (including Hiv-Positive), or a history of organ transplantation;
18. Presence of active hepatitis B or C;
19. A live or attenuated vaccine was administered within 4 weeks before the first dose of the study drug;
20. The adverse reactions of antineoplastic therapy have not recovered to NCI-CTCAE v5.0 grade ≤ 1;
21. A history of severe allergic reaction with other monoclonal antibodies or have allergic reactions to any component of SHR-A1904;
22. According to the investigator's judgment, there are other factors that may affect the results of the study or lead to the forced termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental diseases) requiring combined treatment, serious laboratory test abnormalities, accompanied by family or social factors, which will affect the safety of the subjects.