On December 3, 2018 Celgene Corporation (NASDAQ:CELG) reported initial safety data from its ongoing proof-of-concept trial of JCARH125 in patients with relapsed/refractory multiple myeloma. JCARH125 is an investigational BCMA-targeting CAR T cell therapy being developed by Juno Therapeutics, A Celgene Company (Press release, Celgene, DEC 3, 2018, View Source [SID1234531848]). Results were presented by Sham Mailankody, MBBS, in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA (Abstract #957).

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 data reported from the multicenter, phase 1/2 EVOLVE trial includes patients who have been treated with JCARH125 in the dose escalation study. The primary objectives of the phase 1 portion of the trial are safety and identification of a recommended phase 2 dose. The patients enrolled in the study had to have received at least three prior lines of multiple myeloma therapy, including an autologous stem cell transplant for transplant eligible patients, a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Dose escalation is currently ongoing.

"We believe that cellular therapies targeting BCMA will play an important role in the future treatment of patients with multiple myeloma," said Mark Gilbert, M.D., Chief Medical Officer for Juno Therapeutics, A Celgene Company. "These data from 44 patients in the EVOLVE trial further support our commitment to innovation in multiple myeloma clinical research."

At data cut off, 44 patients have been infused with JCARH125 in three dose escalation cohorts. These patients were heavily pretreated, with a median of seven prior lines of therapies (range, 3-23), and 77% had high-risk cytogenetics. Seventy-one percent of patients experienced grade 1 and 2 cytokine release syndrome (CRS) with 9% of patients experiencing grade 3/4 CRS. In addition, 18% of patients experienced grade 1 and 2 neurological events with 7% of patients experiencing a grade 3/4 event. Other frequent grade 3/4 AEs included neutropenia (86%), anemia (50%), thrombocytopenia (43%) and infection (14%).

In this first report of JCARH125 data, the median follow up was only 11 weeks, yet among infused patients, the overall response rate (ORR) was 82%. At the lowest dose level of 50×106 CAR T cells, the ORR was 79% and 43% of patients achieved stringent complete response (sCR) or complete response (CR).

JCARH125 is investigational and has not been approved in any country

On December 3, 2018 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that Professor Paul G. Richardson presented updated interim data with melflufen (Ygalo) from the ongoing HORIZON trial at the 60th ASH (Free ASH Whitepaper) meeting in San Diego, California, USA (Press release, Oncopeptides, DEC 3, 2018, View Source [SID1234531865]).

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!

Overall conclusions

The updated phase II data with melflufen in late-stage relapsed-refractory multiple myeloma patients refractory to pomalidomide and/or daratumumab after failing on immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) shows:

An Overall Response Rate (ORR) of 33%, in patients where 46% had received 3+ regimens of treatments over the last 12 months
A vast majority of patients, 84%, achieved disease stabilization (SD or better)
The first evaluation of Progression Free Survival (PFS) shows a median of 4.0 months in the ongoing trial with a median of 6.4 months for responding patients
Activity was observed regardless of underlying refractory status and the traditional prognostic factor albumin was a strong predictor of ORR
The treatment was well tolerated with mainly reversible and manageable hematological adverse events. The incidence of non-hematological toxicity was low
Professor Paul G. Richardson comments

"Over the last decade, initial treatments in myeloma have been radically improved, and in particular with the advent of the widespread adoption of novel agent combination approaches as well as continuous therapy. However, the number of patients who become resistant to immunomodulatory agents, proteasome inhibitors and anti-CD38 monoclonal antibodies is increasing, and there is thus a clear need for effective treatment options with new mechanisms of action. Melflufen is a first in class peptidase-enhanced compound that does not share resistance pathways seen with currently used treatments and has general manageable toxicity with favorable tolerability. Melflufen is showing considerable promise in the relapsed and refractory setting, with clinical development ongoing" said Paul Richardson MD, the RJ Corman Professor of Medicine at Harvard Medical School and Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, USA.

About the HORIZON study

Patient recruitment to the study is ongoing. The interim data presented at the ASH (Free ASH Whitepaper) meeting is based on a data cut-off dated October 22ed 2018 with 83 patients treated and 82 patients included in the response analysis. The patients in the study are refractory to pomalidomide and/or daratumumab after failing on IMiDs and PIs.

Summary of the HORIZON interim data

The study continues to develop positively in this heavily pretreated patient group that is refractory to pomalidomide and/or daratumumab after failing on IMiDs and PIs with few remaining treatment options.

