Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled
study of rolapitant in subjects receiving HEC (≥60 mg/m2 of cisplatin-based chemotherapy).
Study drug will be administered 1 - 2 hours prior to initiation of chemotherapy on Day 1.
Granisetron and dexamethasone will be administered approximately 30 minutes before
initiation of chemotherapy on Day 1,except in patients receiving taxanes as part of
cisplatin-based chemotherapy. Subjects will record all events of emesis and use of rescue
medication for established nausea and/or vomiting and will indicate the severity of nausea
they experienced in each of the previous 24 hours in the NV Subject Diary prior to HEC
administration through Day 6 in Cycle 1. Dexamethasone 8 mg twice daily (part of study
regimen) on Days 2 through 4 is NOT considered rescue therapy. Health-related quality of
life will be measured by the FLIE Questionnaire on Day 6 of Cycle 1. Safety and tolerability
will be assessed by clinical review of AEs, physical examinations including complete
neurological assessment, vital signs,electrocardiograms (ECGs), and safety laboratory values
including BUN andcreatinine. All subjects are expected to complete Cycle 1 and will have the
option of participating in up to five additional cycles. The study will investigate the
efficacy of rolapitant for the treatment of CINV during an initial chemotherapy cycle (Cycle
1).

Safety analyses will include data from Cycle 1 and from subsequent cycles. At the Screening
Visit, blood samples may be collected and stored in this study and maybe analyzed for future
biomarker research related to safety and efficacy. Analysis of these samples may include
DNA, RNA, or protein markers. The biomarker blood samples will be stored for up to 2 years
post study completion. In addition, PK samples will be collected from subjects enrolled in
selected sites.

Inclusion Criteria:

- 18 years of age or older, of either gender, and of any race

- has never been treated with cisplatin and is to receive the first course of
cisplatin-based chemotherapy (≥60 mg/m2)

- Karnofsky performance score of ≥60

- Predicted life expectancy of ≥4 months

- Adequate bone marrow, kidney, and liver function

Exclusion Criteria:

- Contraindication to cisplatin, granisetron, or dexamethasone

- Is pregnant or breast feeding

- Has previously received cisplatin or subject is planning to receive multiple days of
cisplatin in a single cycle

- Has taken the following agents within the last 48 hours 5-HT3
antagonists,Phenothiazines,Benzamides,Domperidone,Cannabinoids,NK1 antagonist,
Benzodiazepines

- Scheduled to receive any other chemotherapeutic agent with an emetogenicity level of
4 or above (Hesketh Scale) from Day 2 through Day 6, except on Day 1.

- Scheduled to receive any radiation therapy to the abdomen or pelvis from Day -5
through Day 6

- Has received systemic corticosteroids or sedative antihistamines within 72 hours of
Day 1 of the study except as premedication for chemotherapy (e.g., taxanes,
pemetrexed)

- symptomatic primary or metastatic CNS disease.

- Has ongoing vomiting, retching, clinically significant nausea caused by any etiology,
or has a history of anticipatory nausea and vomiting.

- Has vomited and/or has had dry heaves/retching within 24 hours prior to the start of
cisplatin-based chemotherapy on Day 1 in Cycle 1.