A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

A PHASE 1 STUDY OF THE SAFETY, PHARMACOKINETICS AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB, POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITOR, IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS

This is a Phase 1 study which consists of 2 parts; Dose Escalation part and Expansion part.

The dose escalation part is open-label, and evaluates safety, preliminary efficacy and PK of single-agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available.

In the dose escalation part, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs.

The expansion part is designed to assess the efficacy, safety and PK of single-agent talazoparib at RP2D determined in the dose escalation part in adult patients with locally advanced or metastatic breast cancer who have deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations.

In the expansion part, a minimum of 17 patients will be enrolled evaluable for the primary endpoint.

[Dose Escalation Part]

Inclusion Criteria:

• Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
• ECOG Performance Status 0 or 1.
• Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

• Patients with known symptomatic brain metastases requiring steroids.
• Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

[Dose Expansion Part]

Inclusion Criteria:

• Histologically or cytologically confirmed carcinoma of the breast.
• Locally advanced breast cancer that is not amenable to curative radiation or surgery and/or metastatic disease.
• Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation by Myriad Genetics' BRACAnalysis CDx test.
• No more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease.
• Have measurable lesion by the RECIST v.1.1.
• ECOG Performance Status 0-2.
• Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

• First-line locally advanced or metastatic breast cancer with no prior neoadjuvant and adjuvant chemotherapy.
• Prior treatment with a PARP inhibitor.
• Objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease.
• HER2 positive breast cancer.
• Active inflammatory breast cancer.
• Central nervous system (CNS) metastases.
• Current or anticipated use within 7 days prior to the first dose of study treatment, or anticipated use during the study of strong P-gp inhibitors.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.