Evaluating the Efficacy and Safety of HSK21542 Injection in Chemotherapy-induced Nausea and Vomiting

A Multicenter, Randomized, Double-blind, Active-Controlled Dose-Finding Study of HSK21542 Injection for the Prevention of Chemotherapy-induced Nausea and Vomiting (CINV)

This is a multicenter, randomized, double-blind, active-controlled dose-finding study. About 180 subjects who receive a high emetic chemotherapy are planned to be enrolled and randomized into three groups by a ratio of 1:1:1.

Inclusion Criteria:

1.18 years of age or older, of either gender;

2. Has never been treated with chemotherapy regimen and plan to receive asingle day high emetic chemotherapy regimen by intravenous infusion，including but not limited to AC regimen, carboplatin AUC ≥ 4, Camustine>250 mg/m2, cisplatin, and other treatment options;

3. Diagnosed with a malignant solid tumor by histology or cytology;

4. Has an ECOG Performance Status of 0 or 1;

5. Predicted life expectancy of ≥3 months;

6. Adequate bone marrow, kidney, and liver function:

1. Absolute neutrophil count ≥ 1.5 × 109/L, white blood cell count ≥ 3.0 × 109/L;

2. Platelet count ≥ 75 × 109/L;

3. Hemoglobin ≥ 70 g/L;

4. Aspartate transaminase (AST) ≤ 3 × ULN (≤ 5 × ULN in patients with hepatocellular carcinoma or liver metastasis);

5. Alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 × ULN in patients with hepatocellular carcinoma or liver metastasis);

6. Serum total bilirubin ≤ 2 × ULN (≤ 3 × ULN for patients with hepatocellular carcinoma or liver metastasis);

7. Creatinine ≤ 2 × ULN;

   7. Subjects who agree to participate in the trial and voluntarily sign the Informed Consent Form (ICF);

Exclusion Criteria:

1. History or evidence of any of the following diseases prior to screening:

   1. Suffering from primary or metastatic malignant tumors of the central nervous system;
   2. Suffering from epilepsy, Parkinson's disease, or other central nervous system disorders that cause nausea and vomiting;
   3. Suffering from intestinal obstruction or other digestive system diseases that may cause nausea and vomiting as determined by researchers;
   4. Suffering from clearly diagnosed vestibular dysfunction other than motion sickness (including but not limited to peripheral vestibular syndrome, central vestibular syndrome, etc.);
   5. History of obvious and chronic dizziness;
   6. QT interval>450 ms during screening or taking concomitant medications due to prolonged QT interval or has risk factors for QT interval prolongation or correspon;

2. Allergies or contraindications to the study drugs or other drugs specified in the protocol (including chemotherapy drugs, investigational drugs and mimetics, dorasetron, aripipitan, dexamethasone, etc.) ;

3. Subjects who have experienced nausea, retching, or vomiting before 24 hours of randomization;

4. Subjects who have received abdominal or pelvic radiation therapy within the first 7 days of randomization or plan to receive abdominal or pelvic radiation therapy during the study period;

5. Subjects with a history of drug abuse, drug addiction, or alcoholism within 3 months prior to screening, where alcoholism is defined as consuming >2 units of alcohol on average daily (1 unit = 360 mL of beer with 5% alcohol, 45 mL of liquor with 40% alcohol or 150 mL of wine);

6. Subjects who have participated in any investigational trial (defined as receiving investigational drug or placebo) within 1 month prior to screening;

7. Female subjects who are pregnant or breastfeeding; female or male subjects of child-bearing potential are unwilling to use contraception throughout the entire study period and for 3 months after the study completion;

8. Subjects judged by the investigator to be unsuitable for participating in this clinical trial for any other factors.