Phase 1
Completed N=9
A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors
Neoplasms · Breast Neoplasms
Source: ClinicalTrials.gov NCT03343054 ↗
Enrolled (actual)
9
Serious AEs
7.1%
Results posted
Mar 2022
Primary outcomePrimary: Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) — 0; 0 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) |
0; 0 | — |
| PRIMARY Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment |
57.9 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 |
3; 6; 19 | — |
| SECONDARY Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 |
2; 3; 19 | — |
| SECONDARY Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 |
1; 2; 11 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry |
1; 2; 8; 0; 0; 1 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology |
3; 2; 8; 0; 3; 0 | — |
| SECONDARY Dose Escalation: Number of Participants With Abnormalities in Vital Signs |
1; 0; 0; 2 | — |
| SECONDARY Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib |
7.244; 13.78 | — |
| SECONDARY Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib |
0.983; 0.967 | — |
| SECONDARY Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib |
97.48; 159.1 | — |
| SECONDARY Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib |
46.55; 85.39 | — |
| SECONDARY Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) |
6.968; 5.010 | — |
| SECONDARY Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib |
551.8; 361.1 | — |
| SECONDARY Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib |
56.60; 50.73 | — |
| SECONDARY Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib |
107.5; 199.7 | — |
| SECONDARY Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib |
14.44; 32.84 | — |
| SECONDARY Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib |
2.175; 3.645 | — |
| SECONDARY Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib |
1.02; 1.03 | — |
| SECONDARY Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib |
127.2; 244.7 | — |
| SECONDARY Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) |
5.898; 4.086 | — |
| SECONDARY Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib |
2.734; 2.866 | — |
| SECONDARY Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib |
1.181; 1.249 | — |
| SECONDARY Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
0; 0 | — |
| SECONDARY Dose Escalation: Progression Free Survival (PFS) |
3.0; 3.4 | — |
| SECONDARY Dose Escalation: Duration of Response (DOR) |
— | — |
| SECONDARY Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) |
52.6 | — |
| SECONDARY Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment |
94.7; 94.7 | — |
| SECONDARY Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) |
89.5; 89.5 | — |
| SECONDARY Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment |
2.63 | — |
| SECONDARY Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) |
2.07 | — |
| SECONDARY Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment |
6.8 | — |
| SECONDARY Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) |
6.0 | — |
| SECONDARY Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment |
7.2 | — |
| SECONDARY Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) |
7.2 | — |
| SECONDARY Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12 |
0.847 | — |
| SECONDARY Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib |
3098; 3423; 2910; 3670 | — |
Eligibility Criteria
[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.
Data sourced from ClinicalTrials.gov (NCT03343054). 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.