1stOncology™: Cancer Intelligence Service – Page 14473 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Seattle Genetics and Takeda present good data on Phase 3 ECHELON-2 clinical trial which examines adetissus (Brentuximab · bedcine) in front line treatment of CD30 expressing peripheral T cell lymphoma

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

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.

AngioDynamics to Report Fiscal 2019 Second Quarter Financial Results on January 4, 2019

On December 10, 2018 AngioDynamics, Inc. (NASDAQ: ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, and oncology, reported that it will report financial results for the second quarter of fiscal year 2019 before the market open on Friday, January 4, 2019 (Press release, AngioDynamics, DEC 10, 2018, View Source [SID1234531993]). The Company’s management will host a conference call at 8:00 a.m. ET the same day to discuss the results.

To participate in the conference call, dial 1-877-407-0784 (domestic) or 1-201-689-8560 (international) and refer to the passcode 13685683.

This conference call will also be webcast and can be accessed from the "Investors" section of the AngioDynamics website at www.angiodynamics.com. The webcast replay of the call will be available at the same site approximately one hour after the end of the call.

A recording of the call will also be available from 11:00 a.m. ET on Friday, January 4, 2019, until 11:59 p.m. ET on Friday, January 11, 2019. To hear this recording, dial 1-844-512-2921 (domestic) or 1-412-317-6671 (international) and enter the passcode 13685683.

Data presented at the ASH 2018 Annual Meeting confirm treatment benefits of first-line treatment with IMBRUVICA ® ▼ (ibrutinib) -based therapy for all patient populations with CLL

On December 10, 2018 Janssen Pharmaceutical Companies of Johnson & Johnson reported new findings from three key studies on IMBRUVICA (ibrutinib) in the treatment of chronic lymphocytic leukemia (CLL), a difficult-to-treat form of blood cancer and cancer most common form of leukemia in adults (Press release, Johnson & Johnson, DEC 10, 2018, View Source [SID1234531992]). 1 The findings were presented at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), held in San Diego, California.

The results of the National Cancer Institute’s (NCI) funded Phase III study (E1912) led by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) were presented during the late-breaker lecture series. The study evaluated doses of ibrutinib plus rituximab compared to chemotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) from previously untreated CLL patients aged 70 years or younger. In a three-year follow-up study, data for ibrutinib plus rituximab showed significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to FCR. 2

The data from the Phase III iLLUMINATE (PCYC-1130) study were also published in a lecture series and at the same time in the journal The Lancet Oncology . The results showed significantly prolonged progression-free survival in patients taking newly diagnosed CLL in additions of ibrutinib plus obinutuzumab compared with chlorambucil plus obinutuzumab. 3 These data recently supported the submission of an application for Type II amendments to the European Medicines Agency (EMA) to request the approval of extended use of ibrutinib in combination with obinutuzumab in previously untreated CLL patients.

In addition, data from the Phase Ib / II study and its extension study (PCYC-1102, PCYC-1103) in patients with newly diagnosed and relapsed / refractory (r / r) CLL and monotherapy showed up to seven years of follow-up the lasting long-term improvements in progression-free survival. This was the longest follow-up study to treat CLL with the Bruton tyrosine kinase (BTK) inhibitor. 4

"The results of both the iLLUMINATE and the ECOG-ACRIN study show an impressive prolongation of progression-free survival for the relevant ibrutinib-based combinations compared to commonly used chemo-immunotherapies," Dr. Carol Moreno, Haematologist Consultant, Santa Creu Hospital Sant Pau, Autonomous University of Barcelona, Barcelona (Spain). "These non-chemotherapies represent progress in the way we consider caring for patients, including younger patients and those with high-risk CLL characteristics, with the potential to help overcome the conflict of interest between patient efficacy and toxicity . "

"The data provided by ASH (Free ASH Whitepaper) demonstrate the clinical benefit of ibrutinib for CLL patients across the full spectrum of treatment. The long-term data also conveys confidence in the sustainable activities for the benefit of the patients, "Dr. Catherine Taylor, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. "We continue to explore the full potential of ibrutinib as part of a comprehensive clinical development program to improve outcomes and bring about changes in the importance of blood cancer diagnosis for patients."

