BOTHELL, Wash.--(BUSINESS WIRE)-- Seattle Genetics, Inc.. today announced positive results from exploratory analyses of intracranial efficacy, including survival, in patients with HER2-positive metastatic breast cancer (MBC) who had stable or active brain metastases in the HER2CLIMB pivotal trial of TUKYSA (tucatinib). HER2CLIMB compared TUKYSA in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with unresectable, locally advanced or metastatic HER2-positive breast cancer with or without brain metastases. Of the patients enrolled in the trial, 48 percent had a presence or history of brain metastases. Results demonstrated that the addition of TUKYSA to trastuzumab and capecitabine in patients with brain metastases delayed progression in the brain, doubled the intracranial response rate (tumor shrinkage in the brain) and reduced the overall risk of death by nearly half. The data were consistent across patients who had either stable or active brain metastases. Results were presented in an oral presentation in the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200529005149/en/
(Photo: Business Wire)
TUKYSA in combination with trastuzumab and capecitabine was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. Primary results from HER2CLIMB were first presented at the San Antonio Breast Cancer Symposium in December 2019 and published in the New England Journal of Medicine.
It is immensely gratifying to see for the first time, results for patients with stable or active brain metastases who are not typically included in clinical trials, especially when you consider that nearly half of patients with HER2-positive metastatic breast cancer experience disease progression to the brain, said Nancy U. Lin, M.D., director of the Metastatic Breast Cancer Program in the Susan F. Smith Center for Womens Cancers at Dana-Farber in Boston, MA. These additional analyses provide further evidence that TUKYSA improves survival and delays cancer progression in the brain for patients with HER2-positive metastatic breast cancer who have brain metastases.
These additional analyses, together with the primary analysis of HER2CLIMB, show TUKYSA is active for patients with and without disease that has spread to the brain, said Roger Dansey, M.D., Chief Medical Officer of Seattle Genetics. We continue to be encouraged by the remarkable clinical activity of TUKYSA in combination with trastuzumab and capecitabine and look forward to evaluating its potential in additional treatment settings and tumor types through our ongoing clinical program.
The new data that further examine TUKYSAs effect in the brain include exploratory analyses for central nervous system progression-free survival (CNS-PFS), overall survival (OS), intracranial objective response rate (ORR-IC) and duration of response in HER2-positive metastatic breast cancer patients whose disease had spread to the brain.
The exploratory analyses demonstrated that patients with brain metastases who received the TUKYSA combination versus trastuzumab and capecitabine alone had:
Endpoint
TUKYSA Arm (TUKYSA + trastuzumab + capecitabine)
Control Arm (Placebo + trastuzumab + capecitabine)
OS Benefit in All Patients with Brain Metastases
N=198
N=93
Risk Reduction
42% (Hazard Ratio [HR]=0.58 [95% Confidence Interval (CI): 0.40, 0.85]; p=0.005)
One-Year OS
70.1% (95% CI: 62.1, 76.7)
46.7% (95% CI: 33.9, 58.4)
Median OS
18.1 months (95% CI: 15.5, not estimable)
12 months (95% CI: 11.2, 15.2)
CNS-PFS Benefit in All Patients with Brain Metastases
N=198
N=93
Risk Reduction
68% (HR=0.32 [95% CI: 0.22, 0.48]; p<0.0001)
One-year CNS-PFS
40.2% (95% CI: 29.5, 50.6)
0%
Median CNS-PFS
9.9 months (95% CI: 8.0, 13.9)
4.2 months (95% CI: 3.6, 5.7)
Intracranial Objective Response Rate (ORR-IC) in Patients with Active Brain Metastases and Measurable Intracranial Lesions at Baseline
N=55
N=20
Complete Response (CR)
3 (5.5%)
1 (5.0%)
Partial Response (PR)
23 (41.8%)
3 (15.0%)
Stable Disease
24 (43.6%)
16 (80.0%)
Progressive Disease
2 (3.6%)
0
Not Available
3 (5.5%)
0
ORR-IC (CR+PR)
26 (47%) (95% CI: 34, 61)
4 (20%) (95% CI: 6, 44)
Duration of Response-IC
