SGEN Seattle Genetics Inc.

171.36
+2.33  (+1%)
Previous Close 169.03
Open 170.64
52 Week Low 63.02
52 Week High 175.64
Market Cap $29,662,721,535
Shares 173,101,783
Float 54,504,664
Enterprise Value $28,535,172,380
Volume 319,063
Av. Daily Volume 1,399,275
Stock charts supplied by TradingView

Upcoming Catalysts

Drug Stage Catalyst Date
GSK’916 - belantamab mafodotin (BCMA)
Multiple myeloma
PDUFA priority review
PDUFA priority review
Premium membership is required to view catalyst dates, analyst ratings, earnings dates and cash burn data. Click here to unlock and sign up to a 14-day FREE TRIAL.

Drug Pipeline

Drug Stage Notes
Tisotumab Vedotin (innovaTV 204 )
Cervical Cancer
Phase 2
Phase 2
Phase 2 data noted 24% ORR with a median duration of response of 8.3 months.
SEA-TGT
Solid tumors
Phase 1
Phase 1
Phase 1 trial initiation announced June 18, 2020.
SGN-B6A
Solid Tumors
Phase 1
Phase 1
Phase 1 trial initiation announced June 18, 2020.
ADCETRIS and Opdivo CM-744
Relapsed/Refractory Classical Hodgkin Lymphoma
Phase 2
Phase 2
Phase 2 presentation at EHA June 15, 2019.
Ladiratuzumab Vedotin
Triple negative breast cancer (TNBC)
Phase 1/2
Phase 1/2
Phase 1b/2 trial has been initiated.
ADCETRIS
Hodgkin lymphoma and Anaplastic large cell lymphoma
Approved
Approved
Approval announced August 19, 2011.
ADCETRIS - AETHERA
Post-transplant Hodgkin lymphoma (HL) cancer
Approved
Approved
Approved August 17, 2015 under priority review.
ADCETRIS in combination with chemotherapy - ECHELON-2
Frontline CD30-positive mature T-cell lymphomas - cancer
Approved
Approved
FDA Approval announced November 16, 2018.
ADCETRIS in combination with chemotherapy ECHELON-1
Frontline Hodgkin lymphoma
Approved
Approved
sBLA approval announced March 20, 2018. PDUFA date under priority review was May 1, 2018.
Tisotumab Vedotin (innovaTV 201)
Recurrent Cervical Cancer
Phase 1/2
Phase 1/2
Phase 1/2 updated data presented at ESMO October 20. 2018.
Tucatinib in combination with trastuzumab and capecitabine
HER2+ Metastatic Breast Cancer (MBC)
Approved
Approved
FDA Approval announced April 17, 2020.
SGN-LIV1A + KEYTRUDA
First-line triple negative breast cancer (TNBC)
Phase 1/2
Phase 1/2
Phase 1/2 trial initiated early 2018.
Enfortumab vedotin and Keytruda EV-103
Urothelial cancer
Phase 1/2
Phase 1/2
Phase 1/2 data noted Overall response rate 73%; Complete response rate 16% (partial response rate 58%).
Enfortumab vedotin - EV-202
Solid tumors
Phase 2
Phase 2
Phase 2 trial initiated January 2020.
Enfortumab vedotin and Keytruda - EV-301
Urothelial cancer
Phase 3
Phase 3
Phase 3 enrolment completed in January 2020.
Tisotumab Vedotin (innovaTV 207)
Solid tumors
Phase 2
Phase 2
Phase 2 dosing has commenced - noted July 12, 2018.
Enfortumab vedotin
Urothelial cancer
Approved
Approved
FDA Approval announced December 18, 2019.
Tucatinib - MOUNTAINEER
HER2 amplified metastatic colorectal cancer
Phase 2
Phase 2
Phase 2 data at ESMO noted 52% ORR, median PFS 8.1 months, OS of 18.7 months.
Tucatinib + ado-trastuzumab emtansine (T-DM1, Kadcyla), - HER2CLIMB-02
HER2+ Metastatic Breast Cancer (MBC)
Phase 3
Phase 3
Phase 3 trial initiation announced October 10, 2019.
Enapotamab vedotin
Solid tumors
Phase 1/2
Phase 1/2
Phase 1/2 initial data presented at IASLC 2019 WCLC September 8, 2019.
SGN-CD19A
Frontline DLBCL cancer
Phase 2
Phase 2
Phase 2 trial initiated 3Q 2016.
(Tucatinib ONT-380) and T-DM1
HER2+ Metastatic Breast Cancer (MBC)
Phase 1b
Phase 1b
Phase 1b updated data at SABCS December 7, 2017.
Enfortumab vedotin - EV-301
Urothelial cancer
Phase 3
Phase 3
Phase 3 trial initiation announced July 9, 2018.
Polatuzumab vedotin and bendamustine plus Rituxan (rituximab)
Diffuse large B-cell lymphoma (DLBCL)
Approved
Approved
FDA approval announced June 10, 2019.
ADCETRIS
Cancer - ALCANZA trial for relapsed CD30-positive cutaneous T-cell lymphoma
Approved
Approved
Approval announced November 9, 2017.
Vadastuximab Talirine (CASCADE)
Acute myeloid leukemia (AML) - cancer
Phase 3
Phase 3
Phase 3 trial discontinued due to higher rate of deaths - June 19, 2017.
Vadastuximab Talirine (SGN-CD33A)
Myelodysplastic syndrome (MDS)
Phase 1/2
Phase 1/2
Phase 1/2 clinical hold placed on December 27, 2016 was lifted March 6, 2017. Enrollment halted June 19, 2017 due to safety.
SGN-LIV1A (I-SPY 2)
Neoadjuvant for newly diagnosed Stage 2 or 3 HER2 negative breast cancer
Phase 2
Phase 2
Phase 2 trial to be initiated.

