Fosrolapitant and Palonosetron for Highly Emetogenic ADC-Induced Nausea and Vomiting in Solid Tumors

Inclusion Criteria：

1. Age ≥18 years, either sex;
2. Pathologically confirmed malignant solid tumors;
3. Planned to receive initial highly emetogenic ADC therapy on a 3-week regimen;
4. Expected survival ≥3 months;
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
6. Adequate organ function, meeting the following criteria:

   1. Neutrophil count ≥1.5 × 10⁹/L;
   2. Hemoglobin ≥90 g/L;
   3. Platelet count ≥100 × 10⁹/L;
   4. Total bilirubin ≤1.5 × ULN;
   5. In patients without known liver metastases, aspartate aminotransferase ≤2.5 × ULN and/or alanine aminotransferase ≤2.5 × ULN (for patients with liver metastases, this may be relaxed to ≤5 × ULN);
   6. Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min;
   7. ECG: QTc ≤450 ms (male), QTc ≤470 ms (female);
   8. Echocardiography: left ventricular ejection fraction (LVEF) ≥50%;
7. Female subjects of childbearing potential, and male subjects whose partners are women of childbearing potential, must use a highly effective method of contraception from the signing of the informed consent form until 35 days after the last dose; sperm donation is not permitted during the study. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 h before randomization and must be non-lactating. Subjects must clearly understand and voluntarily participate in this study and personally sign the informed consent form.

Exclusion Criteria

1. Received, within 7 days before randomization, or planned to receive during the treatment period, abdominal radiotherapy (including at or below the diaphragmatic plane), pelvic radiotherapy, whole-body radiotherapy, or whole-brain radiotherapy;
2. Planned to receive highly emetogenic chemotherapy from Day 2 after ADC administration until the next treatment;
3. Prior use of other ADC drugs;
4. Use of medications with potential antiemetic efficacy within 2 days before the start of study treatment: first-generation 5-HT3 receptor antagonists (e.g., ondansetron), phenothiazines (e.g., prochlorperazine), butyrophenones (e.g., haloperidol), benzamides (e.g., metoclopramide), domperidone, cannabinoids, traditional Chinese medicines with potential antiemetic effects, scopolamine, cyclizine, etc.;
5. Initiation of benzodiazepines or opioids within 2 days before the start of study treatment (except triazolam, temazepam, or midazolam administered alone daily);
6. Initiation of morphine within 7 days before the start of study treatment (except those receiving a stable dose);
7. Receipt of systemic corticosteroid therapy (including but not limited to dexamethasone, hydrocortisone, methylprednisolone, or prednisolone) or sedating antihistamines (e.g., diphenhydramine) within 7 days before the start of study treatment (Note: single-dose steroids for prevention of contrast allergy and topical or inhaled administration are permitted);
8. Use of palonosetron within 14 days before the start of study treatment;
9. Use of NK-1 receptor antagonists within 28 days before the start of study treatment;
10. Use of specific CYP3A4 substrates (terfenadine, cisapride, astemizole) or CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, ketoconazole or itraconazole, diltiazem, etc.) within 7 days before the start of study treatment, or use of strong CYP3A4 inducers (e.g., phenobarbital, rifampin, phenytoin, carbamazepine, etc.) or specific CYP2D6 substrates (thioridazine, pimozide) within 28 days before randomization;
11. Vomiting and/or retching, or nausea, within 24 h before the start of study treatment;
12. Symptomatic brain metastases or any symptoms suggestive of brain metastases or intracranial hypertension;
13. Inadequately controlled serous cavity effusion, including pleural effusion, ascites, and pericardial effusion (those controlled after treatment and stable for ≥2 weeks may be enrolled);
14. Severe cardiovascular disease within 3 months before the start of study treatment, including but not limited to acute myocardial infarction, unstable angina, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association \[NYHA\] class II-IV), or history of serious cardiac conduction abnormalities (e.g., torsades de pointes);
15. Poorly controlled hypertension before the start of study treatment (two consecutive resting systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg);
16. Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL), active hepatitis C (HCV-Ab positive and HCV-RNA ≥ upper limit of normal), acquired immunodeficiency syndrome (AIDS) or HIV-positive, or syphilis-positive;
17. Concomitant disease that precludes dexamethasone administration, such as active infection (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction, etc.);
18. Known contraindications to NK-1 receptor antagonists, 5-HT3 receptor antagonists, or dexamethasone;
19. Participation in another clinical trial within 30 days before the start of study treatment (based on use of study drug);
20. Other circumstances considered by the investigator to make participation in this study inappropriate.