Avelumab is a human immunoglobulin (Ig)G1 monoclonal antibody (mAb) directed against
programmed death ligand 1 (PD L1). Avelumab selectively binds to PD L1 and competitively
blocks its interaction with programmed death receptor 1 (PD 1), thereby interfering with this
key immune checkpoint inhibition pathway. Avelumab is currently being investigated as single
agent and in combination with other anti cancer therapies in patients with locally advanced
or metastatic solid tumors and various hematological malignancies.
Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate [ADP] ribose)
polymerase (PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene
mutations that compromise deoxyribonucleic acid (DNA) repair, an effect referred to as
synthetic lethality, and by trapping PARP protein on DNA thereby preventing DNA repair,
replication, and transcription.
Avelumab in combination with talazoparib will be investigated in patients with locally
advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung
cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast
cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration
resistant prostate cancer (CRPC).
- Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
tumors that are not amenable for treatment with curative intent in adult patients
with: NSCLC, TNBC, HR+ breast cancer, recurrent platinum sensitive ovarian cancer, UC,
- Mandatory primary or metastatic tumor biopsy. If archival tumor tissue is available
from a biopsy/surgery the tumor tissue may be submitted without repeating a tumor
biopsy during the screening period.
- Minimum age in Japan is 20 years.
- ECOG performance status 0 or 1.
- Resolved acute effects of prior therapy
- Adequate bone marrow, renal, and liver function.
- Negative serum pregnancy test at screening.
- Male and female patients able to have children must agree to use 2 highly effective
methods of contraception throughout the study and for up to 45 days for female
patients and 105 days for male patients after the last dose.
- Signed and dated informed consent.
- Prior treatment with a PARP inhibitor.
- Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, OX 40, GITR, LAG 3, IDO, TDO,TIM 3, CTLA-4 antibody, or any other antibody
or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
Prior treatment with Sipuleucel-T for patients with mCRPC is allowed.
- Prior anti-cancer therapy within 4 weeks prior to study enrollment. Prior radiation
therapy within 2 weeks prior to enrollment. Prior palliative radiotherapy to
metastatic lesion(s) is permitted, provided it has been completed 2 days prior to
study enrollment and no clinically significant toxicities are expected (eg, mucositis,
- Major surgery within 4 weeks prior to study enrollment.
- Current use of immunosuppressive medication at the time of study enrollment.
- Known prior or suspected hypersensitivity to investigational products.
- Known history of immune mediated colitis, inflammatory bowel disease, pneumonitis,
- Active or prior autoimmune disease that might deteriorate when receiving an
- Prior organ transplantation including allogenic stem-cell transplantation.
- Vaccination within 4 weeks of study enrollment and while on trial is prohibited except
for administration of inactivated vaccines.
- Diagnosis of Myelodysplastic Syndrome.
- Patients with known brain metastases requiring steroids.
- Participation in other studies involving investigational drug(s) within 4 weeks prior
to study participation and/or during study participation.
- Persisting toxicity related to prior therapy >Grade 1
- Known HIV or AIDs-related illness.
- Positive HBV or HCV test indicating acute or chronic infection.
- Active infection requiring systemic therapy.
- Clinically significant cardiovascular disease: cerebral vascular accident/stroke or
myocardial infarction within 6 months prior to study entry; unstable angina,
congestive heart failure or a serious cardiac arrhythmia requiring medication.
- Current or anticipated use of a strong P glycoprotein (P gp) inhibitor (eg,
dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), strong P gp inducer
(eg, rifampin, ritonavir, tipranavir), or strong inhibitor of breast cancer resistance
protein (BCRP) (eg, elacridar [GF120918]).
- Other acute or chronic medical or psychiatric conditions.