Ibrutinib, a first-in-class BTK inhibitor, is being developed and marketed jointly by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

Results of the randomized Phase III study of ibrutinib (PCI-32765) -based treatment versus FCR chemo-immunotherapy of untreated younger patients with CLL: A study by the ECOG-ACRIN Cancer Research Group (E1912) ( Abstract LBA -4 )

In a mean follow-up of 33.4 months, the interim analysis found 77 PFS events (progression-free survival) and 14 deaths. Ibrutinib plus rituximab significantly improved PFS events compared to FCR (hazard ratio (HR): 0.352; 95% confidence interval [CI]: 0.233-0.558; p <0.0001). The predetermined limit for progression-free life has been exceeded. Treatment with ibrutinib plus rituximab also showed improvement in overall survival (OS) (HR: 0.168, 95% CI: 0.053-0.538, p = 0.0003, predetermined superiority limit p = 0.0005). 2

In a PFS subgroup analysis, treatment with ibrutinib plus rituximab showed PFS prolongation, regardless of age, sex, ability, stage of disease or presence / absence of a cytogenetic abnormality (11q23 deletion). In the current follow-up study, treatment with ibrutinib plus rituximab also demonstrated superiority over FCR in patients without IGHV mutation (HR: 0.262, 95% CI: 0.137-0.498, p <0.0001) but without IGHV mutation (HR : 0.435, 95% CI: 0.140-0.1350, p = 0.07). 2

Grade 3/4 treatment-related adverse events were observed in 58% of ibrutinib plus rituximab-treated patients and 72% of FCR-treated patients (p = 0.0042). FCR levels were more common with grade 3 or 4 neutropenia (FCR: 44% compared to ibrutinib plus rituximab: 23%, p <0.0001) and infectious complications (FCR: 17.7% compared to ibrutinib plus rituximab: 7.1%; p <0.0001). 2

Results of the Phase III iLLUMINATE Study ( Abstract # 691 )

In a median follow-up period of 31.3 months, progression-free survival was prolonged when irrigation with ibrutinib plus obinutuzumab was evaluated by the Independent Review Committee (IRC) compared with chlorambucil plus obinutuzumab (median not reached [NR] compared to 19 HR 0.231, 95% CI: 0.145-0.367, p <0.0001) with a 77% reduction in the risk of disease progression or risk of death. 3

A superiority in progression-free survival in treatment with ibrutinib plus obinutuzumab compared with chlorambucil plus obinutuzumab was also found in the high-risk population, including those without IGHV mutation, 11q deletion, 17p deletion and TP53 mutation, respectively with an 85% reduction in the risk of disease progression or mortality (median not reached [NR] compared to 14.7 months, HR 0.154, 95% CI: 0.087-0.270, p <0.0001). 5 In addition, the IRC-assessed overall response rate (ORR) was higher for the ibrutinib plus obinutuzumab-treated patients compared to chlorambucil plus obinutuzumab (88% vs. 73%); complete remission (CR rates) / complete remission with incomplete blood repair (CRi rates) was significantly higher at 19% compared to 8%. Minimal residual disease (MRD) could not be detected in the blood or bone marrow (<10 -4using flow cytometry) in 35% of patients treated with ibrutinib plus obinutuzumab compared with 25% of those treated with chlorambucil plus obinutuzumab. The overall survival rates at 30 months were 86% for patients treated with ibrutinib plus obinutuzumab compared to 85% for chlorambucil plus obinutuzumab. 3

The most common grade 3 or higher adverse events associated with ibrutinib plus obinutuzumab compared to chlorambucil plus obinutuzumab were neutropenia (36% versus 46%), thrombocytopenia (19% vs. 10%), pneumonia (7% vs. 4%), Atrial flutter (5% versus 0%), febrile neutropenia (4% vs. 6%), anemia (4% versus 8%) and infusion-related reactions (IRR, 2% versus 8%). 5No patient had to discontinue treatment with obinutuzumab due to infusion-related reactions in patients treated with ibrutinib plus obinutuzumab compared to chlorambucil plus obinutuzumab (6%). Adverse events caused discontinuation of ibrutinib treatment in 16% of patients and discontinuation of chlorambucil treatment in 9% of patients. Adverse events caused the discontinuation of obinutuzumab in treatment with ibrutinib plus obinutuzumab (13%) and chlorambucil plus obinutuzumab (13%). In a three-year follow-up study, 70% of patients who received ibrutinib plus obinutuzumab received ibrutinib monotherapy. 3

