Phase 1
Completed N=39
Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors
Advanced or Recurrent Solid Tumors · Breast Neoplasms · Ovarian Cancer, Epithelial · Ewing Sarcoma
Source: ClinicalTrials.gov NCT01286987 ↗
Enrolled (actual)
39
Serious AEs
39.1%
Results posted
Jan 2019
Primary outcomePrimary: Number of Participants With Objective Response — 8; 12; 2; 0 participants
Summary
This is a single-arm, open-label study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of talazoparib in patients with advanced tumors with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation phase in which the maximum tolerated dose will be defined, and a dose expansion phase.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Objective Response |
8; 12; 2; 0; 2; 0 | — |
| PRIMARY Number of Participants With Best Overall Response |
1; 1; 0; 0; 0; 0 | — |
| PRIMARY Progression-Free Survival (PFS) |
29.3; 32.1; 5.3; 6.2; 11.1; 12.1 | — |
| PRIMARY Duration of Response |
32.2; 26.9; NA; 13.6 | — |
| PRIMARY Number of Participants With Stable Disease |
7; 10; 2; 4; 4; 1 | — |
| PRIMARY Part 1: Maximum Tolerated Dose (MTD) |
1000 | — |
| PRIMARY Part 1: Recommended Part 2 Dose of Talazoparib |
1000 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor
- Must have available archived tumor tissue (formalin-fixed paraffin-embedded) [FFPE].
- 18 years of age or older.
- Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9 (pancreatic cancer).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Have adequate organ function
- Able to take oral medications.
- Willing and able to provide informed consent.
- Sexually active patients must be willing to use an acceptable method of contraception.
- Females of childbearing potential must have a negative serum pregnancy test at screening.
- Willing and able to comply with all study procedures.
Part 2 Dose Expansion Tumor Types:
- Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 4 prior regimens for metastatic disease.
- Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 2 prior regimens for metastatic disease.
- Small cell lung cancer (SCLC) patients who have received no more than one prior regimen for SCLC.
- Ewing's sarcoma patients who have received no more than 3 prior regimens for metastatic disease.
Exclusion Criteria
- Part 2 Expansion: Prior treatment with a PARP inhibitor.
- Has history of central nervous system (CNS) metastasis.
- Exception: In patients with SCLC, history of adequately treated brain metastasis who do not require corticosteroids for management of CNS symptoms.
- Has had major surgery within 28 days before Cycle 1, Day 1.
- Has active peptic ulcer disease.
- Active gastrointestinal tract disease with malabsorption syndrome.
- Pregnant or breastfeeding at screening or planning to become pregnant (in each case, either oneself or one's partner) at any time during the study.
Data sourced from ClinicalTrials.gov (NCT01286987). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.