Latest News

  1. - Full Data to be Presented at an Upcoming Medical Meeting -

    Seattle Genetics, Inc. (NASDAQ:SGEN) today announced positive topline results from the phase 2 single-arm clinical trial known as innovaTV 204 evaluating tisotumab vedotin administered every three weeks for the treatment of patients who have relapsed or progressed on or after prior treatment for recurrent or metastatic cervical cancer. Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review [95% Confidence Interval: 15.9%-33.3%] with a median duration of response (DOR) of 8.3 months. The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia, epistaxis (nose bleeds), nausea, conjunctivitis…

    - Full Data to be Presented at an Upcoming Medical Meeting -

    Seattle Genetics, Inc. (NASDAQ:SGEN) today announced positive topline results from the phase 2 single-arm clinical trial known as innovaTV 204 evaluating tisotumab vedotin administered every three weeks for the treatment of patients who have relapsed or progressed on or after prior treatment for recurrent or metastatic cervical cancer. Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review [95% Confidence Interval: 15.9%-33.3%] with a median duration of response (DOR) of 8.3 months. The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia, epistaxis (nose bleeds), nausea, conjunctivitis, fatigue and dry eye. The data will be submitted for presentation at an upcoming medical meeting.

    Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor, which is expressed on cervical cancer and can promote tumor growth, angiogenesis and metastases.1 Standard therapies for previously treated recurrent and/or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months, in an all-comers population.1-8 Tisotumab vedotin is being developed by Seattle Genetics in collaboration with Genmab.

    "Available therapies upon progression after first line chemotherapy in recurrent or metastatic cervical cancer are limited, and there is a significant unmet need for new treatment options," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "Tisotumab vedotin has demonstrated clinically meaningful and durable objective responses with a manageable safety profile, and we look forward to discussing with the FDA the potential submission of a Biologics License Application to support an accelerated approval."

    Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.9 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.10 Routine medical examinations and the human papillomavirus (HPV) vaccine have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic.

    Additional clinical trials of tisotumab vedotin are currently enrolling patients, including in combination with pembrolizumab, carboplatin or bevacizumab, and with a weekly dosing schedule in patients with locally advanced or metastatic cervical cancer. Tisotumab vedotin is also being evaluated in other tissue factor expressing tumor types, including ovarian and other solid tumors.