Outcome of up to seven years follow-up in the Phase Ib / II PCYC 1102 study and its extension PCYC-1103 ( Abstract # 3133 )

Results from these studies demonstrated continued efficacy of ibrutinib in newly diagnosed and r / r CLL patients. These long-term data showed sustained PFS and overall survival rates. The estimated seven-year PFS rates were 80% in patients with newly diagnosed disease and 32% in patients with r / r disease. In particular, the administration of ibrutinib in previous treatment lines resulted in better PFS treatment results in r / r patients. 4

The overall response rate was 89% for all patients (CR, 15%), with similar rates in newly diagnosed patients (87% [CR, 32%]) and r / r-CLL patients (89% [CR, 10%] , The mean duration of response (DOR) was NR (95% CI: 0 + -85 +) in newly diagnosed CLL patients and was 57 months (95% CI: 0 + -85 +) with r / r-CLL agency counted. 6 The PFS median score was NR (95% CI: unpredictable [NE], NE) for newly diagnosed patients and was 51 months (95% CI: 37-70) for r / r CLL patients. 4.6 Overall median survival was NR in newly diagnosed patients (95% CI: 80-NE) or r / r CLL patients (95% CI: 63-NE), with estimated seven-year overall survival rates of 75% and 75%, respectively. 52%. 4

Adverse events of grade 3 or higher were reported in 74% of newly diagnosed patients and 89% of r / r patients with CLL. Hypertension (newly diagnosed, 32%, r / r, 26%), diarrhea (newly diagnosed, 16%, r / r, 4%) and hyponatraemia (newly diagnosed, 10%, r / r, 0%) were among the most common therapy-related adverse events of grade 3 or higher. Severe hemorrhage and atrial flutter, thrombocytopenia, grade 3 anemia and arthralgia were seen in 11% or less of newly diagnosed and r / r patients. In addition, infections (newly diagnosed, 23%, r / r, 55%) were more common in r / r-CLL patients. 6No or unexpected adverse events were observed and the occurrence of these events of grade 3 or greater and serious adverse events increased with time (except high blood pressure). 6

#THE END#

About the ECOG-ACRIN-E1912 study

The Phase III study (E1912) evaluated previously untreated patients with CLL aged 70 or younger who were randomly assigned to receive ibrutinib (420 mg / day to progression) and rituximab (50 mg / m) 2 on day 1 of cycle 2, 325 mg / m2 on day 2 of cycle 2, 500 mg / m2 on day 1 of cycles 3 to 7) (n = 354) or six intravenous administrations of fludarabine (25 mg / m) 2 (), and cyclophosphamide 250 mg / m 2 ) on days 1 to 3 (with rituximab 50 mg / m 2 on day 1 of cycle 1; 325 mg / m 2 on day 2 of cycle 1; 500 mg / m 2 on day 1 of cycles 2 to 6) every 28 days (n = 175). The primary endpoint was progression-free survival (PFS) and a secondary endpoint overall survival (OS). 2

The state-sponsored study was prepared by researchers in cooperation with ECOG-ACRIN. It was conducted by the National Clinical Trials Network of the NCI (National Cancer Institute). Pharmacyclics LLC provided Ibrutinib under an agreement for a research and development collaboration with the NCI and a separate agreement with ECOG-ACRIN.

