First Clinical Data for REGN5458 (BCMAxCD3) Show Positive Preliminary Results in Multiple Myeloma

On December 8, 2019 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported initial clinical data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with relapsed or refractory (R/R) multiple myeloma (Press release, Regeneron, DEC 8, 2019, View Source [SID1234552066]). BCMA (B-cell maturation antigen) is a protein that is typically over-expressed on multiple myeloma cells. REGN5458 is designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells, bridging them together and activating T-cell killing of the cancer cell.

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Results were presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from the first two dose groups (3 mg and 6 mg weekly doses). Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment. Responses were observed in 4 of 7 (57%) patients, including 3 of 4 (75%) in the 6 mg dose group. In the 6 mg dose group, 2 patients (50%) were also minimal residual disease (MRD) negative, meaning that no cancer cells were detectable in their bone marrow.

"We are encouraged to see promising, rapid clinical activity even at the initial two doses of REGN5458 in heavily pretreated patients with multiple myeloma. Two patients achieved the high bar of MRD negativity, and another patient attained a very good partial response despite entering the trial with difficult-to-treat plasmacytomas outside of the bone marrow," said Israel Lowy, M.D., Ph.D., Senior Vice President and Head of Clinical and Translational Sciences for Oncology at Regeneron. "We are actively recruiting patients into higher dose groups in this trial and look forward to sharing further results in 2020. In addition, we have also initiated a clinical trial for our second BCMAxCD3 bispecific, REGN5459, which has different binding characteristics."

REGN5458 and REGN5459 were invented using Regeneron’s next generation VelocImmune "human antibody mouse" technology, together with its VelociBi platform. These allow for the creation of bispecific antibodies that closely resemble natural human antibodies with no linkers or artificial sequences. Additionally, Regeneron bispecifics are manufactured using similar approaches used for human antibody medicines, with similar pharmacokinetics.

As of data cutoff, there have been no neurotoxicity, dose-limiting toxicities or treatment discontinuations due to adverse events (AEs). The most common treatment-emergent AEs were lymphopenia (n=5), anemia (n=4) and thrombocytopenia and cytokine release syndrome (n=3 each). Grade 3 or higher treatment-emergent AEs were seen in 5 patients and included lymphopenia (n=3), hypertension (n=2) and anemia, atrial fibrillation, fatigue, febrile neutropenia, pain in extremity, septic shock and thrombocytopenia (n=1 each).

Multiple myeloma is the second most common blood cancer, with approximately 32,000 and 138,500 new diagnoses in the U.S. and world respectively. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Recent advances, such as CD38 antibody treatment, have increased life expectancy of patients from 3-4 years to 7-8 years. Despite this, multiple myeloma remains incurable, and most patients will experience relapse and require additional therapy.

The REGN5458 data follow other positive results from Regeneron’s growing bispecific pipeline, including updated REGN1979 data that will be presented at ASH (Free ASH Whitepaper). REGN1979 is an investigational CD3 bispecific that is being studied in R/R follicular lymphoma and diffuse large B-cell lymphoma, including in patients whose cancer did not respond to CAR-T therapy. Regeneron has also invented a second class of CD28 bispecifics, called co-stimulatory bispecifics, which have recently entered clinical trials.

About the REGN5458 Phase 1/2 Dose-escalation Trial
REGN5458 monotherapy is being investigated in an open-label, Phase 1/2 dose-escalation trial in patients with R/R multiple myeloma who have exhausted all therapeutic options, including proteasome inhibitors, immunomodulatory drugs and CD38 antibody treatments. The Phase 1 portion is assessing safety, tolerability and dose-limiting toxicities. Beyond the initial dose groups presented at ASH (Free ASH Whitepaper), additional dose groups are being evaluated to determine a recommended Phase 2 dose regimen. The Phase 2 portion will further assess REGN5458 anti-tumor activity and safety.

Among the patients being enrolled are those with heavily pre-treated multiple myeloma, including those with extra-medullary (outside of the bone marrow) and non-secretory disease (do not secrete detectable myeloma proteins).

