On December 6, 2020 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune disease, reported updated data from its ongoing Phase 1 dose-escalation study of vibecotamab (XmAb14045), a CD123 x CD3 bispecific antibody, in patients with relapsed or refractory acute myeloid leukemia (AML) (Press release, Xencor, DEC 6, 2020, View Source [SID1234572255]). The data were presented in an oral session at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Farhad Ravandi, M.D., Professor of Medicine and Chief of the Section of Acute Myeloid Leukemia in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center.

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"Vibecotamab has meaningful clinical activity in relapsed AML, and responses appear to be associated with lower baseline disease burden, indicated by patients with lower blast percentages and lower PD1 expression on CD8+ and CD4+ T cells. This suggests possible strategies to select patients most likely to respond," said Dr. Ravandi. "Responses including CRs and CRis have been durable, lasting many months, in several patients."

"Additionally, we continue to observe that vibecotamab’s primary toxicity, CRS, is generally mild-to-moderate in severity when observed, and our mitigation strategy, which includes a combination of dose-modifying measures, has been effective in limiting its severity," said Allen Yang, M.D., Ph.D., senior vice president and chief medical officer. "With a manageable profile and encouraging potential in certain patient populations, such as myelodysplastic syndromes and AML with minimal residual disease, we are now planning our next steps to develop vibecotamab for these patients, along with our partner Novartis."

Key Highlights from the Presentation

At data cut off on October 28, 2020, 112 patients with relapsed or refractory AML had received vibecotamab. Patients were a median of 64 years old and were heavily pretreated, having had a median of three prior therapies and 30% (n=34) with a history of allogeneic hematopoietic stem cell transplantation. 86% of patients (n=96) were refractory to their last therapy, and 62% (n=69) were categorized as adverse risk at diagnosis by the European LeukemiaNet (ELN 2017) system. The study is ongoing, and additional patients are being enrolled.

Cytokine release syndrome (CRS) was the most common toxicity occurring in 61% of patients (n=68), and 9% of patients (n=10) experienced CRS at Grade 3 or higher. The majority of CRS was observed in the first dose and was generally manageable with premedication. Additional mitigation measures included selecting a lower priming dose, avoiding weekly dose step-up, and more frequent dosing in the first week to allow a higher cumulative exposure and to avoid the potential CD123 antigen sink. There was no evidence of drug related myelosuppression. Neurological events were infrequent and primarily Grade 1 and Grade 2 headaches.

The efficacy analysis included 54 evaluable patients who received a dose of at least 0.75 mcg/kg, completed at least the first cycle of treatment and had at least one post-treatment disease assessment. Two patients achieved complete remission (CR), and three patients achieved a CR with incomplete hematologic recovery. Additionally, two patients reached a morphologic leukemia-free state, and one patient experienced partial remission, as assessed by the investigator. The overall response rate (ORR) was 15% (n=8/54).

Biomarker analyses suggest that low baseline leukemic burden and low PD-1 expression on CD4+ and CD8+ T cells are independent predictors of response. Seven responders had a baseline blast count less than or equal to 25% blasts in bone marrow. The ORR increased to 26% (n=7/27) when using this threshold to define the population with low disease burden for the analyses.

The presentation will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

About Vibecotamab

Vibecotamab (XmAb14045) is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on vibecotamab. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by vibecotamab activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

On December 6, 2020 Kite, a Gilead Company (Nasdaq: GILD), reported results from the interim analysis of ZUMA-12, a multicenter, open-label, single-arm Phase 2 study evaluating Yescarta (axicabtagene ciloleucel) as first-line therapy in patients with high-risk large B-cell lymphoma (LBCL) (Press release, Kite Pharma, DEC 6, 2020, View Source [SID1234572254]). After a single infusion of Yescarta, 85 percent of patients achieved a response (n=27 evaluable for efficacy), including 74 percent of patients with a complete response. The data were presented in an oral session during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #405).

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"Despite well-established standard treatment regimens in newly diagnosed large B-cell lymphoma, patients with high-risk disease are underserved by currently available treatment options," said Sattva S. Neelapu, MD, Professor, Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "Only half of these patients achieve long-term remission with standard first-line therapy, so there is a major need for therapies with potential to improve outcomes for more patients. These early results from the ZUMA-12 trial are highly encouraging for the potential of CAR T in this earlier setting in patients with high risk."

Among evaluable patients with centrally confirmed high-risk LBCL with at least one month of follow-up (n=27), 85 percent of patients responded, including 74 percent with a complete response. With a median follow-up of 9.3 months, 70 percent of response-evaluable patients were in an ongoing response at data cut-off, per investigator assessment. Median progression-free survival, median overall survival and median duration of response were not reached after a median follow-up of 9.5 months.

