Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Histologically confirmed diagnosis of advanced solid tumor for which no curative
standard treatment options exist and for which gemcitabine and cisplatin is a
suitable treatment regimen.

- After the determination of the maximum tolerated dose, an expansion cohort of 20
patients with non-small cell lung cancer whose tumors demonstrate variants in DNA
repair pathway genes will be enrolled.

- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
chest x-ray, or ≥ 10 mm with calipers by clinical exam.

- Prior treatment for this disease is allowed if it has been completed at least 2 weeks
prior to study enrollment and if all treatment-related toxicities are resolved. Prior
exposure to a PARP inhibitor is allowed for patients in the dose-finding portion of
the study.

- At least 18 years of age.

- ECOG performance status ≤ 1

- Normal bone marrow and organ function as defined below:

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Total bilirubin ≤ 1.5 x IULN

- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal

- Tissue available for sequencing (either archival tissue or readily accessible
tumor for fresh routine biopsy).

- Able to swallow tablets.

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry
and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately.

- Ability to understand and willingness to sign an IRB approved written informed
consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- A history of other malignancy ≤ 5 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only or
carcinoma in situ of the cervix.

- Received any other investigational agent within 2 weeks of starting the first dose on
study.

- Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and
previously treated. Patients must be at least 4 weeks post-brain radiation therapy.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to cisplatin, gemcitabine, talazoparib, or other agents used in
the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, active coronary artery disease, uncontrolled seizure, or psychiatric
illness/social situations that would limit compliance with study requirements.

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.

- Known HIV-positivity.