In multiple myeloma clinical trials, treatment effectiveness is typically assessed by overall response rate (ORR; with response types categorized by the level of reduction in myeloma protein) and the rate of conversion to negative MRD (which measures the eradication of myeloma cells in bone marrow). For ORR, myeloma protein levels in the blood are reduced by more than 50% in partial responses (PR) and 90% in very good PR (VGPR), while complete responses are defined as no evidence of myeloma protein and ≤5% of plasma cells in the bone marrow. MRD is measured separately from ORR, and MRD negativity is defined as the absence of myeloma cells within 100,000 bone marrow cells.

About the Regeneron Bispecific Antibody Platform
All of Regeneron’s bispecific antibodies are designed to closely resemble natural human antibodies. They are derived from a next-generation version of Regeneron’s proprietary VelocImmune technology and created using the company’s VelociBi platform.

There are six Regeneron investigational bispecific antibodies currently in ongoing clinical trials for multiple blood cancers and solid tumors. These bispecifics fall into three categories:

— CD3 bispecifics are designed to bridge T-cells and tumor cells. At the tumor site, they activate T-cells via their CD3 receptors and promote T-cell killing of the cancer cells. Investigational candidates include:

CD20xCD3 (REGN1979) for non-Hodgkin B-cell lymphomas;
Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple myeloma;
MUC16xCD3 (REGN4018) for ovarian cancer.
— CD28 costimulatory bispecifics are also designed to bridge T-cells and tumor cells. At the tumor site, they costimulate T-cells via their CD28 receptors and may synergize with PD-1 inhibitors and/or CD3 bispecifics. Investigational candidates include:

PSMAxCD28 (REGN5678) in combination with Libtayo (cemiplimab) for prostate cancer.
— Tumor-targeted bispecifics are designed to target proteins only on the cancer cell. In this way, they may affect various signaling pathways to hamper the cancer cells’ ability to survive and proliferate. Investigational candidates include:

METxMET (REGN5093) for non-small cell lung cancer that is driven by MET mutations and/or amplifications. REGN5093 targets two different parts of the MET receptor on cancer cells to degrade the receptor and block its ability to trigger cell proliferation.
Regulatory Status of Oncology Programs
REGN1979, REGN5458, REGN5459, REGN4018, REGN5678, REGN5093 and Libtayo are currently under clinical development for the diseases noted in this press release, and their safety and efficacy have not been evaluated by any regulatory authority for these diseases. As part of a global collaboration agreement, Regeneron and Sanofi are jointly developing Libtayo, as well as Regeneron’s BCMAxCD3 and MUC16xCD3 bispecific programs.

Libtayo is approved in the U.S. for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation, and in other countries for similar indications. In the U.S., the generic name for Libtayo is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

Viracta Announces Positive Phase 1b/2 Data Presented at Oral Presentation on Lead Program for Epstein-Barr Virus (EBV)-associated Relapsed/Refractory Lymphomas at the 2019 American Society of Hematology (ASH) Annual Meeting

On December 8, 2019 Viracta Therapeutics, Inc. (the "Company"), a precision oncology company targeting virus-associated malignancies, reported that its lead investigator, Dr. Pierluigi Porcu of the Sidney Kimmel Cancer Center, Thomas Jefferson University, presented new clinical data from the Company’s Phase 1b/2a clinical trial of the orally administered combination of nanatinostat (Nstat) in combination with the antiviral valganciclovir for the treatment of EBV-associated relapsed/refractory lymphomas (Press release, Viracta Therapeutics, DEC 8, 2019, View Source [SID1234552065]). The data were presented during an oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting in Orlando, Florida.

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The Phase 1b/2a clinical study [NCT03397706] evaluated the combination across three cohorts. Responses were observed across all doses, and in multiple subtypes of lymphomas, including B-cell, T-cell, NK/T-cell and Hodgkin Lymphoma. The recommended Phase 2 dose of the combination was determined, which enabled the Company to proceed with the Phase 2a dose expansion portion of the study. The overall response rate (ORR) in the Phase 1b portion of the study was 56% (10/18), with 28% (5/18) complete response (CR) and a clinical benefit rate (CBR), the sum of ORR plus stable disease rate, of 78% (14/18), with a median duration of treatment for responders of 6.5 months. Two responders remained on treatment for over 12 months, including one patient who remains in complete response at 17 months, following 12.7 months on treatment. In HIV-negative patients, the ORR was 67% (10/15), with a 33% (5/15) CR and a CBR of 93% (14/15).