Among all safety-evaluable patients who received any dose of Yescarta with at least one month of follow-up (n=32), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events (NE) occurred in 9 percent and 25 percent of patients, respectively. No Grade 5 CRS or NEs occurred. There was one Grade 5 adverse event due to COVID-19.

"Yescarta has already presented four-year survival data in patients with third-line refractory LBCL and we are now excited for what these ZUMA-12 results signal for its potential in earlier lines of treatment," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "As the first positive results for a CAR T as a first-line therapy, these data are a tremendous step forward as we work to bring the benefits of Yescarta to more patients with this disease."

Kite has presented four-year survival data for Yescarta in the ZUMA-1 study of patients with refractory large B-cell lymphoma. Based on these data and other data presented at ASH (Free ASH Whitepaper), Kite believes that Yescarta could bring the hope of survival to patients with a number of other hematological malignancies.

Yescarta was the first chimeric antigen receptor (CAR) T cell therapy to be approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), and high grade B-cell lymphoma and DLBCL arising from FL. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a risk evaluation and mitigation strategy (REMS) due to these risks; see below for Important Safety Information.

About ZUMA-12

ZUMA-12 is a multicenter, open-label, single-arm Phase 2 study that aims to enroll approximately 40 adult patients (≥18 years old) with high-risk LBCL. Patients who met the following criteria for high-risk LBCL were considered eligible for the study: double- or triple-hit lymphoma by fluorescent in situ hybridization per investigator or LBCL with IPI score ≥3; and positive interim PET per Lugano Classification after two cycles of an anti-CD20 monoclonal antibody- and anthracycline-containing regimen. Patients underwent leukapheresis (≥ two weeks after prior systemic therapy) and optional non-chemotherapy bridging at investigator discretion, followed by conditioning chemotherapy.

The primary endpoint of the trial is complete response rate per the Lugano Classification. Key secondary objectives include objective response rate, duration of response, event-free survival (EFS), progression-free survival, overall survival, frequency of adverse events, and levels of CAR T cells and cytokines in blood and serum. The study is ongoing.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of patients, with 13% ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to Yescarta infusion. Following infusion, monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES occurred in 87% of patients, 98% of which occurred within the first 8 weeks with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade ≥3 occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%), and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures, as well as fatal and serious cases of cerebral edema have occurred. Following Yescarta infusion, monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients. Grade ≥3 infections occurred in 23% of patients; those due to an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade ≥3 cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common (incidence ≥20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

On December 6, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported results from pooled analyses of long-term follow-up from multiple clinical trials evaluating the use of IMBRUVICA (ibrutinib) monotherapy and in combination as first-line treatment for patients with chronic lymphocytic leukaemia (CLL) with high-risk features (Press release, Janssen Pharmaceuticals, DEC 6, 2020, View Source [SID1234572253]). The data were presented at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Results from an integrated analysis of two clinical trials with up to 79 months of follow-up (Abstract #2220)1 demonstrated similar progression-free survival (PFS) and overall response rates (ORR) with ibrutinib in patients with or without high-risk genomic features, and further showed significant PFS and ORR benefits with ibrutinib compared with chlorambucil-based therapy regardless of genomic risk features.1

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In addition, data with a median follow-up of more than four years were presented from a pooled analysis of 89 patients with high-risk CLL bearing TP53 aberrations from four clinical trials showing that first-line treatment with ibrutinib resulted in sustained efficacy, including PFS, suggesting that ibrutinib has meaningfully improved the poor prognosis in this high-risk population (Abstract #2219).2

"These large integrated data sets with follow-up up to six years, in addition to other data presented at the meeting in similar populations, contribute to the accumulating evidence supporting the clinically meaningful, long-term treatment benefit of ibrutinib as first-line therapy for patients with CLL," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "Ibrutinib is an approved standard of care in first-line treatment of CLL, and the data presented at the ASH (Free ASH Whitepaper) Annual Meeting further demonstrate the durability of responses in CLL patients with traditional high-risk features."

