Talazoparib and Low-Dose Temozolomide in Treating Participants With Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. Evaluate the efficacy of talazoparib in combination with temozolomide as measured by
objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of talazoparib plus temozolomide as measured by progression-free
survival (PFS), overall survival, duration of response, and time to response.

II. To evaluate the safety, tolerability of talazoparib plus temozolomide. III. To evaluate
the pharmacokinetics of talazoparib when given in combination with temozolomide.

IV. To evaluate patient reported outcomes per the Patient Reported Outcomes version of the
Common Terminology Criteria for Adverse Events (PRO-CTCAE).

EXPLORATORY OBJECTIVES:

I. To identify potential biomarkers associated with response to study drug treatment.

OUTLINE:

Participants receive temozolomide orally (PO) on days 1-5 and talazoparib PO once daily (QD)
on days 1-28. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days and then up to 1
year.

Inclusion Criteria:

- Able to provide informed consent.

- Cytologically or histologically confirmed small cell lung cancer (SCLC) with
extensive-stage disease.

- Relapsed (progressed within 6 months) or refractory (progressed during or within 4
weeks of completing 1st line platinum based regimen).

- Measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

- Archival or fresh tissue biopsy available for exploratory analyses.

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1.

- Able to swallow the study drugs, has no known intolerance to study drugs or
excipients, and able to comply with study requirements.

- Female participants of childbearing potential must have a negative pregnancy test at
screening and must agree to use a highly effective birth control method (defined in
protocol) from the time of the first study drug treatment through 45 days after the
last study drug treatment.

- Male participants must use a condom when having sex from the time of the first study
drug treatment through 105 days after the last study drug treatment. Contraception
should be considered for a non-pregnant female partner of childbearing potential.

- Male and female participants must agree not to donate sperm or eggs, respectively,
from the first study drug treatment through 105 days and 45 days after the last study
drug treatment, respectively.

- Female participants may not be breastfeeding at baseline through 45 days after the
last study drug treatment.

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
dependency (within 7 days of assessment)

- Glomerular filtration rate (by Cockroft-Gault or equivalent estimation) >= 30 mL/min

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
ULN OR =< 5 X ULN for participants with liver metastases

- Serum total bilirubin =< 1.5 X upper limit or normal (ULN) OR direct bilirubin =< ULN
for participants with total bilirubin levels > 1.5 ULN

- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
participant is receiving anticoagulant therapy, as long as PT or partial
thromboplastin time (PTT) is within therapeutic range of intended use of
anticoagulants

- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless participant is
receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of
intended use of anticoagulants

Exclusion Criteria:

- Has not recovered (recovery is defined as Common Terminology Criteria for Adverse
Events (CTCAE) version (v)4 grade =< 1 or return to baseline) from the acute
toxicities of previous therapy, except treatment-related alopecia or laboratory
abnormalities otherwise meeting eligibility requirements.

- Best response of progressive disease per RECIST 1.1 to first-line platinum doublet
chemotherapy.

- Has received more than 1 line of cytotoxic therapy

- Prior immunotherapy and targeted therapies (including rovalpituzumab tesirine)
are allowed.

- Prior treatment with a PARP inhibitor (not including iniparib) or temozolomide.

- Use of antineoplastic therapies within 14 days before study treatment initiation.

- Use of any other investigational agent within 14 days before study treatment
initiation.

- Received radiation therapy within 14 day before study treatment initiation (single
fraction palliative radiotherapy is allowed without a washout).

- Prior thoracic irradiation and prophylactic cranial irradiation are allowed.

- Major surgery within 14 days before study treatment initiation.

- Diagnosis of myelodysplastic syndrome (MDS).

- Gastrointestinal disorder affecting absorption.

- Current or anticipated use of a prohibited P-gp inhibitor or P-gp inducer or BCRP
inhibitors.

- History of another cancer within 2 years before study treatment initiation, with the
exception of fully treated cancers unlikely to affect the assessment of the study
treatment safety or efficacy including early stage breast, prostate, nonmelanomatous
skin, thyroid, cervix and endometrial cancer.

- Any condition (concurrent disease, infection, or comorbidity) that interferes with
ability to participate in the study, causes undue risk, or complicates the
interpretation of safety data, in the opinion of the investigator.