61% of patients in the study had high-risk cytogenetics, 36% of patients were ISS stage III, the median number of prior lines of therapy was 5 and the median time since initial diagnosis was 6.5 years.
All patients in the study were investigator assessed as non-responsive or non-tolerant to IMiDs and PIs, 100% of patients were also refractory to pomalidomide or daratumumab, 60% were refractory to IMiDs, PIs and anti-CD38, 55% were alkylator refractory and 93% had disease progression on or within 60 days of completion of the last therapy.
Analysis of the preliminary efficacy results showed an ORR of 32,9% and that 84,1% of the patients achieved disease stabilization (SD or better).
Overall response rate (N=82)
ORR sCR VGPR PR MR SD PD NE
total, N=82 32,9% 1,2% 11% 20,7% 6,1% 45,1% 14,6% 1,2%
Subgroup analysis suggests that response does not vary across refractory subsets but rather with the underlying disease and health status of the patient (confirming the observation made in Oncopeptides phase II study O-12-M1).
This study confirms earlier results from the O-12-M1 study in a more resistant patient population. The efficacy results in this interim analysis are encouraging with an ORR of 32,9%.

Melflufen showed a manageable safety and tolerability profile. Treatment-related grade 3/4 AEs were reported in 62 (75%) patients with the majority being hematological. Treatment-related non-hematological grade 3/4 AEs were rare with infections in only 7% of patients. 13% of the patients discontinued treatment due to AEs.

About melflufen

Melflufen (Ygalo), a peptide conjugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action. Aminopeptidases are enzymes found in all cells but are over-expressed in several cancers including MM. Melflufen selectively targets MM cells through aminopeptidase-driven accumulation. In vitro experiments show a 50-fold enrichment of the active substance in MM cells compared with administration of equal amount of an alkylator not enriched by aminopeptidases. The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.

Melflufen in clinical development

Melflufen (Ygalo) has been used to treat late-stage RRMM patients in both phase I and phase II clinical studies (O-12-M1) with favorable results. Currently, melflufen is being studied in four clinical trials for the treatment of multiple myeloma. The current studies are OCEAN, HORIZON, ANCHOR and BRIDGE.

The current clinical study program is intended to demonstrate better results from treatment with melflufen compared to established alternative drugs for patients with late-stage multiple myeloma. Melflufen could potentially provide physicians with a new treatment option for patients suffering from this serious disease.

Melflufen has been investigated in the treatment of late-stage relapsed refractory multiple myeloma (RRMM) patients. This was done in the clinical study O-12-M1 where strong final results were reported in December 2017. Currently, four clinical studies are ongoing with melflufen.

OCEAN is Oncopeptides´ pivotal Phase III study where melflufen is compared directly with current standard of care, pomalidomide, in late-stage RRMM patients.

HORIZON is a Phase II study that studies the effect of melflufen in late-stage RRMM patients with few or no remaining established treatment options. Updated interim data from this study were presented at ASH (Free ASH Whitepaper) in December 2018.

ANCHOR is a phase I/II study where melflufen is administered in combination with either bortezomib or daratumumab in RRMM patients. The results of this study aim to create understanding and knowledge among treating physicians for how melflufen can be used in combination with these drugs. In addition, the results could open up for the use of melflufen in earlier lines of treatment. The first interim data from the study was presented in a poster presentation on December 1, 2018 at ASH (Free ASH Whitepaper).

BRIDGE is a phase II study, where melflufen is used in RRMM patients with impaired renal function. This is a positioning study to show melflufen’s treatment profile in these patients.

On December 3, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported results presented by collaborators at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. One study presents details of a next-generation CAR T technology that increases T cell persistence and decreases T cell exhaustion (Press release, Atara Biotherapeutics, DEC 3, 2018, View Source [SID1234531881]). Another important study presents positive Phase 2 clinical results in patients with EBV+ PTLD involving the CNS. PTLD patient treatment patterns and health outcomes are described in additional ASH (Free ASH Whitepaper) presentations.

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!

"Our highlighted ASH (Free ASH Whitepaper) presentations this year demonstrate the promise of Atara’s next-generation CAR T and off-the-shelf, allogeneic T-cell immunotherapy pipeline," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Cutting-edge CAR T discoveries by our Moffitt Cancer Center collaborators may have wide applications including as a component of our CAR T programs in acute myeloid leukemia (AML) and B-cell malignancies. Our collaborating investigators at Memorial Sloan Kettering also showed promising Phase 2 clinical results for patients with EBV+ PTLD involving the CNS, a difficult-to-treat and often lethal complication of bone marrow and organ transplantation. We are encouraged by these robust results and the broad potential of our CAR T technologies and T cell immunotherapy platform."