6.8 months (95% CI: 5.5, 16.4)
3 months (95% CI: 3.0, 10.3)
About HER2CLIMB
HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing TUKYSA in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including OS, PFS per BICR in patients with brain metastases at baseline and confirmed ORR.1
Results of Primary Analysis of HER2CLIMB
Control Arm (Placebo + trastuzumab + capecitabine)
PFS by BICR in the first 480 patients
46% reduction in risk of progression or death (HR=0.54 [95% CI: 0.42, 0.71]; p<0.00001; N=480)
OS
34% reduction in risk of death (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048; N=612)
PFS* by BICR in patients with brain metastases
52% reduction in risk of progression or death (HR=0.48 [95% CI: 0.34, 0.69]; p<.0.00001; N=291)
One-Year PFS
25% (95% CI: 17, 34)
0%
Median PFS
7.6 months (95% CI: 6.2, 9.5)
5.4 months (95% CI: 4.1, 5.7)
*standard RECIST, includes brain and body
In HER2CLIMB, serious adverse reactions occurred in 26 percent of patients who received TUKYSA. Serious adverse reactions occurring in 2 percent or more of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea, abdominal pain, and seizure (2% each). The most common adverse reactions occurring in 20 percent or more of patients who received TUKYSA were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Adverse reactions leading to treatment discontinuation occurred in 6 percent of patients who received TUKYSA; adverse reactions leading to treatment discontinuation of TUKYSA (in 1 percent or more of patients) were hepatotoxicity (1.5%) and diarrhea (1%).1
About HER2-Positive Breast Cancer
Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. An estimated 279,100 new cases of breast cancer will be diagnosed in the U.S. in 2020.2 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.3,4,5 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time. 6,7,8
About TUKYSA (tucatinib)
TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,9 In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.1
Important Safety Information
Warnings and Precautions
If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
Adverse Reactions
Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.
Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in 1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in 2% of patients were hepatotoxicity (8%) and diarrhea (6%).
The most common adverse reactions in patients who received TUKYSA (20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.
Lab Abnormalities
In HER2CLIMB, Grade 3 laboratory abnormalities reported in 5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.
Drug Interactions
Use in Specific Populations
For more information, please see the full Prescribing Information for TUKYSA here.
About Seattle Genetics
Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in peoples lives. The company is headquartered in the Seattle, Washington area, and has offices in California, Switzerland and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
Forward Looking Statements
Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of TUKYSA including its efficacy, safety and therapeutic uses, including its use in combination with trastuzumab and capecitabine to treat patients with HER2-positive metastatic breast cancer with brain metastases who have received one or more previous anti-HER2 therapies, and its potential use in additional treatment settings and tumor types. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the difficulty and uncertainty of pharmaceutical product development; the possibility that adverse events or safety signals may occur; that utilization and adoption of TUKYSA by prescribing physicians may be limited due to impacts related to the COVID-19 pandemic, availability and extent of reimbursement or other factors; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended March 31, 2020 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Here is the original post:
Seattle Genetics Announces Positive Results from Exploratory Analyses of HER2CLIMB for TUKYSA (tucatinib) in Brain Metastases Patients With...