The combination regimen was well-tolerated, and the most common serious adverse events were hematologic and resolved without sequalae or bleeding events. Notably, no patients discontinued therapy due to a treatment-related adverse event. In the safety data set, the most frequent treatment related grade 3-4 adverse events prior to establishing a recommended Phase 2 dose (RP2D) were thrombocytopenia 25%, neutropenia 20%, and anemia 10%. All patients dosed at the RP2D including additional Phase 2a patients, had an improved hematologic Grade 3-4 safety profile, with low rates of neutropenia (8%) and anemia (8%) and no thrombocytopenia.

"There is a clear unmet medical need for effective and well-tolerated treatment options for EBV-positive lymphomas, and EBV positivity is very often correlated with poor prognosis. The overall objective response rate, complete response rate, and clinical benefit rate observed for heavily pretreated relapsed/refractory EBV-positive lymphoma patients in this dose ranging Phase 1b study are very encouraging, and represent the first reported evidence of substantial clinical efficacy for an EBV-targeting drug combination in EBV-positive lymphomas," said Pierluigi Porcu, MD, Director, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, and Professor of Medical Oncology, Dermatology, and Cutaneous Biology, at the Sidney Kimmel Cancer Center – Jefferson Health (SKCC). "The Phase 1b portion of the study also established a recommended Phase 2 dose and schedule, which is associated with a very low rate of Grade 3/4 adverse events. Preliminary results from the ongoing Phase 2 dose expansion appear to be consistent with those observed in the intermittent dose cohort of the Phase 1b study."

"These data underscore the potential for Nstat and valganciclovir as a novel therapeutic approach for the treatment of relapsed/refractory EBV-positive lymphomas. Moreover, while a biomarker diagnostic test for EBV already exists, it has not been routinely used, given the absence of an effective targeted therapy for EBV-positive lymphomas. Our goal is that our therapy will lead to increased screening of relapsed/refractory lymphomas for the presence of EBV," said Ivor Royston, MD, President and Chief Executive Officer of Viracta. "We expect to complete the Phase 2 portion of the Phase 1b/2 study in the first half of 2020, initiate a registration study in the second half of the year, and expand our treatment approach into EBV-positive solid tumor indications."

Details of the ASH (Free ASH Whitepaper) presentation are as follows:

Title: Combination of Oral Nanatinostat (Nstat), a Novel Histone Deacetylase Inhibitor (HDACi), and the Oral Anti-Viral, Valganciclovir (VGCV), Is Active in Relapsed/Refractory (R/R) Epstein-Barr Virus (EBV)-Positive B-Cell, T-Cell, and Hodgkin Lymphoma: Interim Safety and Efficacy Results from a Phase 1b/2a Study (Abstract # 465)
Presenter: Pierluigi Porcu, MD, Thomas Jefferson University
Session: Hodgkin Lymphoma and T/NK Cell Lymphoma – Clinical Studies: Novel Therapies in Peripheral T-cell Lymphomas
Date/Time: Sunday, December 8, 2019, 12:30 PM
Location: Orange County Convention Center, Orlando, FL, Valencia D (W415D)
The presentation from the 2019 ASH (Free ASH Whitepaper) Annual Meeting can be accessed by visiting the "News/Media" section of the Viracta website: View Source

Viracta has received Fast Track designation from the FDA for its proprietary investigational drug, nanatinostat, in combination with valganciclovir, in relapsed/refractory lymphomas, as well as Orphan Drug Designation for the treatment of post-transplant lymphoproliferative disorder, plasmablastic lymphoma, and angioimmunoblastic T-cell lymphoma.

About Nanatinostat
Nanatinostat (VRx-3996) is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class 1 HDACs which is key to inducing latent viral genes in EBV-associated malignancies. The nanatinostat and valganciclovir combination is being investigated in EBV-associated lymphomas in an ongoing Phase 2 clinical trial [NCT03397706].

