A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting

Inclusion Criteria:

Cycle 1

- Signed written informed consent

- Histologically or cytologically confirmed solid tumor malignancy.

- Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be
permitted.

- Scheduled to receive at least 4 repeated consecutive cycles of the following highly
emetogenic reference chemotherapies (HEC), alone or in combination with other
chemotherapeutic agents on Day 1: cisplatin administered as a single IV dose of ≥ 70
mg/m2; cyclophosphamide ≥1500 mg/m2; carmustine (BCNU) >250mg/m2; dacarbazine (DTIC);
mechloretamine (nitrogen mustard)

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 .

- If a patient is female, she shall be of non-childbearing potential or of childbearing
potential using reliable contraceptive measures and having a negative urine pregnancy
test.

- Hematologic and metabolic status adequate for receiving an highly emetogenic regimen
based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes,
Serum Creatinine or Creatinine Clearance)

- Able to read, understand, follow the study procedure and complete patient diary.

Cycles 2 to 4:

The following inclusion criteria must be checked prior to inclusion at each repeated cycle:

- Participation in the study during the next cycle of chemotherapy is considered
appropriate by the Investigator and does not pose unwarranted risk to the patient.

- Scheduled to receive the same chemotherapy regimen as Cycle 1 or one of the reference
chemotherapies as defined in Inclusion criterion 5 for Cycle 1.

- If a patient is female, she shall be of non--childbearing potential or of childbearing
potential using reliable contraceptive measures and having a negative urine pregnancy
test.

- Adequate hematologic and metabolic status according to the Investigator's opinion.

Exclusion Criteria:

Cycle 1

- Lactating woman.

- Active infection or uncontrolled disease except for malignancy that may pose
unwarranted risks in administering the study drugs to the patient.

- Current use of illicit drugs or current evidence of alcohol abuse.

- Scheduled to receive moderately or highly emetogenic chemotherapies from Day 2 to Day
5.

- Received or is scheduled to receive radiation therapy to the abdomen or the pelvis
within 1 week prior to the start of the reference chemotherapy administration on Day 1
or between Days 1 to 5.

- Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute)
within 24 hours prior to the start of the reference chemotherapy administration on Day
1.

- Symptomatic primary or metastatic CNS malignancy.

- Known hypersensitivity or contraindication to 5-HT3 receptor antagonists, to
dexamethasone or to NK-1 receptor antagonists.

- Known contraindication to the IV administration of 50 mL 5% glucose solution.

- Previously received an NK-1 receptor antagonist.

- Participation in a previous clinical trial involving IV pro-netupitant or oral
netupitant administered alone or in combination with palonosetron.

- Any investigational drugs (other than those given in this study) taken within 4 weeks
prior to Day 1, and/or is scheduled to receive any investigational drug during the
present study.

- Systemic corticosteroid therapy at any dose within 72 hours prior to the start of
reference chemotherapy administration on Day 1. Topical and inhaled corticosteroids
are permitted.

- Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.

- Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1
week prior to Day 1.

- Scheduled to receive any of the following CYP3A4 substrates within 1 week prior to Day
1: terfenadine, cisapride, astemizole, pimozide.

- Received within 4 weeks prior to Day 1 or scheduled to receive any CYP3A4 inducer.

- Any medication with known or potential antiemetic activity within 24 hours prior to
the start of reference chemotherapy administration on Day 1 of Cycle 1, including but
not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists

- History or predisposition to cardiac conduction abnormalities, except for incomplete
right bundle branch block

- History of Torsade de Point or known history of risk factors for Torsade de Point
(heart failure, hypokalemia, family history of Long QT Syndrome).

- Severe cardiovascular diseases diagnosed within 3 months prior to Day 1 of first
cycle, including myocardial infarction, unstable angina pectoris, significant valvular
or pericardial disease, history of ventricular tachycardia, symptomatic Congestive
Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, and severe
uncontrolled arterial hypertension.

- Any illness or condition that, in the opinion of the Investigator, may confound the
results of the study or pose unwarranted risks in administering the investigational
product to the patient.

- Concurrent medical condition that would preclude administration of dexamethasone such
as systemic fungal infection or uncontrolled diabetes.

Cycles 2 to 4:

The following exclusion criteria must be checked prior to inclusion in each repeated cycle:

- Lactating woman.

- Active infection or uncontrolled disease except for malignancy that may pose
unwarranted risks in administering the study drugs to the patient.

- Started any of the restricted medications.

- Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute)
within 24 hours prior to the start of reference chemotherapy administration on Day 1.

- Received or is scheduled to receive radiation therapy to the abdomen or the pelvis
within 1 week prior to the start of the reference chemotherapy administration on Day 1
or between Days 1 to 5.

- Symptomatic primary or metastatic CNS malignancy.