|Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Frontline HL and MTCL Clinical Development Programs and Antibody-Drug Conjugate (ADC) Collaborator Data at ASCO Annual Meeting|
-ADCETRIS Phase 3 ECHELON-1 and ECHELON-2 Trials Designed to Redefine Standard of Care for Frontline Treatment of HL and MTCL-
-Genentech Presents Encouraging Phase 1 Data from Two ADC Candidates Utilizing Seattle Genetics’ Technology-
“ADCs represent an innovative and growing field in the fight against
cancer, which is evident by the interest in this therapeutic approach at
Phase III Trial of Brentuximab Vedotin Plus Doxorubicin, Vinblastine, and Dacarbazine (A+AVD) Versus Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) as Front-line Treatment for Advanced Classical Hodgkin Lymphoma (HL) (Abstract #TPS8612)
Recent phase 1 data presented at the 2012
Phase III Trial of Brentuximab Vedotin and CHP Versus CHOP in the Frontline Treatment of Patients with CD30+ Mature T-Cell Lymphomas (MTCL) (Abstract #TPS8611)
Recent phase 1 data presented at the 2012 ASH Annual Meeting
demonstrated that ADCETRIS in combination with cyclophosphamide,
doxorubicin and prednisone (A+CHP) in the frontline treatment of MTCL
was associated with a manageable safety profile and 100 percent
objective response rate, including 88 percent CRs. A global phase 3
study, called ECHELON-2, is an ongoing randomized, double-blind,
placebo-controlled, multi-center trial designed to investigate A+CHP
versus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)
as frontline therapy in patients with CD30-expressing MTCL.
Approximately 300 patients (approximately 150 patients per treatment
arm) will be randomized to receive A+CHP or CHOP for six to eight cycles
every three weeks. The primary endpoint is progression-free survival
(PFS) per independent review facility assessment using the Revised
Response Criteria for malignant lymphoma. Secondary endpoints include
OS, CR rate and safety. The trial is being conducted in
ADCETRIS is currently not approved for frontline treatment of HL and MTCL. For more information about ECHELON-1 and ECHELON-2, visit www.clinicaltrials.gov.
A Phase I Study of the Safety and Pharmacokinetics of DNIB0600A, an Anti-Napi2b-vc-MMAE Drug Conjugate, in Patients with Non-Small Cell Lung Cancer (NSCLC) and Platinum-Resistant Ovarian Cancer (OC) (Abstract #2507)
A phase 1 clinical trial is being conducted by Genentech to evaluate the safety and activity of DNIB0600A (RG7599) in patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC). DNIB0600A is an ADC consisting of an anti-NaPi2b monoclonal antibody conjugated to the cytotoxic agent MMAE using Seattle Genetics’ ADC technology. In this analysis, 46 patients were evaluable (30 OC, 16 NSCLC), with 30 patients (14 OC, 16 NSCLC) in the dose-escalation cohorts and 16 patients (all OC) in the dose expansion cohort.
Key findings presented in an oral presentation included:
A Phase I Study of the Safety and Pharmacokinetics of DSTP3086S, an Anti-STEAP1 Antibody-Drug Conjugate (ADC), in Patients with Metastatic Castration-Resistant Prostate Cancer (CRPC) (Abstract #5020)
A phase 1 clinical trial is being conducted by Genentech to evaluate the safety and activity of DSTP3086S (RG7450) in patients with metastatic castrate-resistant prostate cancer (CRPC). DSTP3086S is an ADC candidate consisting of an anti-STEAP1 monoclonal antibody conjugated to the cytotoxic agent MMAE using Seattle Genetics’ ADC technology. In this analysis, 28 patients were evaluable from the dose-escalation portion of this ongoing trial.
Key findings included:
The phase 1 trials evaluating both DNIB0600A and DSTP3086S are ongoing. For more information, visit www.clinicaltrials.gov.
ADCETRIS (brentuximab vedotin) 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 Seattle Genetics’ 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 tumor cells.
ADCETRIS was granted accelerated approval by the
ADCETRIS was granted conditional marketing authorization by the
ADCETRIS is being evaluated in more than 20 ongoing clinical trials across both corporate and investigator-sponsored studies. The trials are designed to broadly evaluate the potential of ADCETRIS in earlier lines of its approved indications as well as in many additional types of CD30-positive malignancies, including cutaneous T-cell lymphoma (CTCL), B-cell lymphomas and mature T-cell lymphomas (MTCL). For more information, visit www.clinicaltrials.gov. The clinical trials include:
About Hodgkin and Non-Hodgkin Lymphomas
Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: Hodgkin
lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished
from other types of lymphoma by the presence of one characteristic type
of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell
generally expresses CD30. Non-Hodgkin lymphomas are broadly divided into
two major groups: B-cell lymphomas, which develop from abnormal
B-lymphocytes, and T-cell lymphomas, which develop from abnormal
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the company’s ongoing
clinical trials. Factors that may cause such a difference include that
adverse events may occur that require modification or discontinuation of
clinical trials. More information about the risks and uncertainties