About the iLLUMINATE study

iLLUMINATE ( PCYC-1130 ) evaluated patients with newly diagnosed CLL who were randomized to receive 420 mg ibrutinib once daily until disease progression or unacceptable toxicity or in combination with obinutuzumab 1000 mg intravenously for six cycles (n = 113); or chlorambucil on days 1 and 15 for each cycle plus 1000 mg of obinutuzumab administered intravenously over a period of 6 cycles (n = 116). The median age of the patients was 71 years and 65% of the patients had a high hazard potential for genomic characteristics. The primary endpoint was PFS, as assessed by the Independent Review Committee. The secondary endpoints were progression-free survival (PFS) in a high-risk population, the rate of undetectable MRD,3

About PCYC-1102 and PCYC-1103

In a follow-up study lasting up to seven years, the studies (Phase Ib / II, PCYC-1102 and their extension PCYC-1103 ) evaluated newly diagnosed and r / r-CLL patients (n = 132, newly diagnosed = 31, r / r = 101), including those with high-risk traits, who received 420 mg or 840 mg ibrutinib once daily until disease progression or unacceptable toxicity. By the cut-off date, 55% of the newly diagnosed and 21% of the r / r patients continued to receive ibrutinib with a median follow-up of 67 months. 4

About ibrutinib

Ibrutinib is a brutone tyrosine kinase (BTK) inhibitor, a first in this new class of drugs that works by building strong covalent binding with BTK, which blocks the transmission of cell survival signals to malignant B lymphocytes. 7 through blockade of the BTK protein Ibrutinib contributes to the destruction of these cancer cells and reduce their number. As a result, it slows the progression of the cancer. 8th

Ibrutinib is currently authorized in Europe for the following uses: 9

Chronic lymphocytic leukemia (CLL): As a single agent for the treatment of adult patients with previously untreated CLL and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have previously undergone at least one therapy.
Mantle Cell Lymphoma (MCL): Adult patients with relapsed or refractory mantle cell lymphoma.
Waldenstrom Macroglobulinemia (WM): Adult patients who have undergone at least one prior therapy or first-line treatment or first-line treatment of patients who are not eligible for chemo-immunotherapy.
Ibrutinib is approved in more than 90 countries and has been used to treat more than 135,000 patients around the world as part of its approved indications. 10

The most common adverse events with ibrutinib supplements include diarrhea, neutropenia, hemorrhage (eg bruises), musculoskeletal pain, nausea, rash, and pyrexia. 9

For a full list of adverse reactions and information on dosing and administration, contraindications and other precautions for use with Ibrutinib, see the Summary of Product Characteristics .

The data presented in the ASH 2018 provide evidence of the benefits of first-line treatment with IMBRUVICA ® , treatment with ibrutinib for all groups of patients with chronic lymphocytic leukemia (CLL).

On December 10, 2018 Janssen pharmaceutical companies at Johnson & Johnson reported new results from three key studies of IMBRUVICA (ibrutinib) in chronic lymphocytic leukemia (CLL), a form of difficult blood cancer treat and the most common form of leukemia in adults (Press release, Johnson & Johnson, DEC 10, 2018, View Source [SID1234531991]). 1 The findings were presented at the 60th to annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) held in San Diego (California).

The results of the phase 3 study sponsored by the National Cancer Institute (NCI) (E1912), led by the ECOG-ACRIN cancer research group, were presented during the last oral summary session. The study evaluated the combination of ibrutinib plus rituximab compared to a regimen for chemotherapy of fludarabine, cyclophosphamide, and rituximab (FCR) in patients 70 years of age or younger with CLL who had not received prior treatment. After almost three years of follow-up, the data showed that ibrutinib plus rituximab significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to the FCR combination. two

The iLLUMINATE (PCYC-1130) Phase 3 data was also presented in an oral session and simultaneously published in The Lancet Oncology . The results showed that the combination of ibrutinib plus obinutuzumab significantly improved progression-free survival versus the combination of chlorambucil and obinutuzumab in patients with newly diagnosed CLL. 3 These data recently supported the submission of a Type II variation request to the European Medicines Agency (EMA), which seeks approval to expand the use of ibrutinib in combination with obinutuzumab in adults with CLL who have not received prior treatment.

