On December 5, 2018 Janssen pharmaceutical companies at Johnson & Johnson reported the results of the MAIA phase 3 study, which shows that the addition of daratumumab to lenalidomide and dexamethasone (Rd) significantly reduced the risk of progression of the disease or death in patients with recently diagnosed multiple myeloma who are not suitable for autologous stem cell transplantation (ASCT) ( abstract # LBA-2 ) (Press release, Johnson & Johnson, DEC 5, 2018, View Source [SID1234531914]). 1 These data were presented during the oral session of last-minute last-minute summaries at the 60th annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California.

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!

"The Phase 3 MAIA study reinforces the clinical profile of daratumumab in combination with a standard treatment regimen for newly diagnosed patients with multiple myeloma who are not eligible for transplantation," states Thierry Facon, MD, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France and principal investigator. "The positive data show the potential role of daratumumab in combination with lenalidomide and dexamethasone as a new important therapeutic approach for this patient population."

At a mean follow-up of 28 months, data from the phase 3 MAIA study showed that daratumumab in combination with Rd significantly reduced the risk of progression or death of the disease by 44 percent in newly diagnosed multiple myeloma patients who are not fit for transplantation, compared to treatment with Rd alone (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.43-0.73, p <0.0001). 1 The median progression free survival (PFS) for daratumumab-Rd has not yet been achieved, compared to 31.9 months for patients who received Rd alone. oneThe incorporation of daratumumab resulted in deeper responses with respect to Rd alone, including increased rates of complete response (CR) or higher (48 percent vs. 25 percent) and improved rates of very good partial response (VGPR) or better (79 percent, versus 53 percent). 1 Daratumumab-Rd induced a 3-fold higher rate of negativity to minimal residual disease (MRD) compared to those who received Rd alone (24 percent vs. 7 percent). one

"Estos datos subrayan el perfil clínico estable observado en los pacientes recién diagnosticados con mieloma múltiple que reciben terapia con daratumumab, incluso para aquellos que no son aptos para el trasplante", comenta la Dra. Catherine Taylor, directora del área de terapia hematológica para Europa, Oriente Medio y África (EMEA) de Janssen-Cilag Limited. "Es el tercer estudio en pacientes recientemente diagnosticados que ha alcanzado su principal criterio de evaluación y esperamos continuar proporcionando avances innovadores a pacientes con mieloma múltiple a través de nuestro robusto programa de investigación clínica, que cuenta con el potencial de revolucionar el tratamiento del cáncer atacando a la enfermedad en sus etapas más tempranas", añade Taylor.

The most common grade 3/4 adverse events arising from treatment (TEAE) for daratumumab-Rd (≥ 10 percent) included neutropenia (50 percent), lymphopenia (15 percent), pneumonia (14 percent), and anemia (12 percent). 1 Infusion-related reactions (RRI) occurred in 41 percent of patients, of whom only 3 percent were grade 3/4. 1 The incidence of invasive secondary neoplasms was 3 percent in the daratumumab-Rd group, compared to 4 percent with Rd alone. 1 TEAEs with a death result were 7 percent in the daratumumab group, compared to 6 percent in the Rd group.1 The safety profile of daratumumab was in line with that of previous studies. one

These data will support a future marketing authorization request for daratumumab in combination with Rd for this patient population.

#FINISH#

About the MAIA 1 trial

The randomized, open-label, multi-center phase 3 study included 737 newly diagnosed patients with multiple myeloma unsuitable for high-dose chemotherapy and ASCT between 45 and 90 years (mean age 73). Patients were randomly assigned to receive daratumumab-Rd or Rd only in cycles of 28 days. In the daratumumab-Rd treatment group, patients received IV daratumumab 16 milligrams per kilogram (mg / kg) weekly for cycles 1 – 2, every two weeks for cycles 3-6 and every 4 weeks for cycle 7 and later. Patients in the daratumumab-Rd and Rd treatment group received 25 mg of lenalidomide on days 1 – 21 of each 28-day cycle and dexamethasone at 40 mg once per week for each cycle.

