ALECENSA® (alectinib) Was Studied in Multiple Clinical Trials

Study NP28761—North American Trial Design2,4

ALECENSA® (alectinib) Study NP28761 North American Clinical Trial Design

 

  • Single-arm, North American, multicenter study2
  • Median duration of follow up: 4.8 months (IRC, INV)2
  • Patients may have received prior chemotherapy2

 

Study—NP28673 International Trial Design2,4

ALECENSA® (alectinib) Study NP28673 International Clinical Trial Design

 

  • Single-arm, international, multicenter study2
  • Median duration of follow-up: 10.9 months (IRC); 7.0 months (INV)2
  • Patients may have received prior chemotherapy2

 

Patients in both studies were required to have documented ALK+ NSCLC based on an FDA-approved test and ECOG PS of 0-2.2

aAssessed according to RECIST v1.1.2

Patient Characteristics in Two Phase 2 Clinical Trials

Baseline Characteristics2,4

Baseline Characteristics of the North American and International Studies

ALECENSA Demonstrated Meaningful and Durable Objective Responses

ORR in the North American and International Studies2

Objective Response Rates with ALECENSA® (alectinib) in North American & International Studies

 

  • The major efficacy outcome measure in both studies was ORR according to RECIST v1.1 as evaluated per IRC2
  • 18 patients in the North American study and 16 patients in the International study did not have measurable disease at baseline per IRC assessment and were classified as non-responders in the IRC analysis2
  • All responses were partial responses2

 

Median DOR2

Median Duration of Response of ALECENSA® (alectinib) in the North American & International Studies
  • The median duration of follow-up for the North American study was 4.8 months for both IRC and Investigator assessments and for the International study, 10.9 months for IRC assessment and 7.0 months for Investigator assessment2

ALECENSA Delivered Robust and Sustained CNS Responses

CNS ORR in Patients With Measurable Lesions2 | IRC 

CNS Objective Response Rate with ALECENSA® (alectinib) in North American & International Studies

 

  • The ORR in CNS metastases in the subgroup of 51 patients with measurable lesions in the CNS at baseline was assessed by IRC and determined by RECIST v1.1 in both studies2
  • 35 (69%) patients with measurable CNS lesions received prior brain radiation, including 25 (49%) who completed radiation treatment at least 6 months before starting treatment with ALECENSA2

 

CNS responses were observed irrespective of prior brain radiation status.2

Median CNS DOR in the North American & International Studies2 | IRC

Median CNS Duration of Response of ALECENSA® (alectinib) in the North American & International Studies
  • The DOR in CNS metastases in the subgroup of 51 patients with measurable lesions in the CNS at baseline was assessed by IRC and determined by RECIST v1.1 in both studies2

Adverse Reactions Post-Crizotinib Treatment

Adverse reactions from clinical trial experience2

 

  • Serious adverse reactions occurred in 19% of patients, and the most frequently reported serious adverse reactions were pulmonary embolism (1.2%), dyspnea (1.2%), and hyperbilirubinemia (1.2%)2
  • Fatal adverse reactions occurred in 2.8% of patients, and included hemorrhage (0.8%), intestinal perforation (0.4%), dyspnea (0.4%), pulmonary embolism (0.4%), and endocarditis (0.4%)2

 

Adverse Reactions in ≥10% (All Grades) or ≥2% (Grade 3-4) of Patients in the North American & International Studies2

Adverse Reactions of Patients Post-Crizotinib Treatment in the North American & International Studies

bPer CTCAE version 4.0.
cIncludes fatigue and asthenia.
dIncludes peripheral edema, edema, generalized edema, eyelid edema, and periorbital edema.
eIncludes myalgia and musculoskeletal pain.
fIncludes rash, maculopapular rash, acneiform dermatitis, erythema, generalized rash, papular rash, pruritic rash, and macular rash.
gIncludes 1 Grade 5 event.
hIncludes blurred vision, vitreous floaters, visual impairment, reduced visual acuity, asthenopia, and diplopia. 

