tnAcity Data Presented at SABCS Evaluates the Investigational Use of ABRAXANE® as First-Line Treatment of Metastatic Triple Negative Breast Cancer

Phase II tnAcity Trial found a significantly longer Progression Free Survival with ABRAXANE + carboplatin compared to ABRAXANE + gemcitabine or carboplatin + gemcitabine regimens

SUMMIT, N.J.--()--Celgene Corporation (NASDAQ:CELG) today announced that the results of its randomized phase II tnAcity trial of ABRAXANE® for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) December 6-10, 2016. The trial found that an investigational weekly combination regimen of ABRAXANE + carboplatin had significantly longer progression-free survival (PFS) (7.4 months) compared to weekly regimens of either ABRAXANE + gemcitabine (5.4 months) or of carboplatin + gemcitabine (6.0 months) as first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC).i

The phase II trial randomized 191 women with mTNBC to receive one of three weekly regimens (dosed 2 out of 3 weeks): ABRAXANE + carboplatin, ABRAXANE + gemcitabine, or carboplatin + gemcitabine as first-line treatment. The study findings demonstrated that ABRAXANE + carboplatin resulted in significantly longer PFS (7.4 months) than combination regimens with ABRAXANE + gemcitabine (5.4 months; P=0.02, HR 0.60 (95% CI, 0.39-0.93)) or carboplatin + gemcitabine (6.0 months; P= 0.03, HR 0.61 (95% CI, 0.39-0.94)). tnAcity also found that those treated with the ABRAXANE + carboplatin regimen experienced a longer median treatment duration (25 weeks) than those treated with ABRAXANE + gemcitabine (18.1 weeks) or carboplatin + gemcitabine (20.1 weeks).i

The most common grade ≥3 treatment emergent adverse events (TEAEs) observed in the ABRAXANE + carboplatin, ABRAXANE + gemcitabine, and carboplatin + gemcitabine arms, respectively, during the study were mainly hematologic and included neutropenia (42%, 27%, 52%), anemia (13%, 12%, 27%), thrombocytopenia (9%, 7%, 28%), leukopenia (6%, 3%, 11%), febrile neutropenia (5%, 2%, 0%), peripheral neuropathy (5%, 7%, 2%) and fatigue (3%, 15%, 3%). A median of 8 treatment cycles were initiated for the ABRAXANE + carboplatin arm and 6 cycles for both the ABRAXANE + gemcitabine and carboplatin + gemcitabine arms. The percentage of patients that discontinued any study drug due to a TEAE was 45% for ABRAXANE + carboplatin and 25% for each of the other arms. The most common AEs leading to discontinuation of any study drug included thrombocytopenia, anemia, neutropenia and drug hypersensitivity.i

“Metastatic triple negative breast cancer is one of the most challenging types of cancers for treating physicians and patients alike, and there remains an important unmet need in these patients to find more effective treatment options,” said Dr. Denise A. Yardley, Senior Investigator, Breast Cancer Research Program; Principal Investigator, Sarah Canon Research Institute. “These data add to the body of knowledge about ABRAXANE in metastatic triple negative breast cancer, a disease that requires additional research.”

After taking into consideration the rapidly changing breast cancer treatment landscape, which has a significant focus on immuno-oncology treatments, Celgene had determined not to move forward with the phase III portion of tnAcity. The Company will instead focus its breast cancer research support on ABRAXANE/Immunotherapy combinations and remains committed to applying the findings of tnAcity to ongoing and future research of ABRAXANE in breast cancer for patients with high unmet needs.

“The findings of tnAcity are encouraging, illustrating that an ABRAXANE-containing regimen may have activity in a type of breast cancer with few viable treatments and these findings give researchers additional insight into how to treat metastatic triple negative breast cancer,” said Michael Pehl, President, Hematology and Oncology for Celgene. “Celgene is committed to continuing to support research in breast cancer to identify regimens for patients with aggressive disease and in areas with limited treatment options.”

ABRAXANE is not indicated for the first-line treatment of metastatic breast cancer, or for the treatment regimens studied in tnAcity.

ABOUT tnAcityi,ii

tnAcity is a phase II/III multicenter, open-label, randomized clinical trial conducted in 139 centers in 12 countries. The study evaluated the safety and efficacy of the investigational use of a weekly treatment regimen of ABRAXANE in combination with carboplatin or gemcitabine as a first-line treatment of women with metastatic triple negative breast cancer (mTNBC) compared to a gemcitabine + carboplatin regimen.ii

The phase II portion of the tnAcity trial evaluated 191 patients with metastatic triple negative breast cancer (mTNBC) who had received no prior systemic chemotherapy treatment for their mTNBC and had an ECOG performance status of 0 or 1. Patients were randomized to one of three treatment arms: ABRAXANE 125 mg/m2 + carboplatin AUC 2, ABRAXANE 125 mg/m2 + gemcitabine 1000 mg/m2, or carboplatin AUC 2 + gemcitabine 1000 mg/m2 dosed weekly on days 1 and 8 of a 21-day cycle. The median age in each treatment arm was 55 (ABRAXANE + carboplatin), 53 (ABRAXANE + gemcitabine) and 59 (carboplatin + gemcitabine) years. The primary endpoint of the phase II trial was investigator assessed progression free survival (PFS). Secondary endpoints evaluated in the study included overall survival (OS) and objective response rate (ORR).

