On December 10, 2018 Seattle Genetics (Nasdaq: SGEN) and Takeda Pharmaceutical Co., Ltd. (TSE: 4502) are the third phase ECHELON ( BUSINESS WIRE ) – ( BUSINESS WIRE ) – Washington State Bothell and Massachusetts – -2 We will reported that the clinical trial data will be reported today at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Seattle Genetics, DEC 10, 2018, View Source [SID1234531994]). Frontline treatment with Adetetris (Brentuximab · Bodotin) in combination with CHP (cyclophosphamide, doxorubicin, prednisone) has been shown to be effective as a treatment for CHOP (CHOP), a current standard of care for CD30 expressing peripheral T cell lymphoma (PTCL) (PFS) and overall survival (OS) as compared to cyclophosphamide, cyclophosphamide, doxorubicin, vincristine, prednisone) and has an equivalent safety profile. These data were also published in the online edition of Lancet magazine . Adetters is an antibody drug complex (ADC) that targets CD30 expressed on the surface of several PTCLs.
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Good top line data of Phase 3 ECHELON-2 clinical trial has been announced in October 2018. In November 2018, Adetetrice received from U.S. Food and Drug Administration (FDA), in combination with CHP, untreated systemic anaplastic large cell lymphoma (sALCL), CD30 expressing PTCL (angioimmunoblastic T cell lymphoma, We included approval for adult patients with other unidentifiable PTCLs). The data of the ECHELON-2 trial is the basis of a partial change approval application (sBLA) of biological products, the FDA has reviewed the application under the real-time oncology review pilot program, and after two weeks from the completion of BLA application submission Approved within.
Dr. Stephen Horowitz (MD) of the Department of Internal Medicine Lymphoma of New York’s Memorial Sloan-Kettering Cancer Center says, "As a physician we are constantly seeking new strategies to address the unmet need of malignant blood cancer and Adeters offers a wide range of lymphomas and further benefits to patients with PTCL frontline therapy It is proved to be one of medicines.This study is important for patients because the doctor gets a new method for treating the initial patient of CD30-expressing PTCL which is a group of malignant cancers The data from ECHELON – 2 are superior for prolonging both progression – free survival and overall survival compared to CHOP, the current standard of therapy, when Adetetris and CHP are combined It is a multidrug chemotherapy regimen that we have been using for decades in treatment. "
Roger Dansey (MD), Seattle Genetics’ Chief Medical Officer (CMO), says: "This approval is the sixth case of malignant lymphoma indication and the second case of frontline treatment in combination with chemotherapy as an example of FDA approval of adsissus.The data announced today at ASH (Free ASH Whitepaper) is Adessetris Is a combination therapy that brings clinically meaningful benefits to untreated PTCL patients and can revolutionize treatment for these patients. "
Jesús Gómez-Navarro, vice president (MD), Takeda Pharmaceutical’s oncology clinical research and development manager, stated, "We are pleased to announce these remarkable results of the ECHELON-2 trial.These results will broaden the data on the effectiveness and safety of adetissus observed in various CD30 positive lymphomas. The trial showed clinically meaningful results and showed an improvement in overall survival for the first time as a Phase 3 randomized trial in PTCL frontline therapy.While establishing optimal therapy for PTCL was a challenge for the physician , These results will be a step forward in responding to the unmet need of this severely ill patient.With cooperation with regulators in the area where we operate our business, we offer promising new treatment options for PTCL patients I will like to try."
"ECHELON-2 trial: Randomized double-blinded active drug control 3, which compares Brentoximobetdin and CHP combination therapy (A + CHP) with CHOP for front line treatment of CD 30 positive peripheral T cell lymphoma patients Results of a Randomized, Double-Blind, Active-Controlled Phase 3 Study of Brentuximab Vedotin and CHP (A + CHP) Versus CHOP in the Frontline Treatment of Patients with CD 30 + Peripheral T- Cell Lymphomas) (abstract # 997, oral presentation at San Diego Convention Center Room 6F at 6:15 pm on Monday, December 3, 2018 at Pacific time)
The ECHELON-2 trial is an international randomized, double-blind, multicenter trial evaluating adetissus as part of a front line combination chemotherapy regimen in untreated CD30-expressing PTCL patients. The main endpoint was set as PFS by blinded independent central judgment (BICR), and the event stipulated the application of chemotherapy for disease progression, death, residual disease or disease progression. The primary secondary endpoint included PFS, complete remission (CR) rate, OS, objective response rate (ORR) in sALCL patients. In the ECHELON – 2 study, 452 patients (226 in each group) in 132 facilities in 17 countries in North America, Europe, Asia – Pacific, Middle East were incorporated. The median age of patients was 58 years old. The study included advanced patients (80 percent), with the majority of the patients suffering from sALCL (48 percent ALK negative, 22 percent ALK positive).
