Prescription Drug Information: Talzenna (Page 3 of 4)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been conducted with talazoparib.

Talazoparib was clastogenic in an in vitro chromosomal aberration assay in human peripheral blood lymphocytes and in an in vivo bone marrow micronucleus assay in rats. This clastogenicity is consistent with genomic instability resulting from the primary pharmacology of talazoparib, indicating the potential for genotoxicity in humans. Talazoparib was not mutagenic in a bacterial reverse mutation (Ames) test.

Fertility studies in animals have not been conducted with talazoparib. In repeat-dose toxicity studies up to 3-months duration, talazoparib-related findings in the testis and epididymis at doses ≥0.04 mg/kg/day in rats and ≥0.01 mg/kg/day in dogs included decreased organ weights, luminal cellular debris, reduced sperm, and degeneration/atrophy. These doses in rats and dogs resulted in approximately 1.0 times and 0.2 times, respectively, the exposure (AUC) in humans at the recommended dose. Follicular atresia of the ovary was observed in rats at doses ≥1 mg/kg/day talazoparib, approximately 9.5 times the AUC in patients at the recommended dose.

14 CLINICAL STUDIES

EMBRACA Study (NCT01945775)

Deleterious or Suspected Deleterious Germline BRCA-mutated (gBRCAm) HER2-negative Locally Advanced or Metastatic Breast Cancer

EMBRACA (NCT01945775) was an open-label study in which patients (N=431) with gBRCAm HER2-negative locally advanced or metastatic breast cancer were randomized 2:1 to receive TALZENNA 1 mg or healthcare provider’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine) until disease progression or unacceptable toxicity. Randomization was stratified by prior use of chemotherapy for metastatic disease (0 versus 1, 2, or 3), by triple-negative disease status (triple-negative breast cancer [TNBC] versus non-TNBC), and history of central nervous system (CNS) metastasis (yes versus no).

Patients received no more than 3 prior cytotoxic chemotherapy regimens for their metastatic or locally advanced disease. Patients were required to have received treatment with an anthracycline and/or a taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting. First-line treatment for advanced or metastatic disease with no prior adjuvant chemotherapy was allowed if the investigator determined that 1 of the 4 chemotherapy choices in the control arm would be an appropriate treatment option for the patient. Patients with prior platinum therapy for advanced disease were required to have no evidence of disease progression during platinum therapy. No prior treatment with a PARP inhibitor was permitted. Of the 431 patients randomized in the EMBRACA study, 408 (95%) were centrally confirmed to have a deleterious or suspected deleterious gBRCAm using a clinical trial assay; out of which 354 (82%) were confirmed using the BRACAnalysis CDx®. BRCA mutation status (breast cancer susceptibility gene 1 [BRCA1] positive or breast cancer susceptibility gene 2 [BRCA2] positive) was similar across both treatment arms.

The median age of patients treated with TALZENNA was 45 years (range 27 to 84) and 50 years (range 24 to 88) among patients treated with chemotherapy. Among all randomized patients, 1% versus 2% were males, 67% versus 75% were White; 11% versus 11% were Asian, and 4% versus 1% were Black or African American in the TALZENNA and chemotherapy arms, respectively. Almost all patients (98%) in both arms had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Approximately 56% of patients had estrogen receptor-positive and/or progesterone receptor-positive disease; 44% of patients had triple-negative disease, and the proportions were balanced across both treatment arms. Fifteen percent (15%) of patients in the TALZENNA arm and 14% of patients in the chemotherapy arm had a history of CNS metastases. Ninety-one percent (91%) of patients in the TALZENNA arm had received prior taxane therapy, and 85% had received prior anthracycline therapy in any setting. Sixteen percent (16%) of patients in the TALZENNA arm and 21% of patients in the chemotherapy arm had received prior platinum treatment in any setting. The median number of prior cytotoxic regimens for patients with advanced breast cancer was one; 38% received no prior cytotoxic regimens for advanced or metastatic disease, 37% received one, 20% received two, and 5% received three or more prior cytotoxic regimens.