Incidence of photosensitivity in clinical trials2

  • Photosensitivity occurred in 9.9% of patients exposed to ALECENSA in both studies
  • Patients were advised to avoid sun exposure and to use broad-spectrum sunscreen
  • The incidence of Grade 2 photosensitivity was 0.4% and the remaining events were Grade 1 in severity

23% of patients initiating treatment at the recommended dose required at least 1 dose reduction2

6% of patients treated with ALECENSA in clinical trials permanently discontinued treatment due to adverse reactions2

Dose modifications due to adverse reactions in clinical trials2

  • The most frequent adverse reactions that led to permanent discontinuation were hyperbilirubinemia (1.6%), increased ALT levels (1.6%), and increased AST levels (1.2%)
  • The most frequent adverse reactions that led to dose reductions or interruptions were elevations in bilirubin (6%), CPK (4.3%), ALT (4%), AST (2.8%), and vomiting (2.8%)
  • The median time to first dose reduction was 48 days

Laboratory Abnormalities Occurring in >20% of Patients in Both Studies2

Laboratory Abnormalities Occurring in of Patients Post-Crizotinib Treatment in Both Studies

iPer CTCAE version 4.0.
jn=218 for CPK (with baseline values missing for 91 of these patients).
kn=152 for fasting blood glucose (with baseline values missing for 5 of these patients).
lOnly patients with creatinine increases based on ULN definition.
mn=217 for lymphocytes (with baseline values missing for 5 of these patients).

1L=first-line; ALT=alanine transaminase; AST=aspartate transaminase; CI=confidence interval; CNS=central nervous system; CPK=creatine phosphokinase; CR=complete response; CTCAE=common terminology criteria for adverse events; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; INV=Investigator; IRC=Independent Review Committee; NE=not estimable; ORR=objective response rate; PFS=progression-free survival; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; ULN=upper limit of normal.

1L PFS Results icon

1L PFS Results

View PFS results vs crizotinib from the head-to-head ALEX trial.

CNS protection icon

CNS Efficacy in 1L ALK+ mNSCLC

Learn more about CNS efficacy with ALECENSA.

Resources icon

Financial Support for Patients

Learn more about ALECENSA patient financial and practice resources.

Indication

ALECENSA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (mNSCLC) as detected by an FDA-approved test.

Warnings and Precautions

Hepatotoxicity

  • Of 405 patients, elevations of AST >5X the upper limit of normal (ULN) occurred in 4.6% of patients, and elevations of ALT >5X the ULN occurred in 5.3% of patients. Elevations of bilirubin >3X the ULN occurred in 3.7% of patients. The majority (69% of the patients with hepatic transaminase elevations and 68% of the patients with bilirubin elevations) of these events occurred during the first 3 months of treatment. Six patients discontinued ALECENSA for Grades 3-4 AST and/or ALT elevations, and 4 patients discontinued ALECENSA for Grade 3 bilirubin elevations. Concurrent elevations in ALT or AST ≥3X the ULN and total bilirubin ≥2X the ULN, with normal alkaline phosphatase, occurred in <1% of patients treated with ALECENSA across clinical trials. Three patients with Grades 3-4 AST/ALT elevations had drug-induced liver injury (2 documented by liver biopsy)
  • Monitor liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 3 months of treatment, then once a month and as clinically indicated, with more frequent testing in patients who develop transaminase and bilirubin elevations. Based on the severity of the adverse drug reaction, withhold ALECENSA and resume at a reduced dose, or permanently discontinue ALECENSA

Interstitial Lung Disease (ILD)/Pneumonitis

  • ILD/pneumonitis occurred in 3 (0.7%) patients treated with ALECENSA. One (0.2%) of these events was severe (Grade 3)
  • Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, and fever)
  • Immediately withhold ALECENSA treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue ALECENSA if no other potential causes of ILD/pneumonitis have been identified

Renal Impairment

  • Renal impairment occurred in 8% of patients. The incidence of Grade ≥3 renal impairment was 1.7%, of which 0.5% were fatal events
  • Dose modifications for renal impairment were required in 3.2% of patients. Median time to Grade ≥3 renal impairment was 3.7 months (range 0.5 to 14.7 months)
  • Permanently discontinue ALECENSA for Grade 4 renal toxicity. Withhold ALECENSA for Grade 3 renal toxicity until recovery to ≤1.5X ULN, then resume at reduced dose