About EBV-Associated Cancers
Approximately 95% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Under certain circumstances, such cells may undergo malignant transformation and become lymphoma. In addition to lymphomas, EBV is associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

Portola Pharmaceuticals Presents New Interim Data from Ongoing Phase 2a Study of its Oral SYK/JAK Inhibitor Cerdulatinib in Heavily Pre-Treated T-Cell Malignancies

On December 8, 2019 Portola Pharmaceuticals, Inc. (Nasdaq: PTLA) reported new interim results from the Company’s ongoing Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK inhibitor, in patients with specific subtypes of T-cell Non-Hodgkin Lymphoma, including relapsed/refractory peripheral T-cell lymphoma (PTCL); angioimmunoblastic T-cell lymphoma (AITL), a subset of PTCL; and cutaneous T-cell lymphoma (CTCL) (Press release, Portola Pharmaceuticals, DEC 8, 2019, View Source [SID1234552064]). The data will be presented today during an oral session at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando (December 7-10).

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As of the November 12, 2019 cut-off date, 64 PTCL patients and 40 CTCL patients treated with cerdulatinib as a single agent were evaluable for response. The overall response rate (ORR) was 34% in the PTCL cohort and 43% in the CTCL cohort. Among the subset of patients in the PTCL cohort with AITL, the ORR was 52% and the complete response rate (CR) was 37%.

"Relapsed or refractory PTCL and CTCL remain challenging diseases to treat given their heterogenous nature and lack of uniformly effective therapies," said Steven M. Horwitz, M.D., an oncologist at Memorial Sloan Kettering Cancer Center. "I am encouraged to see these updated results, which underscore the potential of cerdulatinib to address a range of rare, aggressive sub-types of T-cell malignancies as well as benefits in terms of quality-of-life measures, such as pruritus, which can be a significant burden for patients with cutaneous lymphomas."

Among the 64 patients in the PTCL cohort, 14 patients (22%) achieved a CR and eight patients (12%) achieved a partial response (PR). In the subgroup of 27 patients with AITL, 10 patients (37%) achieved a CR, and four patients (15%) achieved a PR. The median duration of response is eight months for all PTCL patients and is greater than nine months in AITL patients. Follow-up is ongoing.

Among the 40 patients in the CTCL cohort, three patients (8%) achieved a CR and 14 patients (35%) achieved a PR. Importantly, rapid improvements in pruritus, or severe itching – a common and often serious condition associated with CTCL – have been observed, as measured by the Likert scale.

Cerdulatinib demonstrated good tolerability in both PTCL and CTCL. The most common Grade 3 or greater adverse events across the PTCL and CTCL cohorts with a frequency > 5% were lipase increase (25%), amylase increase (19%), neutropenia (12%), anemia (10%), diarrhea (8%), sepsis/bacteremia (6%), and febrile neutropenia (4%). The lipase and amylase changes were generally asymptomatic and not associated with pancreatitis.

"We are encouraged by the continued safety and efficacy profile of cerdulatinib in patients with PTCL and CTCL, and the potential it has to meet medical needs through dual SYK and JAK pathway inhibition as the most advanced therapy of its kind currently in development for oncology," said Jeff Myers, Portola’s interim chief medical officer. "We look forward to the planned initiation of our registrational trial in patients with PTCL in the coming months, and to gathering additional evidence on the clinical activity of cerdulatinib."

ASH Oral Session Details – Sunday, December 8, 2019, at 12:45 p.m. EST

Title:

A Phase 2 Study of the Dual SYK/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability and Clinical Response in Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma

Session:

624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Novel Therapies in Peripheral T-cell Lymphomas

Presenter:

Steven M. Horwitz, M.D., Memorial Sloan Kettering Cancer Center

Location:

Valencia D (W415D), Level 4 (Orange County Convention Center)

About the Phase 2a Study
The Phase 2a, open-label study was designed to assess the safety and efficacy of cerdulatinib in patients with specific subtypes of relapsed/refractory T-cell Non-Hodgkin Lymphoma – including PTCL and CTCL, B-cell Non-Hodgkin lymphoma alone or in combination with rituximab, chronic lymphocytic leukemia, and small lymphocytic lymphoma.

About Cerdulatinib

Cerdulatinib is an investigational oral, dual spleen tyrosine kinase (SYK) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways implicated in certain hematologic malignancies and autoimmune diseases. There is a strong rationale for inhibiting both SYK (B-cell receptor pathway) and JAK (cytokine receptors) in B-cell malignancies where both targets have been shown to promote cancer cell growth and survival.

The U.S. Food and Drug Administration granted cerdulatinib Orphan Drug Designation for the treatment of PTCL in September 2018.