Two additional studies will be presented in the oral sessions showing real-world treatment patterns or outcomes in patients with CLL treated outside of a clinical trial setting. The first study is a U.S. retrospective analysis describing treatment patterns and time to next treatment (TTNT) in patients with high-risk CLL treated with first-line ibrutinib or chemoimmunotherapy (CIT) (Abstract #372).3 In this U.S. retrospective study, the largest of its kind to date, patients with high-risk CLL treated with single-agent ibrutinib had significantly longer TTNT compared with patients treated with first-line CIT.3 In the second oral presentation, results from the U.S. informCLL registry (Abstract #547) highlighted infrequent prognostic biomarker testing rates prior to initiating CLL therapy, and limited use of such information to guide optimal treatment selection for many patients with high-risk CLL, suggesting an opportunity for additional education of healthcare providers.4

Integrated Analysis of the Phase 3 RESONATE-2 and iLLUMINATE Trials Evaluated Outcomes of First-Line Ibrutinib in Patients with CLL and High-Risk Genomic Features with up to 6.5 Years Follow-up (Abstract #2220)1
Data were presented from a pooled analysis of two Phase 3 studies (RESONATE-2 and iLLUMINATE) with up to 79 months of follow-up evaluating ibrutinib-based therapy in first-line treatment of CLL patients with various high-risk genomic features.1

Key Study Findings:

In patients treated with ibrutinib-based therapy, PFS was comparable between patients with, versus without, specified high-risk genomic features, including del(17p)/TP53 mutated/BIRC3 mutated, the highest risk category.1
At 42 months, PFS rates were significantly higher across all high-risk genomic subgroups in previously untreated patients treated with ibrutinib-based treatment (63 to 82 percent) compared with those receiving chlorambucil-based treatment (6 to 34 percent) with or without obinutuzumab, regardless of mutation.1
At a median duration of ibrutinib treatment of 35.7-43.8 months across high-risk subgroups, there were no meaningful differences in the rates of treatment-emergent adverse events (AEs) of any Grade, or Grade 3 or greater AEs compared to those of the overall population.1
"Certain genomic abnormalities and mutations are predictors of inferior outcomes with chemoimmunotherapy in patients with CLL," said Jan A. Burger,* M.D., Ph.D., Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and principal study investigator. "Chemoimmunotherapy remains common in real-world practice despite evidence that shows small molecule inhibitor therapies like ibrutinib have demonstrated improved outcomes in high-risk patients compared to chemoimmunotherapy."

"Since its first European approval in 2014, ibrutinib has redefined treatment paradigms for CLL, and these study results offer further evidence of the benefits and tolerability ibrutinib offers to CLL patients," adds Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "For high-risk CLL patients, the treatment landscape has advanced dramatically, with ibrutinib continuing to play a major role in defining what it means to live with genetic variations of this disease, which have historically poor outcomes."

Large, Pooled, Multi-Study Dataset Assessed Long-Term Benefit of First-Line Ibrutinib-Based Treatment in Patients with TP53 Aberrations with up to Four Years Follow-up (Abstract #2219)2
Data were presented from a pooled analysis of four clinical studies evaluating the long-term efficacy and safety of first-line ibrutinib-based therapy in CLL patients with TP53 aberrations present.2 The four studies were: RESONATE2; iLLUMINATE; the E1912 study designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH); and the 1122e study sponsored by the National Heart, Lung, and Blood Institute (NHLBI).2

Key Study Findings:

With a median follow-up of 50 months, median PFS was not reached (95% CI: 67 months to not estimable).2 At 48 months, the PFS rate was 79 percent and the OS rate was 88 percent among high-risk patients treated with ibrutinib monotherapy.2
Additionally, 46 percent of patients with TP53 aberrations remained on ibrutinib treatment and 39 percent had a complete response.2
No new safety signals were identified in this analysis and in general the rates of Grade ≥3 AEs of clinical interest declined after the first year of ibrutinib treatment.2
Clinical Outcomes Among Real-World Patients with CLL Initiating First-Line Ibrutinib or Chemoimmunotherapy Stratified by Risk Status: Results From a U.S. Retrospective Chart Review Study (Abstract #372)3
Data were presented as an oral presentation from a large real-world study comparing clinical outcomes (TTNT) in high-risk and non-high-risk patients with CLL receiving ibrutinib compared to CIT in the first-line setting.3

Key Study Findings:

Data presented showed that high-risk patients receiving ibrutinib significantly prolonged TTNT compared to those receiving CIT.3
Ibrutinib also provided sustained clinical benefit regardless of risk status, which is consistent with clinical trial results.5,6,7
This study highlighted the need for cytogenetic/molecular testing before CIT treatment, consistent with clinical treatment guidelines.8,9
Real-World Prognostic Biomarker Testing, Treatment Patterns, And Dosing Among Patients With CLL From the informCLL Prospective Observational Registry (Abstract #547)
An oral presentation on Monday, December 7, will feature results from the informCLL real-world prospective observational registry assessing treatment patterns in the era of novel agents.4