Bradycardia

  • Symptomatic bradycardia can occur with ALECENSA. Cases of bradycardia (8.6%) have been reported in patients treated with ALECENSA. Eighteen percent of 365 patients treated with ALECENSA for whom serial ECGs were available had heart rates of <50 beats per minute (bpm)
  • Monitor heart rate and blood pressure regularly. Dose modification is not required in cases of asymptomatic bradycardia. In cases of symptomatic bradycardia that are not life-threatening, withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm and evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If attributable to a concomitant medication, resume ALECENSA at a reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence. Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified

Severe Myalgia and Creatine Phosphokinase (CPK) Elevation

  • Myalgia or musculoskeletal pain occurred in 26% of patients. The incidence of Grade 3 myalgia/musculoskeletal pain was 0.7%. Dose modifications for myalgia/musculoskeletal pain were required in 0.5% of patients
  • Elevations of CPK occurred in 41% of 347 patients with CPK laboratory data. The incidence of Grade 3 elevations of CPK was 4.0%. Median time to Grade 3 CPK elevation was 14 days (interquartile range 13-28 days). Dose modifications for elevation of CPK occurred in 3.2% of patients
  • Advise patients to report any unexplained muscle pain, tenderness, or weakness. Assess CPK levels every 2 weeks for the first month of treatment and as clinically indicated in patients reporting symptoms. Based on the severity of the CPK elevation, withhold ALECENSA, then resume or reduce dose

Hemolytic Anemia

  • Hemolytic anemia has been reported with ALECENSA, including cases associated with a negative direct antiglobulin test (DAT) result. If hemolytic anemia is suspected, withhold ALECENSA and initiate appropriate laboratory testing. If hemolytic anemia is confirmed, consider resuming at a reduced dose upon resolution or permanently discontinue

Embryo-Fetal Toxicity

  • Based on findings from animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to pregnant women. Administration of ALECENSA to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7X those observed in humans with ALECENSA 600 mg twice daily. Advise pregnant women of the potential risk to a fetus
  • Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week following the final dose

Most Common Adverse Reactions

  • The most common adverse reactions (incidence ≥20%) were constipation (34%), fatigue (26%), edema (22%), myalgia (23%), and anemia (20%)

Use in Specific Populations

Pregnancy

  • Based on animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to a pregnant woman. There are no available data on ALECENSA use in pregnant women
  • In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively

Lactation

  • Because of the potential for serious adverse reactions in breastfed infants from ALECENSA, advise a lactating woman not to breastfeed during treatment with ALECENSA and for 1 week after final dose

Females and Males of Reproductive Potential

  • ALECENSA can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week after the final dose
  • Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months following the final dose

Hepatic Impairment

  • Increased exposure of alectinib occurred in patients with severe hepatic impairment (Child-Pugh C). The recommended dose of ALECENSA in patients with severe hepatic impairment (Child-Pugh C) is 450 mg orally twice daily

Patient Counseling Information

Photosensitivity

  • Inform patients of the signs and symptoms of photosensitivity. Advise patients to avoid prolonged sun exposure while taking ALECENSA and for at least 7 days after discontinuation and to use proper protection from the sun. Advise patients to use a broad spectrum ultraviolet A (UVA)/ultraviolet B (UVB) sunscreen and lip balm (SPF ≥50) to help protect against potential sunburn

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see additional Important Safety Information in full Prescribing Information.

    • SHS US Claims, July 2019-June 2020; IQVIA US Claims, July 2020-March 2021.

      SHS US Claims, July 2019-June 2020; IQVIA US Claims, July 2020-March 2021.

    • ALECENSA [prescribing information]. South San Francisco, CA: Genentech USA, Inc; 2021.

      ALECENSA [prescribing information]. South San Francisco, CA: Genentech USA, Inc; 2021.

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      Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non–small cell lung cancer. N Engl J Med. 2017;377:829-838.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed May 26, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed May 26, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 

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