The major efficacy outcome measure was progression-free survival (PFS) evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by blinded independent central review (BICR). A statistically significant improvement in PFS was demonstrated for TALZENNA compared with chemotherapy. A sensitivity analysis of investigator-assessed PFS was consistent with the BICR-assessed PFS results. Consistent PFS results were observed across patient subgroups defined by study stratification factors (line of therapy, TNBC status, and history of CNS metastases). The overall survival (OS) data were not mature at the time of the final PFS analysis (38% of patients had died). Efficacy data from the EMBRACA study are summarized in Table 5, and the Kaplan-Meier curves for PFS are shown in Figure 1.

Table 5. Summary of Efficacy Results – EMBRACA Study
TALZENNAChemotherapy
Abbreviations: BICR=blinded independent central review; CI=confidence interval.
*
Hazard ratio is estimated from a Cox proportional hazards model stratified by prior use of chemotherapy for metastatic disease (0 versus 1, 2, or 3), by triple-negative disease status (triple-negative breast cancer [TNBC] versus non TNBC), and by history of central nervous system metastasis (yes versus no).
P-values from stratified log-rank test (2-sided).
Conducted in intent-to-treat (ITT) population with measurable disease at baseline.
§
Response rate based on confirmed responses.
Median estimated from Kaplan-Meier probabilities.
Progression-Free Survival by BICRN=287N=144
Events, number (%)186 (65)83 (58)
Median months (95% CI)8.6 (7.2, 9.3)5.6 (4.2, 6.7)
Hazard Ratio (95% CI)*0.54 (0.41, 0.71)
p-value p<0.0001
Patients with Measurable Disease by Investigator N=219N=114
Objective Response Rate, % (95% CI)§50.2 (43.4, 57.0)18.4 (11.8, 26.8)
Duration of Response Median months (95% CI)6.4 (5.4, 9.5)3.9 (3.0, 7.6)

Figure 1. Kaplan-Meier Curves of PFS – EMBRACA Study

Figure 1
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16 HOW SUPPLIED/STORAGE AND HANDLING

TALZENNA is supplied in strengths and package configurations as described in Table 6:

Table 6. TALZENNA Capsules
Package Configuration Capsule Strength (mg) NDC Print
Bottles of 30 capsules 0.25 NDC: 0069-0296-30 Ivory cap (printed with “Pfizer” in black) and a white body (printed with “TLZ 0.25″ in black).
Bottles of 30 capsules 1 NDC: 0069-1195-30 Light red cap (printed with “Pfizer” in black) and a white body (printed with “TLZ 1″ in black).

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

  • MDS/AML: Advise patients to contact their healthcare provider if they experience weakness, feeling tired, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness, blood in urine or stool, and/or laboratory findings of low blood cell counts, or a need for blood transfusions. This may be a sign of hematological toxicity or a more serious uncommon bone marrow problem called MDS or AML, which have been reported in patients who received PARP inhibitors [see Warnings and Precautions (5.1)].
  • Myelosuppression: Advise patients that TALZENNA may affect hematopoiesis and can cause anemia, leukopenia/neutropenia, and/or thrombocytopenia [see Warnings and Precautions (5.2)].
  • Administration Instructions: Advise patients that TALZENNA can be taken once daily with or without food. Instruct patients that if they miss a dose of TALZENNA, they should take their next normal dose at the usual time. Also advise patients to swallow each capsule whole, and that capsules must not be opened or dissolved [see Dosage and Administration (2.2)].
  • Embryo-Fetal Toxicity: Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of the pregnancy [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with TALZENNA and for at least 7 months after the last dose. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for at least 4 months after receiving the last dose of TALZENNA [see Warnings and Precautions (5.3), Use in Specific Populations (8.1, 8.3)].
  • Lactation: Advise patients not to breastfeed while taking TALZENNA and for at least 1 month after receiving the last dose [see Use in Specific Populations (8.2)].

This product’s label may have been updated. For current full prescribing information, please visit www.talzenna.com.