Bristol-Myers Squibb Announces Studies Evaluating liso-cel in Multiple Additional Patient Populations, Site of Care and Disease Areas Presented at American Society of Hematology (ASH) Annual Meeting

On December 8, 2019 -Bristol-Myers Squibb Company (NYSE: BMY) reported data from multiple studies evaluating lisocabtagene maraleucel (liso-cel), an investigational CD19-directed CAR T-cell therapy with a defined composition of purified CD8+ and CD4+ CAR T cells, were presented during the 2019 ASH (Free ASH Whitepaper) Annual Meeting in Orlando, Fla (Press release, Bristol-Myers Squibb, DEC 8, 2019, View Source [SID1234552063]). These studies included an evaluation of liso-cel in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) (TRANSCEND CLL 004); a study in second-line patients with relapsed or refractory large B-cell non-Hodgkin’s lymphoma (NHL) patients who were ineligible for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) (PILOT); and a separate analysis of patients with relapsed/refractory large B-cell non-Hodgkin lymphoma who received liso-cel in the outpatient setting across three studies.

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"As we continue to evaluate liso-cel in important new disease settings and areas of unmet medical need, we are encouraged to see the early results from these studies," said Stanley Frankel, M.D., Senior Vice President, Cellular Therapy Development for Bristol-Myers Squibb. "The results in relapsed or refractory CLL and SLL demonstrated a high rate of durable complete responses achieved in heavily pre-treated patients, including patients who have failed ibrutinib and venetoclax. We are encouraged by the potential of liso-cel to treat second-line relapsed or refractory large B-cell NHL patients who are not able to undergo a stem cell transplant. Finally, the analysis evaluating liso-cel administered in the outpatient setting demonstrates that not all patients require hospitalization and that the safety and efficacy profile across a variety of types of clinical sites is consistent."

TRANSCEND CLL 004

In the phase 1/2 TRANSCEND CLL 004 study, at the data cutoff, 23 patients with CLL/SLL who had received at least three (standard-risk disease) or two (high-risk disease) prior treatments were evaluable for safety, with 22 patients evaluable for efficacy. Patients had a median of 5 prior lines of therapy (range 2-11). All patients (23/23) had received prior ibrutinib and most (21/23) were refractory to or had relapsed on the BTK inhibitor. There were nine patients (39%) that had failed both a BTK inhibitor (progressed on treatment) and venetoclax (did not achieve a response after at least 3 months). Most patients (83%) had high-risk features including deletion 17p (35%, 8/23) and TP53 mutation (61%, 14/23). Patients received liso-cel target doses of either 50 × 106 (n=9) or 100 × 106 (n=14) CAR+ T cells following lymphodepletion.

Treatment-emergent adverse events (TEAE) of any grade occurred in 100% (23/23) of patients with 96% (22/23) of patients experiencing a grade 3 or higher TEAE. The most common grade 3 or higher TEAEs occurring in at least 25% of patients were anemia (78%, 18/23), thrombocytopenia (70%, 16/23), neutropenia (56.5%, 13/23), leukopenia (43.5%, 10/23), febrile neutropenia (26%, 6/23), lymphopenia (26%, 6/23) and cytokine release syndrome (9%, 2/23).

Seventy-four percent (17/23) of patients had cytokine release syndrome (CRS) of any grade with 9% of patients (2/23) experiencing grade 3 CRS. Thirty-nine percent (9/23) of patients had neurological events (NE) of any grade, while 22% (5/23) of patients had grade 3 or higher NE. Median time to onset of CRS was 4 days (range 1-10 days) and of NE was 4 days (range 2-21). Incidence and severity of CRS and NEs were similar for patients who failed a BTK inhibitor and venetoclax. Seventy-four percent (17/23) of patients received tocilizumab and/or corticosteroids. There were no grade 5 events.

At a median follow-up of 11 months, the overall response rate (ORR) for patients receiving liso-cel was 81.5% (18/22, 95% CI: 59.7 – 94.8) with 45.5% (10/22) of patients achieving a complete response (CR). In patients that had failed a BTK inhibitor and venetoclax, the ORR was 89% (8/9, 95% CI: 51.8 – 99.7) with 67% (6/9) achieving a CR. By day 30 following treatment, 68% (15/22) of patients had achieved an early objective response with 10 of 12 responders at 6 months remaining progression-free after at least 9 months, and eight patients in response at 12 months or longer. Among 20 patients evaluable for minimal residual disease (MRD), the majority achieved undetectable MRD in the blood (75%) and bone marrow (65%) by next-generation sequencing. All patients who achieved undetectable MRD have maintained this status at last follow-up.