In addition, the ibrutinib data from the phase 1b / 2 study and its extension study (PCYC-1102, PCYC-1103), with up to seven years of follow-up in patients with newly diagnosed CLL and relapsed / recurrent (R / R) , showed long-term survival benefits as monotherapy, which implies the longer follow-up of a Bruton tyrosine kinase inhibitor (BTK) in CLL. 4

"The results of the iLLUMINATE and ECOG-ACRIN studies show an impressive survival without prolonged progression for the relevant combinations based on ibrutinib, compared to the regimens of chemoimmunotherapy usually used," said Dr. Carol Moreno, a hematologist at the Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona (Spain). "These non-chemotherapeutic regimens represent an advance in the way we might consider treating patients, including the youngest and those with high risk characteristics in CLL, with potential to address the compromise between efficacy and toxicity for patients. »

"The data presented in the ASH (Free ASH Whitepaper) provide more convincing evidence of the clinical benefit that ibrutinib can offer to patients across the spectrum of CLL treatment. The long-term data also offer reliability in terms of sustained activity for patients, "explained Dr. Catherine Taylor, head of the area of hematology therapy in Europe, Middle East and Africa (EMEA) of Janssen-CilagLimited. "We continue to explore the full potential of ibrutinib through a comprehensive clinical development program, in order to improve the results and change what the diagnosis of blood cancer means for patients."

JanssenBiotech, Inc. and PharmacyclicsLLC, an AbbVie company, jointly develop and market ibrutinib, a first-class BTK inhibitor.

Results of the randomized phase 3 study of ibrutinib treatment (PCI-32765) versus chemoimmunotherapy with CRF in younger patients with CLL who were not previously treated: a study by the ECOG-ACRIN cancer research group (E1912) ( summary No. LBA-4 )

With an average follow-up of 33.4 months, the provisional analysis observed 77 cases of progression-free survival and 14 deaths. The combination of ibrutinib plus rituximab significantly improved progression-free survival compared to the FCR combination (hazard ratio: 0.352, 95% confidence interval [CI]: 0.223-0.558, p <0.0001); the pre-established limit for survival without progression was crossed. The treatment group of ibrutinib plus rituximab also showed an improvement in overall survival (hazard ratio: 0.168, 95% CI: 0.053-0.538, p = 0.0003, pre-established upper limit p = 0.0005). two

In a progression-free survival subgroup analysis, the combination ibrutinib plus rituximab showed a prolonged progression-free survival independent of age, sex, functional status, disease phase or the presence / absence of cytogenetic abnormalities, 11q23 deletion. With the current follow-up, the ibrutinib plus rituximab combination was also superior to the FCR combination in patients who did not have mutations in IGHV (risk ratio: 0.262, 95% CI: 0.137-0.498, p <0.0001) but not in patients who presented mutations in IGHV (hazard ratio: 0.435, 95% CI: 0.140-0.1350, p = 0.07). two

Adverse reactions associated with grade 3/4 treatment were observed in 58% of patients treated with the combination ibrutinib plus rituximab, and in 72% of patients treated with HRG (p = 0.0042). The FCR combination was more frequently associated with grade 3 and 4 neutropenia (FCR: 44% versus the combination ibrutinib plus rituximab: 23%, p <0.0001) and infectious complications (FCR: 17.7% vs. the combination ibrutinib plus rituximab: 7.1%, p <0.0001). two

Results of the 3 phase iLLUMINATE study ( summary # 691 )

At an average follow-up of 31.3 months, the combination of ibrutinib plus obinutuzumab significantly prolonged progression-free survival as assessed by the Independent Review Committee (ICR), compared with the combination of chlorambucil and obinutuzumab (average not reached versus 19, 0 months, risk ratio 0.231, 95% CI: 0.145-0.367, p <0.0001), with a 77% reduction in the risk of progression or death. 3

High progression survival was also observed in the ibrutinib plus obinutuzumab combination group compared to the combination of chlorambucil plus obinutuzumab, even in those patients who had mutations in IGHV, del11q, del17p and / or TP53, with an 85% reduction in the risk of progression or death (average not reached versus 14.7 months, risk ratio 0.154, 95% CI: 0.087-0.270, p <0.0001). 5 In addition, the overall response rate (ORR) assessed by the IRC was higher in the ibrutinib plus obinutuzumab group compared to the chlorambucil plus obinutuzumab group (88% versus 73%); Complete response (CR) / complete response with incomplete blood recovery (CRi) rates were also higher, with 19% versus 8%, respectively. No minimal residual disease (MRE) was detected in the blood and / or spinal cord (<10 -4by flow cytometry) in 35% of patients treated with ibrutinib plus obinutuzumab, compared to 25% of patients treated with chlorambucil plus obinutuzumab. Overall survival rates at 30 months were 86% for the ibrutinib plus obinutuzumab group, versus 85% for the chlorambucil plus obinutuzumab group. 3