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LAB-1271-3.0

This Patient Information has been approved by the U.S. Food and Drug Administration.Issued 3/2020
PATIENT INFORMATIONTALZENNA® (Tal-ZEN-ah)(talazoparib)capsules
What is the most important information I should know about TALZENNA?TALZENNA may cause serious side effects, including: Bone marrow problems called Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). Some people who have cancer and who have received previous treatment with chemotherapy or certain other medicines for their cancer have developed MDS or AML during or after treatment with TALZENNA. MDS or AML may lead to death. If you develop MDS or AML, your healthcare provider will stop treatment with TALZENNA.Symptoms of low blood cell counts are common during treatment with TALZENNA, but can be a sign of serious problems, including MDS or AML. Tell your healthcare provider if you have any of the following symptoms during treatment with TALZENNA:
  • weakness
  • weight loss
  • fever
  • frequent infections
  • blood in urine or stool
  • shortness of breath
  • feeling very tired
  • bruising or bleeding more easily
Your healthcare provider will do blood tests to check your blood cell counts:
  • before treatment with TALZENNA
  • every month during treatment with TALZENNA
  • weekly if you have low blood cell counts that last a long time. Your healthcare provider may stop treatment with TALZENNA until your blood cell counts improve.
See “What are the possible side effects of TALZENNA?” below for other side effects of TALZENNA.
What is TALZENNA? TALZENNA is a prescription medicine used to treat adults with:
  • a certain type of breast cancer (human epidermal growth factor receptor 2 [HER2]-negative), and
  • an abnormal inherited BRCA gene, and
  • whose cancer has spread to other parts of the body (locally advanced or metastatic).
Your healthcare provider will perform a test to make sure that TALZENNA is right for you.It is not known if TALZENNA is safe and effective in children.
Before taking TALZENNA, tell your healthcare provider about all of your medical conditions, including if you:
  • have kidney problems
  • are pregnant or plan to become pregnant. TALZENNA can harm your unborn baby, and may cause loss of pregnancy (miscarriage). You should not become pregnant during treatment with TALZENNA. Tell your healthcare provider right away if you are pregnant or become pregnant during treatment with TALZENNA.
    • If you are able to become pregnant, your healthcare provider may do a pregnancy test before you start treatment with TALZENNA.
    • Females who are able to become pregnant should use effective birth control (contraception) during treatment with TALZENNA and for at least 7 months after receiving the last dose of TALZENNA. Talk to your healthcare provider about forms of birth control that may be right for you.
    • Males with female partners who are pregnant or are able to become pregnant should use effective birth control during treatment with TALZENNA and for at least 4 months after receiving the last dose of TALZENNA.
  • are breastfeeding or plan to breastfeed. It is not known if TALZENNA passes into your breast milk. Do not breastfeed during treatment with TALZENNA and for at least 1 month after receiving the last dose of TALZENNA. Talk to your healthcare provider about the best way to feed your baby during this time.
Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. Taking TALZENNA and certain other medicines can affect how TALZENNA works and may cause side effects.Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take TALZENNA?
  • Take TALZENNA exactly as your healthcare provider tells you.
  • Do not change your dose or stop taking TALZENNA without first talking with your healthcare provider.
  • Take TALZENNA 1 time a day.
  • Take TALZENNA with or without food.
  • Swallow TALZENNA capsules whole. Do not dissolve or open TALZENNA capsules.
  • Your healthcare provider may change your dose of TALZENNA or tell you to stop taking TALZENNA depending on how you respond to treatment.
  • If you miss a dose of TALZENNA or vomit, take your next dose at your regular time. Do not take an extra dose to make up for a missed dose.
  • If you take too much TALZENNA, call your healthcare provider or go to the nearest hospital emergency room right away.
What are the possible side effects of TALZENNA?TALZENNA may cause serious side effects, including: See “What is the most important information I should know about TALZENNA?“The most common side effects of TALZENNA include:
  • tiredness or weakness
  • low number of red or white blood cells
  • nausea
  • low number of platelets
  • headache
  • loss of appetite
  • diarrhea
  • vomiting
  • hair loss
TALZENNA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of TALZENNA.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store TALZENNA? Store TALZENNA at 68°F to 77°F (20°C to 25°C ).Keep TALZENNA and all medicines out of the reach of children.
General information about the safe and effective use of TALZENNA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TALZENNA for a condition for which it is not prescribed. Do not give TALZENNA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about TALZENNA that is written for health professionals.
What are the ingredients in TALZENNA?Active ingredient: talazoparib tosylateInactive ingredients: silicified microcrystalline cellulose (sMCC). The white and ivory and white and light red opaque capsule shells contain hypromellose (HPMC), yellow iron oxide, red iron oxide and titanium dioxide. The printing ink contains shellac, black iron oxide, potassium hydroxide, ammonium hydroxide, and propylene glycol.

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