- Hyperbaric Chamber Therapy Brain Injury - May 7th, 2011 [May 7th, 2011]
- Treatment for Traumatic Brain Injury - May 9th, 2011 [May 9th, 2011]
- Atlanta Traumatic Brain Injury Treatment Emory - May 11th, 2011 [May 11th, 2011]
- Hyperbaric Oxygen Therapy Brain Injury Part 2 (Tbi) - May 20th, 2011 [May 20th, 2011]
- Mark, anoxi brain injury, physical therapy after stem cell treatment - May 21st, 2011 [May 21st, 2011]
- Hyperbaric Oxygen Therapy - May 21st, 2011 [May 21st, 2011]
- Bob Hahn Traumatic Brain Injury Recovery - May 23rd, 2011 [May 23rd, 2011]
- Mark, anoxi brain injury, after stem cell treatment at Tiantan Puhua Hospital Beijing - May 24th, 2011 [May 24th, 2011]
- New Beginnings community center for brain injury rehabilitation - May 30th, 2011 [May 30th, 2011]
- Traumatic Brain Injury - Part 1 - Dr. Robert Kohn, Neurologist - June 2nd, 2011 [June 2nd, 2011]
- Am I Brain Damaged? from traumatic brain injury - June 3rd, 2011 [June 3rd, 2011]
- SLI Wellness Center for Brain Injury Rehabilitation - June 11th, 2011 [June 11th, 2011]
- Update on Libya, Radiation in Japan, Tramatic Brain Injury treatment and more, 03/23/2011 - June 12th, 2011 [June 12th, 2011]
- Origami Brain Injury Rehabilitation Center - Finding Your Path - June 12th, 2011 [June 12th, 2011]
- Traumatic Brain Injury - Part 5 - Doctor Kohn, Chicago Neurologist - June 16th, 2011 [June 16th, 2011]
- The struggle to treat traumatic brain injury - June 17th, 2011 [June 17th, 2011]
- Traumatic Brain Injury Survivor Speaks about ProTECT trial at UC Health University Hospital - June 17th, 2011 [June 17th, 2011]
- Stem cell treatment for Brain Injury of Adrian - June 23rd, 2011 [June 23rd, 2011]
- Division of Vocational Rehabilitation Services for Traumatic Brain Injury (TBI) - June 24th, 2011 [June 24th, 2011]
- Hyperbaric Chamber Treatment Stroke and Traumatic Brain Injury TBI - July 4th, 2011 [July 4th, 2011]
- Traumatic Brain Injury - Part 2 - Dr. Robert Kohn, Neurologist - July 6th, 2011 [July 6th, 2011]
- Traumatic Brain Injury - Part 7 - Doctor Kohn, MD, Neurology, Neuropsychiatry - July 14th, 2011 [July 14th, 2011]
- Neurofeedback Training and Treatment at Healing Unleashed in Denver Colorado - July 15th, 2011 [July 15th, 2011]
- Alexis Verzal takes independent steps - July 18th, 2011 [July 18th, 2011]
- The New WalkAide System: Advanced Functional Electrical Stimulation (FES) for Treatment of Foot Drop - July 18th, 2011 [July 18th, 2011]
- Doctors Cool Newborn to Limit Brain Damage - July 19th, 2011 [July 19th, 2011]
- Traumatic Brain Injury - Part 6 - by Neurologist, Dr. Robert Kohn - July 24th, 2011 [July 24th, 2011]
- Brain injury and trauma treatment by homeopathy - July 31st, 2011 [July 31st, 2011]
- Traumatic Brain Injury - Part 4 - Dr. Kohn, Neuropsychiatrist / Neurologist - August 9th, 2011 [August 9th, 2011]
- Preserving Hope, Predicting Health - August 17th, 2011 [August 17th, 2011]
- Sask Brain Injury Association - August 19th, 2011 [August 19th, 2011]
- Cognition and Mild Head Injury by Dr. Muriel Lezak - August 21st, 2011 [August 21st, 2011]
- Brain injury_Shawna_ USA_before stem cell treatment 1.wmv - August 25th, 2011 [August 25th, 2011]
- Origami Brain Injury Rehabilitation Center - Recovery is a Journey - August 26th, 2011 [August 26th, 2011]
- Different types of Concussions by Dr. James Chesnutt.mov - August 30th, 2011 [August 30th, 2011]
- Brain injury_Shawna_ USA_after stem cell treatment 1.wmv - September 11th, 2011 [September 11th, 2011]
- With Brain Injuries, Soldiers Face A Battle For Care - September 23rd, 2011 [September 23rd, 2011]
- Tripler Medical Center Treats Traumatic Brain Injury (TBI) - September 24th, 2011 [September 24th, 2011]
- Sessions' Traumatic Brain Injury Amendment to DOD Appropriations - October 2nd, 2011 [October 2nd, 2011]
- Using Stem Cells for Treatment of TBI | Dr. Charles Cox | Research Trials - October 5th, 2011 [October 5th, 2011]
- Healing brain injuries - October 8th, 2011 [October 8th, 2011]
- Veterans Services at Origami Brain Injury Rehabilitation Center - - October 8th, 2011 [October 8th, 2011]
- Hope Beyond Trauma - October 9th, 2011 [October 9th, 2011]