The most common adverse events of grade 3 or higher in the ibrutinib plus obinutuzumab group versus the chlorambucil plus obinutuzumab group were neutropenia (36% vs. 46%), thrombocytopenia (19% vs. 10%), pneumonia (7% vs. 4%), atrial fibrillation (5% vs. 0%), febrile neutropenia (4% vs. 6%), anemia (4% vs. 8%), and perfusion-related reactions (IRR, 2% vs 8%). %). 5No patient discontinued treatment with obinutuzumab due to infusion-related reactions in the ibrutinib plus obinutuzumab combination group, compared with the chlorambucil plus obinutuzumab group (6%). Adverse reactions continue to cause the interruption of ibrutinib treatment in 16% of patients and involves the interruption of chlorambucil intake in 9% of patients. Adverse reactions caused the interruption of treatment with obinutuzumab in the group of ibrutinib plus obinutuzumab (9%) and in the group of chlorambucil plus obinutuzumab (13%). With an approximate follow-up of three years, 70% of the patients in the ibrutinib plus obinutuzumab group continued on monotherapy with ibrutinib.3

Results of up to seven years of follow-up in the PCYC-1102 phase 1b / 2 study and its extension, PCYC-1103 ( abstract number 3133 )

The results of these studies demonstrated a lasting efficacy of ibrutinib in patients with recently diagnosed or relapsing / recurrent CLL. These long-term data showed sustained overall progression-free survival and response rates. The estimated 7-year progression-free survival rates were 80% for patients with newly diagnosed disease, and 32% for patients with recurrent / relapsing disease. In particular, the administration of ibrutinib in earlier lines of therapy resulted in improved progression-free survival outcomes in relapsed / recurrent patients. 4

The overall response rate was 89% for all patients (complete response, 15%) with similar rates in patients with recently diagnosed CLL (87% [complete response, 32%] and relapsed / recurrent (89% [response complete, 10%]) The average response duration (DOR) (95% CI: 0 + -85 +) was not reached in the newly diagnosed CLL patients and was 57 months (95% CI: 0+ . -85+) for CLL patients relapsed / recurrent 6 survival was not reached average progression (95% IC: not estimable [NE], NE) for CLL patients newly diagnosed was 51 months (95% CI: 37-70) for relapsed / recurrent CLL patients 4.6 The average general response was not reached in patients with recently diagnosed CLL (95% CI: 80-NE) or relapsed / recurrent (95% CI: 63-NE), with estimated overall response rates at seven years of 75% and 52%, respectively. 4

Grade 3 or higher adverse reactions were recorded in 74% of patients with recently diagnosed CLL and in 89% of relapsed / recurrent patients. Among the most common adverse reactions of grade 3 or higher that arose with treatment are hypertension (recent diagnosis, 32%, relapse / recurrent, 26%), diarrhea (recent diagnosis, 16%, relapse / recurrent, 4%) and hyponatremia (recent diagnosis, 10%; relapse / recurrent, 0%). In 11% or less of newly diagnosed or relapsed / recurrent patients, significant bleeding and grade 3 or higher articular fibrillation, thrombocytopenia, anemia, and arthralgia were detected. In addition, infections (recent diagnosis, 23%; relapse / recurrent,6 No new or unexpected adverse reactions were observed and the prevalence of most of the adverse reactions of grade 3 or higher and severe decreased with time, except hypertension. 6

#FINISH#

About the ECOG-ACRIN E1912 study

The phase 3 study (E1912) evaluated patients with CLL aged 70 years or younger who had not received previous treatment and who had been randomly assigned to receive ibrutinib (420 mg / day until disease progression) and rituximab (50 mg / m 2 on day 1 of cycle 2, 325 mg / m 2 on day 2 of cycle 2, 500 mg / m 2 on day 1 of cycles 3-7) (n = 354) or six stages of fludarabine intravenous (25 mg / m 2 ) and cyclophosphamide (250 mg / m 2 ) days 1-3 with rituximab (50 mg / m 2 on day 1 of cycle 1; 325 mg / m 2 on day 2 of cycle 1; 500 mg / m 2on day 1 of cycles 2-6) every 28 days (n = 175). The primary endpoint was survival without progression with a secondary criterion of overall survival. two

The study, financed with federal funds from the US UU., Was designed by researchers together with ECOG-ACRIN. It was conducted in the NCI national clinical trials network. PharmacyclicsLLC provided ibrutinib under a research and development cooperation agreement with the NCI and an independent agreement with ECOG-ACRIN.