PILOT

In the phase 2 PILOT study, patients had relapsed/refractory large B-cell NHL, had received only 1 prior line of immunochemotherapy and had been deemed ineligible for HSCT due to patient factors including age, comorbidities or performance status. Patients received liso-cel at a target dose of 100 × 106 CAR+ T cells following lymphodepletion and could be treated in the outpatient setting at the investigator’s discretion.

At the time of data cutoff, 19 patients had been leukapheresed, with 13 patients receiving lymphodepletion followed by liso-cel.

Of the 13 patients, eight (61.5%) had at least one grade 3 or higher TEAE and these were primarily cytopenias. Four patients (31%) had prolonged grade 3 or higher cytopenias at day 29. No patients had grade 3 or higher CRS and no patients experienced NE of any grade. Grade 1-2 CRS occurred in 3 (23%) patients. There were no grade 5 TEAEs. Finally, of the 6 patients treated in the outpatient setting, none were admitted to the hospital in the first 29 days following liso-cel infusion.

All 12 (100%) patients eligible for response evaluation achieved a response with 6 (50%) patients achieving a CR. Seven of 12 (58%) patients maintained response levels at 3 months following liso-cel infusion.

Outpatient Administration

A report of the safety and efficacy of liso-cel in patients with relapsed/refractory large B-cell NHL treated in the outpatient treatment setting was also presented. The analysis encompassed three studies including OUTREACH (n=13), the only trial evaluating CAR T-cell therapy in an outpatient setting at non-university centers, including treatment sites not accredited by the Foundation for the Accreditation of Cellular Therapy. The analysis also included TRANSCEND NHL 001 (n=25) and PILOT (n=6).

Outpatient treatment required patient education regarding CAR T-cell therapy, a caregiver and proximity to the treatment location. Additionally, each site was required to have specific readiness plans for patient care and monitoring for AEs, such as CRS and NE, in the outpatient setting.

In the analysis, at data cutoff, 44 patients treated in the outpatient setting from across the studies were evaluated and received liso-cel on day 1. Seventeen (39%) patients had CRS of any grade, while 13 (30%) patients had NE (n=13) of any grade. There was 1 case of grade 3 or higher CRS and 2 cases of grade 3 or higher NE and these were reversible. A total of 9 patients received supportive tocilizumab and/or corticosteroids. Fifty-five percent (24/44) of patients required hospitalization at some point and these were all from TRANSCEND or OUTREACH. Of these patients, 9 (20%) were admitted on study day 4 or earlier. Two (5%) patients required intensive care unit-level care lasting a median of 4 days. No patients from PILOT were admitted to hospital in the first 29 days. Following treatment, the median time to hospitalization was 5 days (range 2-22) and the median length of stay was 6.5 days (range 1-23). TEAEs of any grade reported in at least 20% of patients included fatigue, neutropenia, decreased appetite, CRS, anemia, constipation, nausea, headache, cough, dizziness, hypotension, thrombocytopenia, vomiting, back pain, diarrhea hypomagnesemia and tremor.

Across the studies, the ORR was 80% (35/44) with 55% (24/44) of patients achieving a complete response.

Liso-cel is not approved for any indication in any country.

Bristol-Myers Squibb: Advancing Cancer Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Lisocabtagene Maraleucel (liso-cel)

Liso-cel is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. Liso-cel CAR T cells aim to target CD19 expressing cells through a CAR construct that includes an anti-CD19 single-chain variable fragment (scFv) targeting domain for antigen specificity, a transmembrane domain, a 4-1BB costimulatory domain hypothesized to increase T-cell proliferation and persistence, and a CD3-zeta T-cell activation domain. The defined composition of CD4+ and CD8+ CAR T cells in liso-cel may limit product variability; however, the clinical significance of defined composition is unknown.