60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting Summary:

Abstract 966: Mutation of the CD28 Costimulatory Domain Confers Increased CAR T Cell Persistence and Decreased Exhaustion
Session: 703. Adoptive Immunotherapy: Preclinical Studies to Improve Safety and Efficacy of CAR-T Cells
Oral Presentation Date and Time: Monday, December 3, 2018 at 5:45 pm PST
Location: Marriott Marquis San Diego Marina, San Diego Ballroom B
Authors: Justin C Boucher, Gongbo Li, Bishwas Shrestha, Maria L Cabral, Dylan Morrissey, Lawrence Guan, Marco L Davila
Affiliations:Moffitt Cancer Center

Abstract 4590: Adoptive Therapy with EBV-Specific T Cells for Treatment of CNS EBV Post-Transplant Lymphoproliferative Disease Arising after Hematopoietic Stem Cell Transplant or Solid Organ Transplant
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Susan Prockop, MD, Stephanie Suser, Ekaterina Doubrovina, MD, PhD, Hugo R. Castro-Malaspina, MD, Esperanza B. Papadopoulos, MD, James W. Young, MD, Victoria Szenes, PNP, Alison Slocum, MA, Karim Baroudy, MS and Richard J. O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center
Overview:

This poster presentation evaluated EBV-specific T-cells generated from primary and third party (tab-cel) donors.
Patients with EBV+ PTLD involving the CNS following allogeneic hematopoietic stem cell transplant (HCT) or solid organ transplant (SOT) who failed prior rituximab from the Phase 2 studies 95-024 (NCT00002663) and 11-130 (NCT01498484) were included in the analysis.
Abstract 4777: Treatment Patterns for Patients with Post-Transplant Lymphoproliferative Disorder Who Fail Rituximab after Allogeneic Hematopoietic Stem Cell Transplantation: Findings from a Systematic Literature Review
Session: 902. Health Services Research—Malignant Diseases: Poster III
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Hairong Xu, MD, PhD, Crystal Watson, MS, Shan Ashton Garib, MA, Anna Forsythe, PharmD, MSc, MBA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 3556: Estimating Long-Term Survival in a Cohort of Allogeneic Hematopoietic Stem Cell Transplant Patients
Session: 902. Health Services Research—Malignant Diseases: Poster II
Poster Presentation Date & Time: Sunday, December 2, 2018 from 6:00 pm – 8:00 pm PST
Location:San Diego Convention Center, Hall GH
Authors: Stephen Palmer, MSc, Casey Quinn, PhD, MPhil, Crystal Watson, MS and Arie Barlev, PharmD
Affiliations:Centre for Health Economics, University of York, PRMA Consulting Ltd., Atara Biotherapeutics

Abstract 4596: Dual-Sensitized T-Cells Responding to EBV Blcl and Either CMVpp65 or WT-1 Peptide Pools Have Distinct or Shared HLA Restrictions That May Depend on the Presenting HLA Alleles
Session: 723. Clinical Allogeneic and Autologous Transplantation
Poster Presentation Date & Time: Monday, December 3, 2018 from 6:00 pm – 8:00 pm PST
Location: San Diego Convention Center, Hall GH
Authors: Ekaterina Doubrovina, MD, PhD, Aisha N. Hasan, MD, Susan Prockop, MD, Karim Baroudy, MS, and Richard O’Reilly, MD
Affiliations: Memorial Sloan Kettering Cancer Center

Abstract 5839: A Systematic Literature Review of Real-World Evidence in Post-Transplant Lymphoproliferative Disorder
Authors: Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Arie Barlev, PharmD, Nazia Rashid, PharmD and Crystal Watson, MS
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5841: Younger Patients Are Impacted By Post-Transplant Lymphoproliferative Disorder: Findings from a Systematic Literature Review of Real-World Evidence
Authors: Crystal Watson, MS, Hairong Xu, MD, PhD, Anna Forsythe, PharmD, MSc, MBA, Shan Ashton Garib, MA and Arie Barlev, PharmD
Affiliations:Atara Biotherapeutics, Purple Squirrel Economics

Abstract 5840: Risk of Patients Developing Post-Transplant Lymphoproliferative Disorder within the First Year after an Allogeneic Hemopoietic Stem Cell Transplant, 2011 to 2016: A US Claims Database Analysis
Authors: Arie Barlev, PharmD, Hairong Xu, MD, PhD, Nicole Fulcher, MA, Crystal Watson, MS, Ila Sruti, MPH and Akshay Sudhindra, MD
Affiliations:Atara Biotherapeutics, IBM Watson Health

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) represents a life-threatening condition. The expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16-56 days. In EBV+ PTLD following SOT, patients failing rituximab are considered to have increased risk for chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is estimated to be 36% and 0%, respectively.