About the iLLUMINATE study

iLLUMINATE ( PCYC-1130) evaluated newly diagnosed patients with CLL who were randomized to receive ibrutinib 420 mg once a day continuously until disease progression or unacceptable toxicity in combination with obinutuzumab 1000 mg intravenously for six cycles (n = 113 ); or chlorambucil on days 1 and 15 of each cycle plus obinutuzumab 1000 mg intravenously for 6 cycles (n = 116). The average age of the patients was 71 years and 65% of the patients presented high-risk genomic characteristics. The primary endpoint was survival without progression, assessed by an Independent Review Committee.3

About PCYC-1102 and PCYC-1103

With a follow-up of up to seven years, the studies (phase 1b / 2, PCYC-1102 and its extension, PCYC-1103 ) evaluated patients with newly diagnosed CLL and relapsed / recurrent (n = 132; newly diagnosed = 31; relapse / recurrent = 101), including those with high-risk characteristics, who received 420 mg or 840 mg once daily of ibrutinib until disease progression or unacceptable toxicity. At the deadline, 55% of newly diagnosed patients and 21% of relapsed / recurrent patients continued to take ibrutinib, with an average follow-up of 67 months. 4

About ibrutinib

Ibrutinib is a first-class inhibitor of Bruton’s tyrosine kinase (BTK), which works by forming a strong covalent bond with BTK to block the transmission of cellular survival signals within malignant B cells. 7 By blocking this BTK protein, ibrutinib helps eliminate and reduce the number of cancer cells, thereby delaying the progression of cancer. 8

Currently, ibrutinib is authorized in Europe for the following uses: 9

chronic lymphocytic leukemia (CLL): As a single agent for the treatment of adult patients with CLL who have not undergone previous treatment, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received less a previous treatment.
Mantle cell lymphoma (MCL): Adult patients with relapsed / recurrent MCL.
Waldenström macroglobulinemia (MW): Adult patients who have received at least one previous treatment or first-line treatment for patients not suitable for chemoimmunotherapy.
Ibrutinib is approved in more than 90 countries and, to date, it has been used to treat more than 135,000 patients worldwide for its approved indications. 10

The most common adverse reactions observed with ibrutinib are diarrhea, neutropenia, haemorrhage (eg, bruising), musculoskeletal pain, nausea, rash, and pyrexia. 9

Consult the summary of product characteristics for a complete list of side effects and information on dosing and administration, contraindications and other precautions when taking ibrutinib.

Blue Earth Diagnostics Announces U.S. Food and Drug Administration (FDA) Filing Acceptance of Supplemental New Drug Application (sNDA) for 18F-fluciclovine PET Imaging in Glioma

On December 10, 2018 Blue Earth Diagnostics, a molecular imaging diagnostics company, reported that the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental New Drug Application (sNDA) for the expanded use of Axumin (fluciclovine F 18) in adults for the detection and continuing assessment of glioma (Press release, Blue Earth Diagnostics, DEC 10, 2018, View Source [SID1234531990]).

Fluciclovine is a synthetic amino acid labeled with the radioisotope F 18, enabling PET imaging to visualize the increased amino acid transport that occurs in malignant tumors such as glioma, which is a serious and life-threatening condition accounting for about 80% of all malignant brain tumors.

18F-Fluciclovine, under the tradename Axumin (fluciclovine F 18) injection, is FDA-approved for use in positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood levels of prostate specific antigen (PSA) following prior treatment. 18F-Fluciclovine PET imaging is being investigated for the detection and continuing assessment of glioma. (For additional product information please see the end of this news release.) 18F-Fluciclovine has previously been granted Orphan Drug status by both the FDA and the European Medicines Agency for the diagnosis of glioma.