Additional ABRAXANE Data Presented at SABCS

Additional investigator initiated studies presented at SABCS also evaluated the investigational uses of ABRAXANE in the neoadjuvant setting in patients with previously untreated breast cancer (GeparSepto; P5-16-03) and as induction and maintenance therapy for women with HER2-negative metastatic breast cancer (SNAP; P5-15-05).

ABOUT ABRAXANE

ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

Important Safety Information

WARNING – NEUTROPENIA

  • Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
  • Note: An albumin form of paclitaxel may substantially affect a drug's functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS

CONTRADINDICATIONS

Neutrophil Counts

  • ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500 cells/mm3

Hypersensitivity

  • Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug

WARNINGS AND PRECAUTIONS

Hematologic Effects

  • Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC)
  • Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1
  • Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm3
  • In the case of severe neutropenia ( < 500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with MBC
  • Resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level > 1500 cells/mm3 and platelets recover to > 100,000 cells/mm3

Nervous System

  • Sensory neuropathy is dose- and schedule-dependent
  • The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
  • If ≥ Grade 3 sensory neuropathy develops, withhold until resolution to Grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE

Hypersensitivity

  • Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
  • Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug

Hepatic Impairment

  • Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
  • Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
  • For MBC, the starting dose should be reduced for patients with moderate or severe hepatic impairment

Albumin (Human)

  • ABRAXANE contains albumin (human), a derivative of human blood

Use in Pregnancy: Pregnancy Category D

  • ABRAXANE can cause fetal harm when administered to a pregnant woman
  • If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
  • Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE

Use in Men

  • Men should be advised not to father a child while receiving ABRAXANE

ADVERSE REACTIONS

Randomized Metastatic Breast Cancer (MBC) Study

  • The most common adverse reactions (≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%, 82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%, 31%), anemia (any 33%, 25%; severe 1%, <1%), nausea (any 30%, 22%; severe 3%, <1%), diarrhea (any 27%, 15%; severe <1%, 1%) and infections (24%, 20%), respectively
  • Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients
  • Other adverse reactions of note with the use of ABRAXANE vs paclitaxel injection included vomiting (any 18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%, <1%), mucositis (any 7%, 6%; severe <1%, 0%), hepatic dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%, 3%; severe <1%, <1%), neutropenic sepsis (<1%, <1%), and injection site reactions (<1%, 1%), respectively. Dehydration and pyrexia were also reported
  • Renal dysfunction (any 11%, severe 1%) was reported in patients treated with ABRAXANE (n=229)
  • In all ABRAXANE-treated patients (n=366), ocular/visual disturbances were reported (any 13%; severe 1%)
  • Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension
  • Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported

Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

  • Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or to human albumin has not been studied
  • There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
  • There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration

DRUG INTERACTIONS

  • Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4

USE IN SPECIFIC POPULATIONS

Nursing Mothers

  • It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

Pediatric

  • The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated

Geriatric

  • A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and peripheral edema was found in patients 65 years or older who received ABRAXANE for MBC in a pooled analysis of clinical studies

Renal Impairment

  • There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)

DOSAGE AND ADMINISTRATION

  • Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
  • Reduce starting dose in MBC patients with moderate to severe hepatic impairment
  • Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity
  • Monitor patients closely

Please see full Prescribing Information, including Boxed WARNING.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, FaceBook and YouTube.

Forward-Looking Statements

This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.

i Yardley D, et al. nab-Paclitaxel + Carboplatin or Gemcitabine vs Gemcitabine + Carboplatin as First-Line Treatment for Patients With Triple-Negative Metastatic Breast Cancer: Results From the Randomized Phase II Portion of the tnAcity Trial. Poster 874. Presented at the 2016 San Antonio Breast Cancer Symposium (SABCS), December 6-10, 2016.

ii Clinicaltrials.gov. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer) (tnAcity). Available at: https://www.clinicaltrials.gov/ct2/show/NCT01881230?term=tnacity&rank=1. Accessed November 29, 2016.

Contacts

Celgene Corporation
Investors:
908-673-9628
investors@celgene.com
or
Media:
908-673-2275
media@celgene.com

Release Summary

Celgene presented at SABCS findings of tnAcity, which found a first-line weekly combo regimen of ABRAXANE/carboplatin had longer PFS vs ABRAXANE/gemcitabine or carboplatin/gemcitabine in mTNBC patient

Contacts

Celgene Corporation
Investors:
908-673-9628
investors@celgene.com
or
Media:
908-673-2275
media@celgene.com