Key Study Findings:

The most common index treatment was ibrutinib; the majority of patients treated with ibrutinib remained on therapy at two-year follow-up; and CIT was also used for one-third of patients.4
Data also demonstrated that prognostic biomarker testing rates were poor, especially for the biomarkers TP53 and IGHV.4
Data from informCLL also indicate a ‘knowledge gap’ in terms of prognostic marker testing, interpretation and selection of optimal therapies for patients with high-risk disease.4
*Jan A. Burger is a principal study investigator and was not compensated for any media work

#ENDS#

About Ibrutinib
Ibrutinib is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.10 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signalling is needed by specific cancer cells to multiply and spread.11 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.12

Indications for which ibrutinib is approved in Europe include:10

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with rituximab or obinutuzumab 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 received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 100 countries for at least one indication, and to date, has been used to treat more than 200,000 patients worldwide.13

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.14 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.15 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.16

The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

On December 6, 2020 IMV Inc. (Nasdaq:IMV; TSX:IMV) ("IMV" or the "Company"), a clinical-stage biopharmaceutical company pioneering a novel class of cancer immunotherapies and vaccines against infectious diseases, today announces that durable clinical benefits induced by combination treatment of IMV’s T cell therapy with Merck’s Keytruda (pembrolizumab) in subjects with PD-L1 positive recurrent/refractory Diffuse Large B Cell Lymphoma (r/r DLBCL) have been presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, IMV, DEC 6, 2020, View Source [SID1234572252]).

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"Compared to currently approved therapies, this combination has demonstrated a promising duration of response with limited adverse events in this difficult-to-treat patient population," said Dr. Neil Berinstein, principal investigator of the SPiReL study and hematologist at Sunnybrook Health Sciences Center. "The improved clinical response in this subset of patients with PD-L1 expression is an exciting scientific finding. The baseline PD-L1 expression is a potential predictor of response to this treatment combination which may not be attributed to the activity of pembrolizumab alone1 and is more likely caused by the complementary mechanisms of action of these two immunotherapies."

"These are exciting early data and the potential synergistic action of these two immunotherapies paves the way for a new treatment paradigm with combination therapeutics," said Dr. Joanne Schindler, Chief Medical Officer at IMV. "We are also evaluating this combination therapy with Merck in other solid tumor indications and we look forward to exploring further the potential of what we have seen in the SPiReL study."

In his presentation during the annual ASH (Free ASH Whitepaper) meeting, Dr. Neil Berinstein describes the results from the SPiReL study:

In the PD-L1+ population (n=7), subjects
Have significantly higher median Progression Free Survival (PFS) of 230 days, compared to the PD-L1 negative subjects (70 days) with a p-value of 0.007, suggestive of a strong predictive biomarker for this treatment combination,
Demonstrated an objective response in six subjects, including three subjects who have completed one-year of study treatment,
Demonstrated an ORR and a DCR at both 85.7%.
Peripheral blood was assessed for survivin-specific ELISpot responses in 15 subjects with available samples. All 3 subjects with a CR, and 3 of 4 subjects with a PR had positive ELISpot responses while only 1 subject with SD and 1 subject with PD demonstrated survivin-specific ELISpot response, suggestive of an association between the clinical responses with the mechanism of action of DPX-Survivac.
Treatment was well tolerated. The majority of treatment-related adverse events were grade 1 and 2 severity. A majority of these were injection site reactions associated with the subcutaneous administration of DPX-Survivac.
The poster presentation by Dr. Berinstein is available under the Scientific Publications & Posters section on IMV’s website and is also available on the ASH (Free ASH Whitepaper) meeting platform.

Biomarkers associated with clinical response were also discussed in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting, and during a webcast hosted by IMV on November 12, 2020.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapy that generates targeted and sustained cancer cell killing capabilities in vivo. Treatments with the DPX-Survivac T cell therapy have demonstrated a favorable safety profile across all clinical studies.

IMV’s T cell therapy, DPX-Survivac, consists of survivin-based peptides formulated in IMV’s proprietary delivery platform (DPX). IMV’s lead compound is designed to generate a sustained cytotoxic T cell 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.

About the SPiReL Study

"SPiReL" is a Phase 2 non-randomized, open label, efficacy, and safety study of a novel immunotherapy combination with DPX-Survivac and pembrolizumab. Intermittent low dose cyclophosphamide is given as an immune modulator. Subjects with r/r incurable DLBCL and survivin expression are eligible for participation. The primary outcome is to document the objective response rate using modified Cheson criteria for the combination treatment. Secondary objectives include safety, duration of response and time to next treatment. Exploratory endpoints include T cell response, tumor immune cell infiltration, and biomarker analysis. To date, 24 subjects have been enrolled.

