Phase II Study of Cabazitaxel-XRP6258 in Advanced Non-Small Cell Lung Cancer

A substantial number of patients with lung cancer progress after first line treatment and
require second line chemotherapy. Lung cancer appears to account for 40-50% of all known
brain metastasis. The incidence of brain metastases among lung cancer patients ranges from
16-20%. Chemotherapy has had limited utility due to problems crossing the blood brain
barrier.

Currently there are three drugs approved by the FDA for second line treatment of NSCLC but
each has distinct toxicities. Cabazitaxel-XRP6258 is a potent novel taxane with enhanced
activity against an increased number of cell lines including lung, prostate, colon,
pancreas, head and neck, kidney, gastric, glioblastoma, and melanoma. It also has the
ability to cross the blood brain barrier. Cabazitaxel-XRP6258 was found to have an improved
antiproliferative activity than other chemotherapy agents against insensitive cell lines.
The Phase I studies of Cabazitaxel-SRP6258 have determined dosage and schedule
recommendations in advanced NSCLC patients to be utilized for a Phase II multicenter study.

Subjects will be placed on one of two schedules (A or B) each with a specified dosage and
administration schedule. All subjects will be followed for survival/progression after every
2 cycles of therapy with imaging studies. A two stage design will be used for each of the
two schedules. Fourteen subjects will be accrued for each schedule in the first stage with
possible accrual of an additional 34 subjects per schedule depending upon the first stage
results.

Inclusion Criteria:

- Histologic or cytologic diagnosis of NSCLC (squamous or non-squamous or NSCLC-not
specified)

- Subjects who have failed first line chemotherapy (platinum doublets or non- platinum
doublets [previous taxane exposure is allowed]) for Stage IV NSCLC.

- Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors
(RECIST)

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Age > 18 years old

- Adequate bone marrow, liver and renal function, defined as:

- Absolute neutrophil count (ANC) greater than or equal to 1500/ul

- Hemoglobin greater than or equal to 10 g/dl

- Platelet count greater than or equal to 100,000/ul

- Total bilirubin less than or equal to 1.5 x upper limit of normal (except in
subjects with documented Gilbert's syndrome)

- AST/ALT less than or equal to 1.5 x upper limit of normal

- Serum creatinine less than or equal to 1.8 mg/dl

- Fully recovered from any previous surgery (at least 4 weeks since major surgery)

- Fully recovered from previous radiation therapy (at least 2 weeks)

- All subjects must agree to practice approved methods of birth control (if
applicable). A negative pregnancy test must be documented during the screening period
for women of childbearing potential.

- Written informed consent and authorization to use and disclose health information
(HIPAA) must be signed by the subject.

- Subjects with symptomatic brain metastases should be adequately treated and
controlled prior to the initiation of the study. Subjects with asymptomatic brain
metastases will be allowed in the study without any prior therapy for brain
metastases.

Exclusion Criteria:

- Concurrent cancer chemotherapy, biologic therapy or radiotherapy

- Administration of any investigational agent within 28 days prior to administration of
current therapy

- Untreated symptomatic brain metastases

- Greater than or equal to Grade 2 neuropathy

- Concurrent serious infection

- Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor,
which is likely to compromise subject safety and affect the outcome of the study.

- Treatment for a cancer other the NSCLC within 5 years prior to enrollment, with the
exception of basal cell carcinoma or carcinoma in situ of the cervix

- Any evidence of history of hypersensitivity for the taxane class of chemotherapy
drugs

- History of positive serology for HIV

- Psychiatric disorder that prevents subjects from providing informed consent or
following protocol instructions

- Pregnant or lactating women