A Phase I Study of Ganetespib +/- Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma

Inclusion Criteria:

- Males or females, age 18 years or older.

- Diagnosis of MM and documentation of at least 2 prior therapies which must have
included bortezomib and an immunomodulatory agent; there is no maximum number of
prior regimens.

- Patients with measurable disease defined as at least one of the following:

1. Serum M-protein ≥ 0.5 g/dl (≥5 g/l)

2. Urine M-protein ≥ 200 mg/24 h

3. Serum FLC assay: Involved FLC level ≥10 mg/dl (≥100 mg/l) and an abnormal
serum free light chain ratio (<0.26 or >1.65)

4. Measurable plasmacytoma (prior biopsy is acceptable, should be measured within
28 days of first study drug administration).

- Subject has an ECOG ≤ 2 OR Karnofsky ≥ 60% performance status.

- Females of childbearing potential*: Confirmation that the subject is not pregnant
must be established by a negative serum -human chorionic gonadotropin (-hCG)
pregnancy test result obtained during screening. Pregnancy testing is not required
for post-menopausal or surgically sterilized women. FCBP must also agree to ongoing
pregnancy testing. Men must agree to use a latex condom during sexual contact with a
FCBP even if they have had a successful vasectomy. *(FCBP - A female of childbearing
potential is a sexually mature woman who: 1) has not undergone a hysterectomy or
bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24
consecutive months).

- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (in accordance
with national and local subject privacy regulations).

- Voluntary written informed consent before performance of any study-related procedure
not part of routine medical care with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care

- Inclusion Clinical Laboratories Criteria

1. Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors
cannot be used within 7 days of first drug administration)

2. Platelet count ≥ 75 x 109/L (platelet transfusions cannot be used within 4 days
of first drug administration).

3. Hemoglobin ≥ 8.0 g/dl.

4. Serum AST or ALT ≤ 1.5 x upper limit of normal (ULN)

5. Serum creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥ 50 mL/min
(Cockcroft-Gault calculation)

6. Total bilirubin ≤ 1.5 x ULN

7. Serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN (treatment
of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to
normal with standard treatment).

Exclusion Criteria:

- Patient who have received chemotherapy, immunomodulatory drugs (e.g., lenalidomide,
thalidomide or pomalidomide), immunotherapy, radiation therapy, or any
investigational drug(s) within 14 days before enrollment or who have not recovered
from the side effects of the therapy to at least grade 1. Localized radiation
therapy to a single site within 7 days is acceptable.

- Prior therapy with an HSP90 inhibitor.

- Daily requirement for corticosteroids (except for inhalational corticosteroids);
prednisone ≤10mg/day or equivalent is permitted for other medical conditions.

- Prior peripheral stem cell transplant within 12 weeks of the first dose of study
treatment.

- Venous access devices made of materials other than silicone.

- History of severe allergic or hypersensitivity reactions to excipients (e.g.,
Polyethylene glycol [PEG] 300 and Polysorbate 80)

- Baseline QTc > 470 msec or previous history of QT prolongation while taking other
medications.

- Ventricular ejection fraction (Ef) < 50 % at baseline.

- History of documented congestive heart failure (CHF), New York Heart Association
class II/III/IV, with a history of dyspnea, orthopnea or edema that requires current
treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor
blockers, beta-blockers or diuretics. NOTE: Use of these medications for the
treatment of hypertension is allowed

- High-risk uncontrolled arrhythmias (ventricular tachycardia, high-Grade AV-block,
supra-ventricular arrhythmias which are not adequately rate-controlled) that require
current treatment with the following anti-arrythmic drugs: flecainide, moricizine or
propafenone

- History of active current coronary artery disease or unstable angina

- Peripheral neuropathy ≥ Grade 2

- Treatment with chronic immunosuppressants (e.g., cyclosporine following
transplantation)

- Uncontrolled intercurrent illness including, but not limited to, human
immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral
therapy, severe or systemic infection, , or psychiatric illness/social situations
that would limit compliance with study requirements.

- Other medications, or severe acute/chronic medical or psychiatric condition, or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration, or may interfere with the interpretation of study
results, and in the judgment of the investigator would make the subject inappropriate
for entry into this study.