Dr. Stephen Horowitz is supposed to make a presentation, and the main test results published in Lancet magazine are as follows.
The main endpoint was achieved in the ECHELON-2 trial, and the combination therapy with Adeters and CHP showed a statistically significant improvement in PFS based on the evaluation by BICR (hazard ratio [HR] = 0.71, p value = 0.0110) . A 29% reduction in the risk of additional anticancer treatment required by disease progression, death, residual disease or disease progression.
After the follow-up period with a median of 36.2 months, the median PFS based on the assessment of BICR was 48.2 months (95% CI, 35.2 – unevaluable) in the combined administration group of Adetetris and CHP, 20.8 months (95% CI, 12.7 – 47.6). The 3 – year progression – free survival rate was 57.1% in Adeters + CHP group and 44.4% in control group.
Adsetris + CHP showed a statistically significant improvement in PFS (HR = 0.70, p value = 0.0096) based on the evaluation by the investigator.
The OS was statistically significantly superior to Adopteris + CHP group compared to CHOP (HR = 0.66, p value = 0.0244). The mortality risk is reduced by 34%.
After the median 42.1 month follow-up period, the median OS was not yet achieved in any group of trials. The estimated three-year OS was 76.8% for Adeters + CHP group and 69.1% for CHOP group.
All other major secondary endpoints were statistically significantly superior to adsissus + CHP group, including CR rate and ORR, in addition to PFS in sALCL patients. In the case of evaluation by BICR, the CR rate (68% versus 56%, respectively) and the ORR (83% versus 72% respectively) were significantly higher for patients in the Adeters + CHP group than for patients treated with CHOP (P value = 0.0066 and p value = 0.0032, respectively). In the case of evaluation by the investigator, the Advantis + CHP group and the CHOP group had comparable advantages for CR rate and ORR (p value = 0.0043 and p value = 0.0018, respectively).
Apart from stem cell transplantation or radiation therapy as a consolidation to strengthen the response to initial treatment, 74% of adetritis + CHP patients and 58% of CHOP patients respond to subsequent anticancer therapies for residual disease or disease progression I did not need it. 49 (22%) of the 226 patients who received CHOP received treatment followed by adetissus.
The safety profile of adetissus + CHP in the ECHELON-2 study was equivalent to CHOP and was consistent with Adhesetris’ established safety profile in combination with chemotherapy.
Frequently-expressed treatment-related adverse events (all grades) of 20% or more of patients in each group of Adetissus + CHP and CHOP included nausea (46 and 38% respectively), peripheral sensory neuropathy (45 and 41% , Neutropenia (38 percent each), diarrhea (38 and 20 percent respectively), constipation (29 and 30 percent respectively), alopecia (26 and 25 percent respectively), fever (26 and 19 percent respectively) Vomiting (26 and 17 percent respectively), fatigue (24 and 20 percent respectively), and anemia (21 and 16 percent respectively).
Neutropenia (35 and 34 percent respectively) and anemia (13 and 10 percent, respectively) were the most frequent cases of grade 3 or higher adverse events expressed in adetrice + CHP and CHOP groups.
The incidence and severity of neutropenia were comparable in both groups and were lower in the patient subset that received primary prevention with granulocyte colony stimulating factor. Feverty neutropenia has been reported in 41 adctetus + CHP patients (18 percent), 33 patients in the CHOP group (15 percent).
Novel expression or worsening of peripheral neuropathy events under treatment was seen in 117 patients (52 percent) in the adetritis + CHP group and 124 patients (55 percent) in the CHOP group, the majority of them with the highest severity grade 1 (64 and 71 percent respectively). Percentage of peripheral neuropathy returning below baseline in the last round of follow-up was 50% in Adetetrs + CHP group and 64% in CHOP group, median time to convergence was 17 weeks and 11.4 It was a week.
