A Phase I/II Study of Ganetespib in Combination With Doxorubicin

The dose escalation phase of the study will follow a standard 3+ 3 dose escalation scheme
with two dose levels of ganetespib (1-- mg/m2 and 150 mg/m2) administered weekly on Days 1
and 8 of a 21-day cycle, in combination with a fixed dose of doxorubicin at 50 mg/m2
administered on Day 1 alone. After 4-6 cycles of combination therapy, continuation of single
agent ganetespib will be permitted for subjects who are deriving clinical benefit.

Pharmacokinetic samples for plasma drug levels of ganetespib will be collected pre-dose and 4
hours after completion of treatment on Day 1 and Day 8 of cycle 1 only in subjects in the
dose escalation phase.

The recommended Phase II dose determined at the end of the dose escalation phase will be used
to conduct a safety dose expansion phase in relapsed/ refractory small cell lung cancer to
determine if there is a signal of efficacy in this population.

Inclusion Criteria:

- Dose escalation phase: histologically confirmed malignancy that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective. OR safety dose expansion phase: histologically or
cytologically confirmed relapsed or refractory small cell lung cancer

- No more than 3 prior lines of chemotherapy; prior therapy with doxorubicin is
permitted but no more than lifetime cumulative dose of 150 mg/m2; at least 3 weeks
since prior chemotherapy or radiotherapy; at least 6 weeks if the last regimen
included BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea) or
mitomycin C

- Age >/= 18 years

- ECOG (Eastern Cooperative Oncology Group) performance status 0-1

- Life expectancy of greater than 3 months

- Adequate organ and marrow function

- Women of child-bearing potential must agree to avoid becoming pregnant and men must
agree not to father a child for the duration of study participation.

- Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosureas or mitomycin C)
prior to entering the study or those who have not recovered from adverse events due to
agents administered more than 3 weeks earlier.

- Receiving any other investigational agents

- Untreated symptomatic brain metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ganetespib or other agents used in the study

- Receiving any medications or substances that are strong inhibitors or inducers of
CYP3A4 or CYP2C18

- Left ventricular ejection fraction < 50%

- Known serious cardiac illness or medical conditions

- uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, unstable angina pectoris, or psychiatric illness/social situations that
would limit compliance with study requirements.

- Pregnant women

- HIV-positive on combination antiretroviral therapy