Updated Clinical Data from Phase 2 SPiReL Study Evaluating DPX-Survivac as a Combination Therapy in r/r DLBCL Presented at 61st American Society of Hematology (ASH) Annual Meeting

On December 8, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of immunotherapies, reported that updated results from SPiReL, an ongoing Phase 2 investigator-sponsored study of DPX-Survivac in combination with pembrolizumab in patients with recurrent/refractory diffuse large B-cell lymphoma (r/r DLBCL), were presented in a poster session at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, FL (Press release, IMV, DEC 8, 2019, View Source [SID1234552062]). The poster, which included additional data collected between the abstract submission and the presentation, continued to demonstrate a favorable therapeutic profile and treatment-associated clinical benefit in r/r DLBCL patients who received the DPX-Survivac combination regimen.

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"These updated data show encouraging clinical activity in patients treated with a DPX-Survivac combination regimen for recurrent/refractory diffuse large B-cell lymphoma," said Neil Berinstein, MD, FFCPC, ABIM, hematologist at Sunnybrook Health Sciences Centre and lead investigator for the clinical trial. "In contrast, both to standard-of-care treatments and other immunotherapeutic approaches in development, to observe this clinical benefit alongside a favorable safety profile highlights DPX-Survivac’s potential to reach this patient population in dire need of better treatment options."

"These results demonstrate a robust response in evaluable patients who received the combination regimen including DPX-Survivac, which continues to exhibit a promising therapeutic profile for patients with hard-to-treat cancers," said Joanne Schindler, M.D., D.V.M., Chief Medical Officer of IMV. "These data further validate DPX-Survivac’s novel mechanism, extending previously documented results in solid cancers now to survivin-expressing hematologic malignancies, and support the hypothesis that our lead candidate works well in combination with checkpoint inhibitors. We believe this represents a potentially meaningful alternative to more toxic chemotherapy regimens; and, with this foundation, we look forward to topline results from this study as we prepare to launch an IMV-sponsored study in r/r DLBCL in 2020."

Updated Clinical Data from the SPiReL Study

In the poster presentation at ASH (Free ASH Whitepaper), Dr. Berinstein reported updated clinical results from the ongoing Phase 2 SPiReL study. Highlights of this preliminary data are outlined below:

7/9 (77.8%) evaluable subjects exhibited clinical benefit, including three (33.3%) complete responses and two (22.2%) partial responses;
Reproducible survivin-specific T cell responses observed in all subjects that achieved clinical responses on treatment;
One subject, who received three prior lines of systemic therapies and failed autologous stem cell transplant, reached a complete response at the first on-study scan following treatment with the DPX-Survivac combination regimen and remains free of disease recurrence after completing the study; and
Clinical benefits and favorable toxicity profile observed in a heterogenous population of r/r DLBCL patients, including patients of advanced age and/or with comorbidities, who are more susceptible to adverse effects and more difficult to treat.
As of December 1, 2019, 17 subjects have been enrolled in the study.

Conference Call Information:

IMV will host a conference call and webcast on Monday, December 9, 2019 at 8:00 a.m. EST to discuss the DPX-Survivac clinical results presented at ASH (Free ASH Whitepaper).

Financial analysts are invited to join the conference call by dialing (866) 211-3204 (U.S. and Canada) or (647) 689-6600 (International) using the conference ID number: 8796370. Other interested parties will be able to access the live audio webcast at this link: http://bit.ly/IMV_ASH19.

The webcast will be recorded and available on the IMV website for 30 days following the call. The poster and the webcast will available on the Investors section of the company’s website, under "Events, Webcasts & Presentations".

About the SPiReL Study

"SPiReL" is a Phase 2 non-randomized, open label, efficacy and safety study. Eligible subjects have persistent or recurrent/refractory DLBCL, confirmed expression of survivin and are not eligible for curative therapy. Study treatment includes administering two doses of 0.5 mL of DPX-Survivac 3 weeks apart followed by up to six 0.1 mL doses every 8 weeks. Intermittent low dose cyclophosphamide is administered orally at 50 mg twice daily for 7 days followed by 7 days off. Pembrolizumab 200 mg is administered every 3 weeks. Study participants continue active therapy for up to one year or until disease progression, whichever occurs first.

The primary objective of this study is to document the response rate to this treatment combination using modified Cheson criteria. Secondary objectives include duration of response and safety. Exploratory endpoints include T cell response, tumor immune cell infiltration, and gene expression analysis.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable CD8+ T cell generation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to chemotherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication.