A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors

Pfizer

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Advanced Solid Tumors; Ovarian Cancer; Solid Tumors; Prostate Cancer; Colorectal Cancer; Pancreatic Cancer; NSCLC

Treatments: Drug: Talazoparib soft gel capsule; Drug: TALZENNA capsule

Study type: Interventional

Funder types: Industry

Identifiers

NCT04672460

2020-006101-35 (EudraCT Number)

C3441037

Details and patient eligibility

About

This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple dosing under fasting conditions in participants with advanced solid tumors. In addition, the effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be evaluated in fixed sequence after the 2 BE assessment periods.

Enrollment: 73 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Histological diagnosis of recurrent, locally advanced or metastatic solid tumor that is not amenable for treatment with curative intent.

   • Solid tumors with known or likely pathogenic germline or somatic tumor gene defect (eg, one or more BRCA1 or BRCA2 gene defect except for ovarian cancer) that would benefit from PARPi therapy per current approvals for the tumor indication or supported by strong scientific evidence.
   • Received at least 1 prior SOC regimen, if it exists, as appropriate for the respective tumor type unless deemed unsuitable or declined these therapies; ovarian cancer participants must have at least 1 prior cytotoxic chemotherapy regimen, including at least 1 course of platinum-based therapy. Participants must not have had disease progression within 6 months of initiation of platinum containing regimen.

2. ECOG performance score of 0-1.

3. Adequate bone marrow function:

   • ANC ≥1500 cells/mm3
   • Platelets ≥100,000 cells/mm3
   • Hemoglobin ≥10.0 g/dL

4. Adequate organ functions:

   • CLCR ≥60 mL/min and no documented CLCR <60 mL/min and no change in CLCR >25% in the past 4 weeks
   • AST and ALT ≤2.5 × ULN; if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤5 × ULN;
   • Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert's syndrome);

Exclusion Criteria

1. For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
2. Toxicities from previous anti-cancer therapies must be resolved to NCI CTCAE <Grade 2, except for alopecia, sensory neuropathies ≤Grade 2, or other Grade ≤2 AEs not constituting a safety risk, based on investigator's judgment, are acceptable.
3. Diagnosed with MDS or AML.
4. Active infection requiring systemic therapy within 2 weeks of enrollment.
5. Any condition in which active bleeding or pathological conditions may carry a high risk of bleeding (eg, known bleeding disorder, coagulopathy or tumor involvement with major vessels).
6. Known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment. Asymptomatic brain metastases currently not undergoing treatment are allowed.
7. Known history of testing positive for HIV, AIDS, positive HBV surface antigen, positive HCV RNA, or positive COVID-19 viral test. Asymptomatic patients with no active infection detected but positive antibody tests, indicating past infection, are allowed.
8. Current or anticipated use of P-gp inhibitors, BCRP inhibitors, and P-gp inducers within 2 weeks or 5 half-lives prior to randomization (whichever is longer) .

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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73 participants in 2 patient groups

Sequence 1

Experimental group

Description:

Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.

Treatment:

Drug: TALZENNA capsule

Drug: Talazoparib soft gel capsule

Drug: Talazoparib soft gel capsule

Sequence 2

Experimental group

Description:

Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.

Treatment:

Drug: TALZENNA capsule

Drug: Talazoparib soft gel capsule

Drug: Talazoparib soft gel capsule