- Traumatic Brain Injury - Part 3 - by Neurologist Dr. Robert Kohn - October 10th, 2011 [October 10th, 2011]
- Understanding and Improving Vocational Outcomes following Traumatic Brain Injury - Video - October 16th, 2011 [October 16th, 2011]
- LI facility dedicated to Terri Schiavo - Video - October 17th, 2011 [October 17th, 2011]
- Treating Traumatic Brain Injury with Neurotopia - featuring Holden McCray - October 18th, 2011 [October 18th, 2011]
- Brain Injury Survivors: Adriana Villar (Making a Difference: Story 1) - Video - October 21st, 2011 [October 21st, 2011]
- Fabio - brain injury - Video - October 23rd, 2011 [October 23rd, 2011]
- The Latest Developments in Traumatic Brain Injury Treatment - Video - October 25th, 2011 [October 25th, 2011]
- Stem Cell Treatments and Brain Damage Video of MRI of Brain Chambers WWW.STEMCELLREGENMED.COM - Video - October 29th, 2011 [October 29th, 2011]
- Military lags on promising treatment for brain-injured soldiers - Video - November 6th, 2011 [November 6th, 2011]
- Brian Moylan (TBI survivor) talking on treatment from the NHS - Video - November 10th, 2011 [November 10th, 2011]
- Brain Injury Experts at Madonna Rehabilitation Hospital - Video - November 12th, 2011 [November 12th, 2011]
- H200 Hand Rehabilitation System - Testimonials - Clinical Focus - Video - November 13th, 2011 [November 13th, 2011]
- Coping with Brain Injury: Robots and Rehabilitation - Video - November 16th, 2011 [November 16th, 2011]
- Traumatic Brain Injury Rehabilitation using MediTouch HandTutor - Video - November 18th, 2011 [November 18th, 2011]
- Brain Injury Treatment Success | College Station Chiropractor Dr. David Bailey - Video - November 30th, 2011 [November 30th, 2011]
- Hyperbaric Oxygen Therapy (HBOT) corrects brain-injury. - Video - December 7th, 2011 [December 7th, 2011]
- Story of a Traumatic Brain Injury Recovery with Hyperbaric Oxygen (Part1/4) - Video - December 8th, 2011 [December 8th, 2011]
- Hyperbaric Oxygen Therapy Brain Injury - Video - December 10th, 2011 [December 10th, 2011]
- Redwood Extended Care Facility - Brain Injury Services - Video - December 10th, 2011 [December 10th, 2011]
- What If... Brain Injury Rehabilitation - Video - December 17th, 2011 [December 17th, 2011]
- Dangers in Self Medication - Young Adults with Lyme Disease - Leo J. Shea, III, PhD - Video - December 18th, 2011 [December 18th, 2011]
- Reducing Severe Traumatic Brain Injury in the US - Video - December 19th, 2011 [December 19th, 2011]
- Traumatic Brain Injury - Part 8 - Dr. R. Kohn, MD, Neurology - December 21st, 2011 [December 21st, 2011]
- Brain injury rehabilitation using Wii recreational therapy - Video - December 24th, 2011 [December 24th, 2011]
- CNS President/CEO Dr. Mark Ashley discusses how research shapes brain injury rehabilitation - Video - December 29th, 2011 [December 29th, 2011]
- Albert James De Meillon-Traumatic Brain Injury-Part 1 - Video - January 1st, 2012 [January 1st, 2012]
- Hope Beyond Trauma_Janie Smith - Video - January 10th, 2012 [January 10th, 2012]
- Neurofeedback adhd - Video - January 11th, 2012 [January 11th, 2012]
- We are the World, We ARE The Children - Video - January 11th, 2012 [January 11th, 2012]
- New Hopes for Treating Traumatic Brain Injury - Video - January 11th, 2012 [January 11th, 2012]
- NeuroRestorative's Robin Ray Featured on ABC in Southern Illinois - Video - January 13th, 2012 [January 13th, 2012]
- Careers at Origami Brain Injury Rehabilitation Center - Video - January 26th, 2012 [January 26th, 2012]
- Chris Persel discusses what makes CNS a leader in brain injury rehabilitation - Video - January 27th, 2012 [January 27th, 2012]
- Care for catastrophic injuries, spinal cord and traumatic brain injury - Video - January 27th, 2012 [January 27th, 2012]
- Military Tests Pressurized Chamber to Treat TBI - Video - January 27th, 2012 [January 27th, 2012]
- Richmond Traumatic Brain Injury Attorneys Applaud White House Research Initiative Targeting Veterans’ Health Issues - January 28th, 2012 [January 28th, 2012]
- Protect Your Brain...Why? - Video - January 30th, 2012 [January 30th, 2012]