    About innovaTV 204 Trial

    The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

    The study was conducted in collaboration with European Network of Gynaecological Oncological Trial Groups (ENGOT) and Gynecologic Oncology Group (GOG). For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

    About Tisotumab Vedotin

    Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seattle Genetics' ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a protein that can promote tumor growth, angiogenesis and metastases.1 Based on its high expression on many solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seattle Genetics, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

    Tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in a range of solid tumors, including recurrent and/or metastatic cervical cancer, ovarian cancer and in combination with other commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three weeks dosing schedule.

    About Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEVTM (enfortumab vedotin-ejfv) use the company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSATM (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential submission of a BLA to the FDA under the FDA's accelerated approval program and the potential for regulatory approval of tisotumab vedotin based on the innovaTV 204 trial; the therapeutic potential of tisotumab vedotin, its possible benefits and uses, including as monotherapy or in combination with other agents, and in other tumor types or with a weekly dosing regimen, and the tisotumab vedotin future development program. 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 possibility that the data from innovaTV 204 may not be sufficient to support accelerated approval; the possibility of impediments or delays in the submission of a potential BLA to the FDA; the risk of adverse events, including the potential for newly-emerging safety signals; delays, setbacks or failures in clinical development activities for a variety of reasons, including the difficulty and uncertainty of pharmaceutical product development, adverse regulatory action, possible required modifications to clinical trials, failure to properly conduct or manage clinical trials and failure of clinical results to support continued development or regulatory approvals. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's 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.

    References:

    1 Van de Berg YW et al. Blood 2012;119:924.

    2 Miller et al., Gynecol Oncol 2008; 110:65.

    3 Bookman et al., Gynecol Oncol 2000; 77:446.

    4 Garcia et al., Am J Clin Oncol 2007; 30:428.

    5 Monk et al., J Clin Oncol 2009; 27:1069.

    6 Santin et al., Gynecol Oncol 2011; 122:495.

    7 Schilder et al., Gynecol Oncol 2005; 96:103

    8 Chung HC et al. J Clin Oncol 2019; 37:1470.

    9 National Cancer Institute SEER. "Cancer Stat Facts: Cervix Uteri Cancer." Available at https://seer.cancer.gov/statfacts/html/cervix.html. Last accessed April 2020.

    10 Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 countries https://www.iarc.fr/news-events/global-cancer-statistics-2018-globocan-estimates-of-incidence-and-mortality-worldwide-for-36-cancers-in-185-countries/.

    View Full Article Hide Full Article
  2. - Effector Function Enhanced Anti-TIGIT Antibody -

    - Antibody-Drug Conjugate Targeting Integrin Beta-6 -

    - Both Drug Candidates to be Evaluated in Multiple Tumor Types -

    Seattle Genetics, Inc. (NASDAQ:SGEN) today announced dosing of the first patient in a phase 1 clinical trial evaluating investigational agent SEA-TGT, also known as SGN-TGT, an anti-TIGIT antibody for patients with solid tumors and lymphomas. TIGIT (T-cell immune receptor with Ig and ITIM domains) is an inhibitory immune receptor that is emerging as a clinically relevant immuno-oncology target. SEA-TGT is a nonfucosylated human IgG1 antibody that uses the Company's proprietary Sugar Engineered Antibody (SEA) technology. The Company also announced the dosing of the first…

    - Effector Function Enhanced Anti-TIGIT Antibody -

    - Antibody-Drug Conjugate Targeting Integrin Beta-6 -

    - Both Drug Candidates to be Evaluated in Multiple Tumor Types -

    Seattle Genetics, Inc. (NASDAQ:SGEN) today announced dosing of the first patient in a phase 1 clinical trial evaluating investigational agent SEA-TGT, also known as SGN-TGT, an anti-TIGIT antibody for patients with solid tumors and lymphomas. TIGIT (T-cell immune receptor with Ig and ITIM domains) is an inhibitory immune receptor that is emerging as a clinically relevant immuno-oncology target. SEA-TGT is a nonfucosylated human IgG1 antibody that uses the Company's proprietary Sugar Engineered Antibody (SEA) technology. The Company also announced the dosing of the first patient in a phase 1 clinical trial evaluating investigational agent SGN-B6A, an antibody-drug conjugate (ADC) targeting integrin beta-6, which is overexpressed in numerous solid tumors and has been demonstrated to be a negative prognostic indicator across a diverse range of cancers.