About daratumumab

Daratumumab is a first-generation biologic drug against the CD38 antigen, a protein that is expressed at high levels on the surface of multiple myeloma tumor cells, regardless of the stage of the disease. 2 Daratumumab induces rapid death of cancer cells through multiple immunologically mediated mechanisms of action, including complementary cytotoxicity (CDC), cellular cytotoxicity by antibody dependence (ADCC), cellular phagocytosis by antibody dependence (ADCP) and apoptosis , in which a series of molecular steps in a cell leads to its death. 3 Daratumumab also reduced a subset of suppressor cells of myeloid origin (CD38 + MDSCs), CD38 + T regulatory cells (Tregs) and CD38 + B (Bregs). 3 Currently daratumumab is under study through a comprehensive clinical development program on different treatments for multiple myeloma, including parameters such as first-line treatment and relapse. 4,5,6,7,8,9,10,11 Likewise, there are additional studies in progress or planned in order to study their potential in malignant or premalignant hematological diseases in which the CD38 protein is expressed, such as latent myeloma. . 12-13 For more information, see www.clinicaltrials.gov.

In Europe, daratumumab is currently indicated for use in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for an autologous stem cell transplant, whose previous treatment included an inhibitor of the proteasome and an immunomodulatory agent, and that they would have demonstrated a progression of the disease in the last treatment and in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one previous therapy 3 . For more information on daratumumab, see the Summary of Product Characteristics inView Source .

In August 2012 , Janssen Biotech, Inc. and Genmab A / S signed a worldwide agreement that awarded Janssen an exclusive license to develop, manufacture and market daratumumab. 14

About multiple myeloma

Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells. 15 In 2016, more than 45,000 new cases were diagnosed in Europe and more than 29,000 patients died 16 . Up to half of the patients with a recent diagnosis do not reach the five-year survival rate 17 and almost 29% of the patients with MM will die within one year of diagnosis. 18

Although treatment may result in remission, unfortunately, most patients will most likely relapse as there is currently no cure. 19 Refractory multiple myeloma occurs when the disease progresses within 60 days of the last therapy. 20,21 Recurrent cancer occurs when the disease returns after a period of initial, partial or complete remission. 22 While some patients with MM have no symptoms at all, most patients are diagnosed due to symptoms that may include bone problems, low blood counts, elevated calcium, kidney problems, or infections. 2. 3 Patients who relapse after treatment with standard therapies, including PIs and immunomodulatory agents, have a poor prognosis and few treatment options are available. 24

On December 5, 2018 iCell Gene Therapeutics, LLC reported results from a study ongoing at Chengdu Military General Hospital of ICG144, the first CLL1-CD33 Compound CAR T-cell (cCAR) in clinical study, in patients with particularly difficult to treat Acute Myeloid Leukemia (AML) (Press release, iCell Gene Therapeutics, DEC 5, 2018, View Source [SID1234531930]). Patients 1 and 2 both failed multiple previous cycles of therapy and presented with complex conditions limiting further options. Treatment with CLL1-CD33 cCAR led both patients to complete response and engraftment of haploidentical stem cell transplantation (allo-HSCT) without myeloablative conditioning.

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!

"Patient response seen to date is encouraging for refractory AML patients, and opens the potential of this novel therapy as bridge to transplant, a supplement to chemotherapy, or as a standalone therapy for patients with acute myeloid leukemia." stated Dr. Fang Liu, MD, PhD, the Principal Investigator of the study who presented the results at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego. Dr. Yupo Ma, MD, PhD, Chairman of iCell Gene Therapeutics added, "Initial patient experience highlights the potential importance of iCell’s proprietary multiple antigen targeting and enhancing technologies to overcome antigen escape and improve treatment outcomes."

Upon enrollment, patients receive a lymphodepletion regimen consisting of fludarabine and cyclophasphamide followed by 1×106 – 2×106 CAR T cells/kg, nonmyeloablative conditioning and Haplo-HSCT

Patient 1 is a 6-year-old originally diagnosed with Franconi anemia transformed JMML and eventually to AML-M5 with more than 90% blasts in the marrow, complex karyotype and FLT3-ITD mutation.
Patient 2 is a 23-year-old, failed to TKIs, AP-CML (basophils>20%, plt>1000X109/L), T315I mutation.
Complete response and Haplo-HSCT engraftment was observed in both patients.
Grade 1 CRS and pancytopenia was observed in both patients.
Grade 3 neurotoxicity was observed in Patient 1.
About CLL1-CD33 cCAR T cell therapy

CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. The diseases treated by CLL1-CD33 cCAR could include acute myeloid leukemia, myelodysplastic syndromes, chronic myeloid leukemia and chronic myeloproliferative neoplasms. CLL1 is associated with leukemia stem cells and disease relapse, while CD33 is expressed on bulky AML disease. Treatment of AML is a challenge due to heterogeneity of AML bearing cells, which renders single antigen targeting CAR T-cell therapy ineffective. ICG144 cCAR is designed to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.