"We are very pleased that the FDA has accepted for review our sNDA submission for the use of 18F-fluciclovine PET imaging in glioma," said Jonathan Allis, D. Phil., CEO of Blue Earth Diagnostics. "Expanding the label for Axumin is part of our mission to develop and commercialize innovative PET imaging products that address unmet medical needs for patients with cancer."

"Glioma is the twelfth leading cause of death from cancer, and certain aggressive forms of the disease, such as glioblastoma multiforme, can progress rapidly," said Peter Gardiner, MB ChB, MRCP, FFPM, CMO of Blue Earth Diagnostics. "Physicians need precise information about the location and extent of the tumor to help guide surgical procedures and radiation therapy, as well as for subsequent continued assessment and monitoring of the disease. We are exploring the potential utility of 18F-fluciclovine PET to assist them in these efforts."

Blue Earth Diagnostics recently announced results from one of the Phase 3 clinical trials supporting the sNDA submission to the FDA at the Society for Neuro-Oncology annual meeting in November 2018. The study, BED006, was a prospective, blinded image evaluation that examined the diagnostic performance of 18F-fluciclovine PET imaging, in conjunction with various types of MRI, for imaging of suspected glioma when interpreted by readers unfamiliar with 18F-fluciclovine PET. Results indicated a Positive Predictive Value (PPV) of more than 90% for each of the three blinded readers and consistent image interpretation across these readers. In addition, 18F-fluciclovine PET with MRI (CE-T1W MRI) identified additional regions suspicious for glioma that MRI alone was unable to identify, which subsequent biopsies confirmed as malignant. To date, the safety profile of 18F-fluciclovine PET imaging in patients with glioma appears to be consistent with that summarized in the current Axumin U.S. prescribing information.

About 18F-fluciclovine PET in Glioma

18F-Fluciclovine PET is a diagnostic imaging radiopharmaceutical for PET imaging that consists of a synthetic amino acid labeled with the radioisotope F 18, enabling the visualization of the increased amino acid transport that occurs in malignant tumors. 18F-Fluciclovine, under the trade name Axumin, is approved by the U.S. Food and Drug Administration (FDA) for PET imaging in men with recurrent prostate cancer. The clinical trial program to support the safety and efficacy, in terms of diagnostic performance, of 18F-fluciclovine PET imaging in adults for the detection and continuing assessment of glioma encompasses four trials conducted in Japan by Nihon Medi-Physics Co., Ltd and two studies in Europe and the United States by Blue Earth Diagnostics. To date, the safety profile of 18F-fluciclovine PET imaging in patients with glioma appears to be consistent with that summarized in the current Axumin prescribing information. 18F-Fluciclovine has been granted Orphan Drug status by both the FDA and the European Medicines Agency for the diagnosis of glioma. The compound was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences.

About Glioma

Glioma, the most commonly occurring type of primary brain tumor, is a serious and life-threatening condition. Cancer of the brain and central nervous system (CNS) is the twelfth most common cause of cancer death worldwide. Glioma accounts for about 25% of all brain tumors, and 80% of all malignant brain tumors. The most aggressive form of glioma, glioblastoma multiforme, is associated with significant morbidity and mortality with relatively low 5-year survival estimates after diagnosis. Current treatment options for patients with glioma include surgery, radiation and chemotherapy. Accurate evaluation of the location and extent of a glioma tumor is essential before or during surgery and radiotherapy and in assessing the continuing status of the disease. The detection and assessment of gliomas typically involves magnetic resonance imaging (MRI), which may be complemented by metabolic imaging using an appropriate amino acid-based PET radiopharmaceutical as recommended in the Response Assessment in Neuro-Oncology (RANO) working group and European Association for Neuro-Oncology (EANO) guidelines.1

U.S. Indication and Important Safety Information About Axumin*

INDICATION

Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full U.S. Axumin prescribing information is available at www.axumin.com.

*This press release is intended to provide information about Blue Earth Diagnostics’ business in the United States. Please be aware that the approval status and product label for Axumin varies by country worldwide. Refer to the individual country product label for complete information or contact Blue Earth Diagnostics.