    Preclinical data indicate that SEA-TGT has enhanced effector function enabled by the Company's SEA technology. These data indicate that SEA-TGT may have best-in-class potential through enhanced depletion of TIGIT-positive regulatory T-cells (Tregs), distinct immune changes including amplified naïve and memory T-cell responses, and induction of innate immune cell activation. Curative anti-tumor activity in preclinical models was observed as a single agent and in combination with a PD-1 checkpoint inhibitor. These data support potential for improved monotherapy and combinatorial clinical activity as compared to a non-enhanced TIGIT antibody.

    SGN-B6A is an ADC targeting integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE). In preclinical research, this ADC has demonstrated in vivo activity in models spanning a range of antigen expression levels and tumor types.

    "We believe that anti-TIGIT antibodies may have an important therapeutic role in the evolving immuno-oncology landscape," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "SEA-TGT utilizes our novel SEA technology, which in preclinical research has demonstrated enhanced effector function that potentially differentiates it from other TIGIT antibodies in the clinic. The initiation of clinical trials for both SEA-TGT and the ADC, SGN-B6A, underscore our commitment to advancing novel drug candidates from our pipeline into clinical testing."

    SEA-TGT Phase 1 Trial

    The phase 1 trial of SEA-TGT will evaluate the safety and anti-tumor activity of SEA-TGT as a single agent as well as in combination with the anti-PD-1 antibody, pembrolizumab. The phase 1 trial will evaluate SEA-TGT in advanced solid tumors and lymphomas, including non-small cell lung cancer, gastric carcinoma, Hodgkin and selected non-Hodgkin lymphomas. The study is currently open in multiple sites in the United States and is expected to enroll approximately 111 participants. More information about the study of SEA-TGT is available at clinicaltrials.gov.

    SGN-B6A Phase 1 Trial

    SGN-B6A is an ADC targeting integrin beta-6 to deliver the clinically validated payload MMAE. The phase 1 trial will evaluate SGN-B6A in solid tumors, including non-small cell lung cancer, head and neck squamous cell cancer, breast, esophageal, ovarian, bladder, cervical and gastric cancers. The study is currently open in multiple sites in the United States and is expected to enroll approximately 235 participants. More information about the study of SGN-B6A is available at clinicaltrials.gov.

    About Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEV™ (enfortumab vedotin-ejfv) use the Company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSA™ (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to therapeutic potential of SEA-TGT and SGN-B6A, their possible safety, efficacy, and therapeutic uses and anticipated development activities including the enrollment of patients in the Company's phase 1 studies, future clinical trials and intended regulatory actions. 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 risk of adverse events or safety signals, the inability to show sufficient activity in clinical trials and the possibility of adverse regulatory actions as product candidates are evaluated in clinical trials even after promising results in preclinical research. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the Company's 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.

    View Full Article Hide Full Article
  3. Seattle Genetics, Inc. (NASDAQ:SGEN) announced today that management will participate in a fireside chat during the virtual Goldman Sachs 41st Annual Global Healthcare Conference on Tuesday, June 9, 2020 at 11:20 a.m. Eastern Time. The presentation will be webcast live and available for replay from Seattle Genetics' website at www.seattlegenetics.com in the Investors section.

    About Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEV (enfortumab vedotin-ejfv) use the company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved…

    Seattle Genetics, Inc. (NASDAQ:SGEN) announced today that management will participate in a fireside chat during the virtual Goldman Sachs 41st Annual Global Healthcare Conference on Tuesday, June 9, 2020 at 11:20 a.m. Eastern Time. The presentation will be webcast live and available for replay from Seattle Genetics' website at www.seattlegenetics.com in the Investors section.