About AML

Acute myeloid leukemia (AML) is the abnormal proliferation of immature myeloid cells and the most common leukemia in adults. Prognosis is dismal when AML relapses or is refractory to chemotherapy. Mortality associated with this disease is high, with approximately 10,000 deaths in 2018 in the US.

On December 5, 2018 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that updated data from ongoing Phase I clinical trials of ADCT-402 (loncastuximab tesirine) and ADCT-301 (camidanlumab tesirine) in multiple subtypes of lymphoma during oral and poster presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (Press release, ADC Therapeutics, DEC 5, 2018, View Source [SID1234596070]).

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!

"We are encouraged by the safety profiles and strong single-agent anti-tumor activity we continue to observe in the 183-patient first-in-human clinical trial of ADCT-402 and the 113-patient trial of ADCT-301," said Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics. "The updated ADCT-402 data presented at ASH (Free ASH Whitepaper) support its continued evaluation in our ongoing pivotal clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma. For ADCT-301, we now have the dosing data to support further investigation in a planned pivotal Phase II trial in patients with relapsed or refractory Hodgkin lymphoma, which we look forward to initiating in 2019."

ADCT-402 Oral and Poster Presentations at ASH (Free ASH Whitepaper)

Interim Results from the First-in-Human Clinical Trial of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (Abstract 398)

Oral presentation: John Radford, MD, FRCP, Manchester Academic Health Centre, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK

Data were presented from a subpopulation of 139 evaluable patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who had failed or were intolerant to established therapies. The patients had a median age of 63 years and had received a median of three previous therapies. Patients received doses of ADCT-402 ranging from 15 to 200 μg/kg every three weeks. The median number of cycles received was two and the median duration of treatment was 43 days.

Key findings from the oral presentation include:

ADCT-402 has demonstrated manageable toxicity in patients with R/R DLBCL
At doses >120 μg/kg, the overall response rate (ORR) was 43.3% (55/127 patients with DLBCL), comprising 23.6% complete responses and 19.7% partial responses
At doses >120 μg/kg, after a median follow up of 5.5 months, median duration of response (DoR) was not reached in patients achieving a complete response
A pivotal Phase II study is currently enrolling patients with R/R DLBCL to evaluate the efficacy and safety of ADCT-402 at dose 150 μg/kg every three weeks for two cycles followed by dose 75 μg/kg every three weeks (NCT03589469).

Safety and Efficacy of ADCT-402 (Loncastuximab Tesirine), a Novel Antibody Drug Conjugate, in Relapsed/Refractory Follicular Lymphoma and Mantle Cell Lymphoma: Interim Results from the Phase I First-in-Human Study (Abstract 2874)

Poster presentation: Paolo Caimi, MD, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH

Data were presented from a subgroup of 29 patients, including 14 patients with follicular lymphoma (FL) and 15 patients with mantle cell lymphoma (MCL). The median age of the FL patients was 60.5 years and the median age of the MCL patients was 64 years. Patients received infusions every three weeks at doses ranging from 15 to 200 μg/kg. Patients with FL and MCL received a median of three and two cycles of ADCT-402, respectively.

Key findings from the poster presentation include:

ADCT-402 has demonstrated manageable toxicity in patients with R/R FL and R/R MCL
In patients with FL, ORR was 78.6% (11/14) and median DoR was not reached after a median follow-up time of 11.6 months
In patients with MCL, ORR was 46.7% (7/15) and median DoR was not reached after a median follow-up time of 8.7 months
ADCT-301 Oral and Poster Presentations at ASH (Free ASH Whitepaper)

Phase I Study of ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Classical Hodgkin Lymphoma (Abstract 928)

Oral presentation: Mehdi Hamadani, MD, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI

Data were presented from 67 evaluable, heavily pretreated patients with relapsed/refractory (R/R) classical Hodgkin Lymphoma (HL) who had failed or were intolerant to any established therapy known to provide clinical benefit. The median age of the patients was 38 years and they had received a median of five prior therapies. Patients were treated with doses of ADCT-301 ranging from 5 to 300 μg/kg. They completed a median of three cycles of treatment and median treatment duration was 43 days.

