StemCell Therapy

BOTHELL, Wash.--(BUSINESS WIRE)--Seagen Inc. (Nasdaq:SGEN) today announced multiple ADCETRIS (brentuximab vedotin) data presentations at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually December 5-8, 2020. Data presentations include five-year updates from the phase 3 ECHELON-1 and ECHELON-2 clinical trials evaluating ADCETRIS plus a chemotherapy combination regimen in frontline advanced stage classical Hodgkin lymphoma (HL) and CD30-expressing frontline peripheral T-cell lymphoma (PTCL), respectively. In addition, first results were presented from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with Opdivo (nivolumab) in relapsed or refractory mediastinal gray zone lymphoma (MGZL), a rare type of non-Hodgkin lymphoma that express CD30 with no standard of care. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of non-Hodgkin lymphoma, including PTCL. ADCETRIS is being evaluated globally in more than 70 corporate- and investigator-sponsored clinical trials across multiple settings in lymphoma and other indications. ADCETRIS and Opdivo are not approved alone or in combination for the treatment of relapsed or refractory MGZL.

After five years of follow-up, an important clinical milestone, both the ECHELON-1 and ECHELON-2 clinical trials demonstrate that ADCETRIS plus chemotherapy resulted in superior and durable outcomes when compared with standard chemotherapy regimens, said Roger Dansey, M.D., Chief Medical Officer at Seagen. As most relapses in Hodgkin lymphoma occur within five years of frontline treatment, the results of the ECHELON-1 study suggest that patients treated with ADCETRIS plus chemotherapy are more likely to experience long-term remissions compared to those treated with the ABVD regimen.

Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study (Abstract #2973, poster presentation on Monday, December 7, 2020)

The ECHELON-1 clinical trial is evaluating ADCETRIS in combination with AVD (Adriamycin [doxorubicin], vinblastine, dacarbazine) compared to ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) in patients with Stage III or IV frontline classical HL. As previously reported, the ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified progression-free survival (PFS) compared to the control arm of ABVD as assessed by independent review facility (IRF; hazard ratio (HR), 0.77; p=0.035). A five-year exploratory analysis was conducted to examine PFS outcomes per investigator assessment in the intent-to-treat population of 1,334 patients. Results include:

The ECHELON-2 Trial: 5-Year Results of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30-Positive Peripheral T-Cell Lymphoma (Abstract #1150, poster presentation on Saturday, December 5, 2020)

The ECHELON-2 clinical trial is evaluating ADCETRIS in combination with CHP (cyclophosphamide, Adriamycin [doxorubicin], prednisone) compared to CHOP (cyclophosphamide, Adriamycin [doxorubicin], vincristine, prednisone) in frontline CD30-expressing PTCL. As previously reported, the ECHELON-2 trial met its primary endpoint with the combination of ADCETRIS plus CHP resulting in a statistically significant improvement in PFS versus the control arm of CHOP per blinded independent central review (HR, 0.71; p=0.0110). A five-year post-hoc exploratory analysis was conducted to examine PFS outcome and overall survival (OS) per investigator assessment in the intent-to-treat population of 452 patients. Key findings include:

Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Mediastinal Gray Zone Lymphoma: Primary Efficacy and Safety Analysis of the Phase 2 CheckMate 436 Study (Abstract #2045, poster presentation on Sunday, December 6, 2020)

Data from the ongoing CheckMate 436 phase 2 clinical trial of 10 patients with relapsed or refractory MGZL who received a combination of ADCETRIS plus Opdivo treatment after autologous stem cell transplant or two or more lines of multi-agent chemotherapy if ineligible for transplant will be presented for the first time. Patients were treated once every three weeks or until disease progression or unacceptable toxicity. The median age of patients was 35 years. Key findings include:

About ADCETRIS

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagens proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.

ADCETRIS for injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with previously untreated sALCL in combination with cyclophosphamide, doxorubicin and prednisone (CHP), (5) for the treatment of adult patients with relapsed or refractory sALCL, and (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See U.S. important safety information, including Boxed Warning, below.

Seagen and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Administer G-CSF primary prophylaxis beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Most Common (20% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.

About Seagen

Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in peoples lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the companys marketed products and robust pipeline, visit http://www.seagen.com and follow @SeagenGlobal 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 therapeutic potential of ADCETRIS plus chemotherapy combination regimens in frontline advanced stage Hodgkin lymphoma, and frontline peripheral T-cell lymphoma, and in combination with Opdivo (nivolumab) in relapsed or refractory mediastinal gray zone lymphoma (MGZL). Actual results or developments may differ materially from those projected or implied in these forward-looking statements due to factors such as unexpected adverse events, adverse regulatory actions, the degree of utilization and adoption of an approved treatment regimen by prescribing physicians, the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results and risks related to the duration and severity of the COVID-19 pandemic. More information about the risks and uncertainties faced by Seagen is contained under the caption Risk Factors included in the Companys Quarterly Report on Form 10-Q for the quarter ended September 30, 2020 filed with the Securities and Exchange Commission. Seagen 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.

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Seagen Announces Multiple ADCETRIS (brentuximab vedotin) Presentations at the 2020 ASH Annual Meeting - Business Wire

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