    About Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEV (enfortumab vedotin-ejfv) use the company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSA (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    View Full Article Hide Full Article
  4. - TUKYSA Combination Reduced Risk of Cancer Progression in the Brain or Death by Two-Thirds, Doubled Response Rate and Reduced Risk of Death by Nearly Half Compared to Standard Therapy Alone -

    - Published Simultaneously in the Journal of Clinical Oncology and Presented in an Oral Session During the Virtual Scientific Program of the 2020 ASCO Annual Meeting -

    - First Anti-HER2 Oral Therapy in Combination with Standard Medicines to Improve Overall and Progression-Free Survival in Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases -

    Seattle Genetics, Inc. today announced positive results from exploratory analyses of intracranial efficacy, including survival, in patients with HER2-positive metastatic breast…

    - TUKYSA Combination Reduced Risk of Cancer Progression in the Brain or Death by Two-Thirds, Doubled Response Rate and Reduced Risk of Death by Nearly Half Compared to Standard Therapy Alone -

    - Published Simultaneously in the Journal of Clinical Oncology and Presented in an Oral Session During the Virtual Scientific Program of the 2020 ASCO Annual Meeting -

    - First Anti-HER2 Oral Therapy in Combination with Standard Medicines to Improve Overall and Progression-Free Survival in Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases -

    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)

    (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 Women's 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 TUKYSA's 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:

    • a 42 percent reduction in the risk of death
    • a 68 percent reduction in the risk of CNS disease progression (a delay in progression in the brain) or death
    • a more than doubling of intracranial response rate (47 percent vs. 20 percent) for patients who had active measurable intracranial lesions at baseline

    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

    Endpoint TUKYSA Arm (TUKYSA + trastuzumab + capecitabine)

    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

    • Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.



      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.
    • Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 5% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.



      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.
    • Embryo-Fetal Toxicity – TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.

    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

    • Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
    • Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
    • CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
    • P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.

    Use in Specific Populations

    • Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
    • Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
    • Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.

    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 people's 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 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 company's 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.

      


    1 TUKYSA [package insert]. Bothell, WA: Seattle Genetics, Inc.

    2 Cancer Facts & Figures 2020. American Cancer Society website. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed May 28, 2020.

    3 Loibli S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.

    4 Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177-82.

    5 Breast Cancer HER2 Status. American Cancer Society website. www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed May 28, 2020.

    6 Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.

    7 Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.

    8 Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.

    9 Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Mol Cancer Ther 2020;19:976-987.

    View Full Article Hide Full Article
  5. Seattle Genetics, Inc. (NASDAQ:SGEN) today announced highlights from 12 presentations showcasing its research and development portfolio of novel targeted therapies and antibody-drug conjugate (ADC) technology advances and innovation will be presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting II being held June 22-24, 2020. Registration information to attend the virtual sessions can be found here.

    "We will have a strong presence at the AACR annual meeting with 12 data presentations highlighting our leadership in antibody-drug conjugate innovation and the depth and potential of our growing oncology pipeline of targeted therapies," said Scott Peterson, Ph.D., Senior Vice President of Research at Seattle Genetics…

    Seattle Genetics, Inc. (NASDAQ:SGEN) today announced highlights from 12 presentations showcasing its research and development portfolio of novel targeted therapies and antibody-drug conjugate (ADC) technology advances and innovation will be presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting II being held June 22-24, 2020. Registration information to attend the virtual sessions can be found here.

    "We will have a strong presence at the AACR annual meeting with 12 data presentations highlighting our leadership in antibody-drug conjugate innovation and the depth and potential of our growing oncology pipeline of targeted therapies," said Scott Peterson, Ph.D., Senior Vice President of Research at Seattle Genetics. "Of key importance, a number of presentations will feature advances in our drug linker and payload components of ADCs. Building on our expertise in CD30 targeted therapies, data will be presented from a new CD30-directed ADC that employs our novel camptothecin ADC technology and is being investigated as a potential future treatment option in CD30-expressing lymphomas."