Key findings from the oral presentation include:

ADCT-301 has demonstrated manageable toxicity in patients with R/R HL
The most common Grade 3 or 4 treatment-emergent adverse events occurring in at least 5 percent of patients, regardless of attribution, at the 45 μg/kg dose in 37 patients were: maculopapular rash (18.9 percent),elevated gamma-glutamyltransferase (8.1 percent), elevated alanine aminotransferase (8.1 percent), elevated aspartate aminotransferase (2.7 percent), anemia (8.1 percent), Guillain-Barré syndrome / radiculopathy (8.1 percent) and increased lipase (8.1 percent)
In patients with R/R HL, therapy with ADCT-301 achieved an overall response rate (ORR) of 86.5% and a complete response rate of 43% in the 37 patients in the 45 μg/kg dose group who had received and failed prior brentuximab vedotin and most of whom had failed prior checkpoint inhibitor treatment
These data support further investigation of the 45 μg/kg dose of ADCT-301 in a planned pivotal Phase II study anticipated to commence in 2019
ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based CD25-Targeting Antibody Drug Conjugate, in a Phase I Study of Relapsed/Refractory Non-Hodgkin Lymphoma Shows Activity in T-Cell Lymphoma (Abstract 1658)

Poster presentation: Graham P. Collins, MB, BS, DPhil, Oxford University Hospitals, NHS Trust, Oxford, UK

Data were presented from 44 patients with R/R non-Hodgkin lymphoma (NHL) with a median age of 65.5 years who had received a median number of four previous systemic therapies (including prior stem cell transplant). Of those, 22 patients were in a T-cell lymphoma subgroup. Patients were treated with doses of ADCT-301 ranging from 3 to 150 μg/kg and received a median number of two cycles. Median treatment duration was 22 days.

Key findings from the poster presentation include:

ADCT-301 demonstrated an acceptable safety profile during dose-escalation
Overall, in patients with R/R NHL, therapy with ADCT-301 achieved an ORR of 31.7% (13/41) at doses >60 μg/kg
In the R/R T-cell lymphoma subgroup, therapy with ADCT-301 achieved an ORR of 53.8% (7/13) in the 60 and 80 μg/kg dose groups
These data support further investigation of ADCT-301 in T-cell lymphoma
About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (NCT03589469). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.

About ADCT-301

ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. The intra-tumor release of its PBD warhead may cause bystander killing of neighboring tumor cells. In addition, the PBD warhead will trigger immunogenic cell death, which in turn will strengthen the immune response against tumor cells. ADCT-301 is being evaluated in ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235), as well as a Phase Ib clinical trial in solid tumors (NCT03621982).

On December 5, 2018 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immunotherapies derived from its Immulytic platform, reported that Robert Coffin, Ph.D., Chief Executive Officer and Director of Replimune, will present at the BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference on Wednesday, December 12, 2018 at 2:40 PM ET at the Mandarin Oriental Hotel in New York, NY (Press release, Replimune, DEC 5, 2018, View Source [SID1234531896]).

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!

On December 5, 2018 Transgene (Paris:TNG) reported that Management will participate in the upcoming investor events set out below (Press release, Transgene, DEC 5, 2018, View Source [SID1234531915]).

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!

Transgene will meet institutional investors at the LifeSci Advisors Corporate Access Event from January 7 to 9, 2019, in San Francisco, USA, concurrent with the J.P. Morgan Healthcare conference.

The Company will also attend:

Oddo Forum: January 10 & 11, 2019 – Lyon, France
Biomed Event: January 22, 2019 – Paris, France
Degroof Petercam Healthcare Seminar: January 31, 2019 – Brussels, Belgium
HC Wainwright Conference: April 8 & 9, 2019 – London, UK
Kempen Life Sciences Conference: April 16 & 17, 2019 – Amsterdam, Netherlands
Small Cap Event: April 16 & 17, 2019 – Paris, France