Adverse events leading to death are manifested in seven patients (3 percent) in Adessoris + CHP group and nine patients (4 percent) in CHOP group.
Please read the important safety information at the end of this press release , including framework warnings .
About T cell lymphoma
Lymphoma is a generic name that indicates cancer types occurring in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin’s lymphoma. There are over 60 subtypes in non-Hodgkin’s lymphoma and are classified roughly into two major groups, B-cell lymphomas arising from abnormal B lymphocytes and T cell lymphomas arising from abnormal T lymphocytes I will. There are many types of T cell lymphomas, some of which are extremely rare. T cell lymphoma may be aggressive (fast growing) or slow (slow growing). PTCL accounts for approximately 10% of non-Hodgkin lymphoma cases in Europe and the United States and 24% in Asia.
About Adessoris (Brentuximim · Bedchin)
Adetters is under extensive evaluation in over 70 clinical trials of CD30-expressing malignant tumor. These studies included a Phase 3 ECHELON-2 study completed as a front line treatment for peripheral T cell lymphoma (also known as mature T cell lymphoma), ECHELON-1 trial completed on untreated Hodgkin’s lymphoma , Phase 3 ALCANZA trial completed for skin T-cell lymphoma (CTCL) is included.
Adetters is an ADC that uses the proprietary technology of Seattle Genetics and binds anti-CD30 monoclonal antibody with the microtubule inhibitor monomethylauristatin E (MMAE) with a proteolytic cleavage linker. The linker system adopted by this ADC is designed to release MMAE when it is stable in blood and incorporated into CD30-expressing tumor cells.
Adetters Injection for intravenous injection received approval from FDA for six indications for adult patients. These indications include (1) untreated systemic anaplastic large cell lymphoma (sALCL), CD30 expressing peripheral T cell lymphoma (PTCL) (including angiogenic immunoblastic T cell lymphoma, other unidentifiable PTCL (2) untreated stage 3/4 classical Hodgkin lymphoma (cHL) (combined with doxorubicin, vinblastine, dacarbazine), (3) autologous hematopoietic stem cell transplantation (in combination with doxorubicin, Autologous HSCT) cHL with high risk of recurrence or progression after consolidation therapy, (4) patients who have failed autologous HSCT or who are not candidates for in-house HSCT and who have failed at least two multi-drug chemotherapy regimens in the past cHL, (5) sALCL after failure of one or more previous multi-drug chemotherapy regimens, (6) primary skin anaplastic large cell lymphoma (pcALCL) or CD30 (pcALCL) in patients who have undergone systemic therapy in the past Expressing bacteria Breath meat disease, and it will be.
Canadian Ministry of Health gives Adessetrs a conditional approval in 2013 with relapsed or refractory Hodgkin’s lymphoma and sALCL as an indication, and after autologous stem cell transplantation (ASCT) in Hodgkin lymphoma patients with a risk of recurrence or progression We give unconditional approval as consolidation therapy of.
Adetrice acquired a conditional marketing approval in October 2012 from the European Commission. These European-approved indications are: (1) Recurrent or refractory CD30-positive adult Hodgkin after at least two treatments after ASCT or when ASCT or multidrug chemotherapy is not a treatment option Treatment of lymphoma patients, (2) treatment of recurrent or refractory adult sALCL patients, (3) treatment of adult patients with CD30 positive Hodgkin lymphoma with a high risk of relapse / progression after ASCT, (4) at least one Treatment of adult patients with CD30 positive skin T cell lymphoma (CTCL) receiving systemic therapy, will be.
Adsetris has been approved by the regulatory authorities in 72 countries for recurrent / refractory Hodgkin’s lymphoma and sALCL for marketing approval. Please see the important safety information excerpt below including framework warning.
Seattle Genetics and Takeda Pharmaceutical are developing Adetetrice jointly. In accordance with the terms of the alliance agreement, Seattle Genetics reserves the right to commercialize Adetters in the US and Canada, and Takeda reserves the right to commercialize it elsewhere in the world. Seattle Genetics and Takeda co-borne the development cost of Adetritis at a ratio of 50 to 50, but exceptionally Takeda Pharmaceutical is responsible for developing costs in Japan independently.