Efficacy of a Maintenance Treatment With TALAzoparib Following First Line Platinum-based Chemotherapy in Malignant MESOthelioma

Inclusion Criteria:

• Patients older than 18 years old

• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2

• Histologically - or cytologically - confirmed malignant mesotheliomas: epithelioid,sarcomatoid, biphasic

• Developed from pleura (cohort A) or from peritoneum (cohorts B1 and B2)

• Previously treated with first-line platinum based-chemotherapy (including minimum onecycle of pemetrexed) for 4 to 6 cycles, with no sign of disease progression duringchemotherapy.

• No previous treatment with bevacizumab and PARP inhibitor

• Minimum 6 weeks and maximum 8 weeks interval between last chemotherapy cycle andtalazoparib start

• For pleural mesotheliomas (cohort A), primary or interval debulking surgery with orwithout hyperthermic intrapleural or intrathoracic chemotherapy (HITHOC) will beauthorized, in the case of non-complete cytoreductive surgery only

• For peritoneal mesotheliomas

• In cohort B1, primary or interval debulking surgery ± hyperthermicintraperitoneal chemotherapy (HIPEC) will be authorized in the case ofnon-complete cytoreductive surgery (CC2 or CC3) only. This cohort will alsoinclude patients with non-operated diseases

• In cohort B2, complete macroscopic (CC0 or CC1) primary or interval debulkingsurgery ± HIPEC will be required. Intraperitoneal treatment with pressurized intraperitoneal aerosol chemotherapy sessions (PIPAC) are not allowed.

• Measurable or non-measurable (but radiologically evaluable) disease as per modifiedRECIST version 1.1 on computed tomography (CT) scan (within 28 days of talazoparibinitiation)

• Availability at the study site of a representative FFPE tumor sample in a block or atleast 30 unstained slides from biopsy or surgery specimen, aged less than 6 months.

• Patients with adequate bone marrow function measured within 28 days prior toadministration of study treatment as defined below:

• Absolute neutrophil count ≥1.0 x 109 /L

• Platelet count ≥50 x 109 /L

• Haemoglobin ≥8.0 g/dL (may have been blood transfused)

• Patients with adequate renal function:

• Calculated Glomerular Filtration Rate (GFR) ≥30 ml/min/1.73 m2 according to CKD-EPIformula

• Patients with adequate hepatic function

• Total bilirubin ≤ 1 × upper limit of normal [ULN] and aspartate aminotransferase (AST) > ULN

• Total bilirubin > 1.0 to1.5 × ULN and any AST

• Patients must have a life expectancy ≥16 week.

• Confirmation of non-childbearing status (pregnancy test) for women of childbearingpotential.

• A highly effective method of contraception is required for female patients duringtreatment of talazoparib, and for at least 7 months after completing therapy. Advisemale patients with female partners of reproductive potential and pregnant partners touse a condom, during treatment with talazoparib and for at least 4 months after thefinal dose.

• Patients who gave its written informed consent to participate to the study.

• Patients affiliated to a social insurance regime.

• Patients are willing and able to comply with the protocol for the duration of thestudy including undergoing treatment and scheduled visits and examinations includingfollow up.

Exclusion Criteria:

• Uncontrolled intercurrent illness, including but not limited to, such as congestiveheart failure; respiratory distress; liver failure; allergy, or psychiatricillness/social situations that would limit compliance with study requirement accordingto the investigator, substantially increase risk of incurring AEs or compromise theability of the patient to give written informed consent.

• Patients with second primary cancer, except: adequately treated non-melanoma skincancer, curatively treated in-situ cancer of the cervix, or other solid tumourscuratively treated with no evidence of disease for ≥5 years.

• All subjects with brain metastases or meningeal involvement.

• Patients receiving any systemic chemotherapy, radiotherapy (except for palliativereasons), within 6 weeks from the last dose prior to study treatment (or a longerperiod depending on the defined characteristics of the agents used). The patient canreceive a stable dose of bisphosphonates for bone metastases, before and during thestudy as long as these were started at least 4 weeks prior to treatment with studydrug.

• Persistent toxicities (CTCAE ≥grade 2) with the exception of alopecia and sensoryneuropathy, caused by previous cancer therapy.

• Treatment with other investigational agents.

• Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or othergastro-intestinal disorder that does not allow oral medication such as malabsorption.

• Known severe hypersensitivity reactions to PARP inhibitors.

• Known HIV or AIDS related illness.

• Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCVantibody tested positive).

• Treatment with oral anticoagulant anti-vitamin K such Coumadin®

• Prior organ transplantation, including allogeneic stem cell transplantation (excludingautologous bone marrow transplant).

• Patients under guardianship.

• Women who are breastfeeding (during treatment with talazoparib and for at least 1month after the final dose)

• Participation in other interventional clinical research that may interfere with theexperimental drugs efficacy.