    Dr. Peterson added, "In addition to our ADC technologies, we will also be presenting preclinical data highlighting the activity of our HER2 selective tyrosine kinase inhibitor tucatinib in preclinical models of HER2 mutant driven cancers and in the CNS setting. We look forward to sharing these presentations with the community at the second AACR virtual meeting."

    Abstracts can be found at www.aacr.org and include the following poster presentations below.

    New ADC Technology Advances

    Abstract Title: Novel Framework for Quantifying Synergy in High-Throughput Drug Combination Cytotoxicity Experiments (Abstract #835)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Clinical and Preclinical Precision Medicine: Next-Generation Sequencing, Functional, and Pharmacogenomics

    Abstract Title: Discovery of a Tripeptide-Based Camptothecin Drug-Linker for Antibody-Drug Conjugates with Potent Antitumor Activity and a Broad Therapeutic Window (Abstract #2885)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Antibody Drug Conjugates

    Abstract Title: Characterization of Payload Release from a Novel Camptothecin Drug-Linker (Abstract #2895)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Antibody Drug Conjugates

    Pipeline Programs

    Abstract Title: SGN-CD30C, a New CD30-Directed Camptothecin Antibody-Drug Conjugate (ADC), Shows Strong Anti-Tumor Activity and Superior Tolerability in Preclinical Studies (Abstract #2889)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Antibody Drug Conjugates

    Abstract Title: Utilizing PDX Models to Better Understand Factors that Predict Response to SGN-CD228A, an Antibody-Drug Conjugate (ADC) for Solid Tumors (Abstract #2888)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Antibody Drug Conjugates

    Abstract Title: SGN-B6A: A New MMAE ADC Targeting Integrin Beta-6 in Multiple Carcinoma Indications (Abstract #2906)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Antibody Drug Conjugates

    Abstract Title: SEA-CD40 is a Non-Fucosylated Anti-CD40 Antibody with Potent Pharmacodynamic Activity in Preclinical Models and Patients with Advanced Solid Tumors (Abstract #5535)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Immune Response to Therapies 1

    Commercial-Stage Programs

    Abstract Title: Preclinical Characterization of Tucatinib in HER2-Amplified Xenograft and CNS Implanted Tumors (Abstract #1962)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Small Molecule Therapeutic Agents

    Abstract Title: Tucatinib Inhibits Creatinine and Metformin Renal Tubule Secretion but has No Effect on Renal Function (GFR) (Abstract #3015)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Pharmacokinetics / Pharmacodynamics

    Abstract Title: Tucatinib Inhibits CYP3A, CYP2C8 and P-gp-Mediated Elimination and is Impacted by CYP2C8 Inhibition in Healthy Volunteers (Abstract #3016)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Pharmacokinetics / Pharmacodynamics

    Abstract Title: Tucatinib, a Selective Small Molecule HER2 Inhibitor, is Active in HER2 Mutant Driven Tumors (Abstract #4222)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Tyrosine Kinase and Phosphatase Inhibitors

    Abstract Title: Enfortumab Vedotin, an Anti-Nectin-4 ADC Demonstrates Bystander Cell Killing and Immunogenic Cell Death Anti-Tumor Activity Mechanisms of Action in Urotherlial Cancers (Abstract #5581)

    Date and Time:
    Monday, June 22, 9:00 a.m.-6:00 p.m. PT

    Session: Immunotherapy

    About Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEV™ (enfortumab vedotin-ejfv) use the company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSA™ (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the possible utility or application of the Company's technologies to develop therapeutic agents, the therapeutic potential of investigational agents and products, the Company's ADC leadership, future development activities and growing pipeline. 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, including the risks that the Company may experience delays in its planned clinical trial initiations or otherwise experience failures or setbacks in its preclinical and clinical development programs due to the potential lack of efficacy or risk of adverse events or other factors. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's 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.

    View Full Article Hide Full Article
View All Seattle Genetics Inc. News