About tab-cel (tabelecleucel)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, the FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC.

On December 3, 2018 Under this agreement, Biotecnol reported that divested from it’s immuno-oncology pipeline and respective technologies (including Tb535H, and Trisoma (Press release, Biotecnol, DEC 3, 2018, View Source [SID1234570279]). Chiome will continue research and clinical development for Tb535H. In addition, Chiome will continue generating new immune-oncology products using Biotecnol’s Trisoma technology. Financial details were not disclosed.

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!

About Tb535H

Tb535H is a T-cell engager, trispecific antibody, directed against the 5T4/WAIF1 tumour antigen, a protein found on many different solid tumours and is thought to contribute to the spread of cancer cells. Tb535H recruits the patient’s T-cells –killer cells of the immune-system – and directs them to attack tumours. This highly targeted approach uses the patient’s own immune system to fight cancer. The WAIF1 antigen was discovered by scientists at the Cancer Research UK Manchester Institute. It could be a valuable target in many different cancer types, but the initial focus in this trial will be to treat cancers with high unmet-need. This includes thoracic cancers such as mesothelioma, small-cell lung carcinoma (SCLC) and non-small cell lung cancer (NSCLC), for which survival remains very low, and renal cell carcinoma.

About Trisoma technology

The Trisoma technology enables the generation of multi-specific antibody products. This unique technology overcomes the key shortcomings of conventional mono- as well as of currently developed bi-specific antibody formats. With the Trisoma technology, Biotecnol can engineer and assemble recombinant antibodies in a rational manner in order to design a chosen mechanism of action to address the killing of a specific tumour type.

On December 3, 2018 Shenzhen Salubris Pharmaceuticals Co. Ltd. (Salubris, SZSE: 002294) and Viracta Therapeutics, Inc. reported the initial closing of a financing, with Salubris committing $10 million as the lead investor (Press release, Viracta Therapeutics, DEC 3, 2018, View Source [SID1234534657]). New investor Virtus Inspire Ventures, as well as Viracta’s existing investors, NantKwest, Inc., Latterell Venture Partners and Forward Ventures, all participated in the financing. In addition to the financing, Salubris and Viracta have entered into an exclusive Collaboration and License Agreement to bring Viracta’s novel treatment approach for virus-associated malignancies to China.

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!

Viracta is advancing its innovative approach for viral-associated cancers in a Phase 1b/2 clinical trial for Epstein Barr Virus (EBV)-associated lymphomas in the US and Brazil. The approach is the first targeted, orally administered therapy for EBV-associated malignancies. It incorporates Viracta’s proprietary drug candidate, nanatinostat (VRx-3996) in combination with an antiviral as a targeted treatment to eradicate a range of viral-associated cancers. Viracta plans to initiate a clinical trial for the treatment of EBV-associated solid tumors in the coming year.

EBV-associated nasopharyngeal carcinoma is endemic in Southern China. EBV is also highly associated with the incidence and progression of other solid tumors, including gastric carcinoma, as well as NK/T cell lymphomas found throughout China. Salubris CEO, Kevin Ye highlighted, "EBV-driven cancers disproportionately impact patients in China. We look forward to partnering with Viracta to develop this new treatment option in China. The approach holds the potential to provide a valuable new treatment option for these patients, who currently still face considerable morbidity and mortality."

"We are committed to bringing our treatment approach to cancer patients around the world," commented Viracta CEO, Ivor Royston, MD. "We look forward to developing nanatinostat in collaboration with Salubris to address these major healthcare needs in China."

Under the terms of the license agreement, in addition to the equity investment made by Salubris, Viracta is eligible to receive up to $58 million in pre-commercial milestones as well as significant sales level-triggered commercial milestones and tiered royalties on sales. The Companies will collaborate for clinical development of the treatment approach for viral-associated cancers with Salubris taking on responsibility for development within the Peoples Republic of China (excluding Hong Kong, Macau and Taiwan). Viracta retains development responsibility as well as commercial rights outside of China.