On December 6, 2020 Gilead Sciences, Inc. (Nasdaq: GILD) reported updated results from the magrolimab Phase 1b trial. Magrolimab is an investigational, potential first-in-class, anti-CD47 monoclonal antibody being studied in previously untreated acute myeloid leukemia (AML) patients who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML (Press release, Gilead Sciences, DEC 6, 2020, View Source [SID1234572238]). The study continues to demonstrate high response rates with magrolimab in combination with azacitidine, with an overall response rate of 63% (n=27/43) among the total patient population and 69% (n=20/29) in TP53-mutant patients. The data were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #330).

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"In this ongoing study, treatment with magrolimab and azacitidine continues to achieve promising, durable responses in patients with AML who are ineligible for first-line chemotherapy," said David Sallman, MD, H. Lee Moffitt Cancer Center and Research Institute, an investigator for the clinical trial. "These findings are especially encouraging for patients with TP53 mutations, which are associated with poor outcomes and limited response to existing treatment options."

In the study, 64 patients were treated with magrolimab plus azacitidine, including 47 patients with the TP53 mutation, a treatment-refractory and poor-prognosis population. As of November 2020, 63% (n=27/43) of patients evaluable for efficacy achieved an objective response per European LeukemiaNet 2017 criteria, 42% (n=18/43) achieved a complete remission (CR), and 12% (n=5/43) achieved a CR with an incomplete count recovery (CRi). The median duration of response (DOR) was 9.6 months (range: 0.03+ to 18.7 months) and the median time to response was 1.95 months (range: 0.95 to 5.6 months).

For patients with the TP53 mutation, 69% (n=20/29) achieved a response, 45% (n=13/29) achieved a CR and 14% (n=4/29) achieved a CRi. The median DOR was 7.6 months (range: 0.03+ to 15.1+ months) and the minimum residual disease (MRD) negativity in patients with a CR/CRi was 29% (n=5/17).

Preliminary median overall survival (OS) for TP53-wild-type patients (n=16) was 18.9 months (95% CI: 4.34, NE) and for TP53-mutant patients (n=47) was 12.9 months (95% CI: 8.21, 17.28). The median follow-up for TP53-wild-type and TP53-mutant patients was 12.5 months and 4.7 months, respectively. Additional patients and longer follow-up in a comparative trial are needed to further characterize the survival benefit.

Treatment-related adverse events observed with over 15% incidence included anemia, fatigue, blood bilirubin increased, infusion related reaction, neutropenia, thrombocytopenia and ALT increase. Most patients were cytopenic at baseline, and no significant increased cytopenias, infections or immune-related adverse events (AEs) were observed in the study. Thirty-day all-cause mortality was 4.7% (n=3/64), and 60-day mortality was 7.8% (n=5/64). Treatment discontinuation due to drug-related AE occurred in 4.7% of all patients.

"We continue to be encouraged by the response rates seen in this study and are rapidly advancing the development of magrolimab based on its potential to help address significant unmet medical needs," said Daejin Abidoye, Senior Vice President, Head of Oncology, Gilead Sciences.

Magrolimab is investigational and not approved anywhere globally. Its efficacy and safety have not been established.

About Acute Myeloid Leukemia (AML)

AML is a type of cancer that starts in the bone marrow and can quickly move to the blood and other parts of the body. including the lymph nodes, spleen and central nervous system. AML most often develops from cells that would turn into red blood cells, neutrophils, and platelets but can also evolve from other blood disorders such as myelodysplastic syndromes. Approximately 20,000 Americans will be diagnosed with AML each year.

About the Study

The Phase 1b trial, funded in part by the California Institute of Regenerative Medicine (CIRM), is designed to evaluate the safety, tolerability and efficacy of magrolimab combined with azacitidine in untreated patients with AML who are ineligible for induction chemotherapy. All patients in the trial received a magrolimab 1 mg/kg priming dose, coupled with intrapatient dose escalation, to mitigate on-target anemia. Patients were then treated with full doses of azacitidine and a magrolimab maintenance dose of 30 mg/kg once weekly or every two weeks. Based on pharmacokinetics and CD47 receptor occupancy data in the bone marrow from the ongoing trial, dosing every two weeks has been selected to optimize patient convenience.

About Magrolimab

Magrolimab is a potential, first-in-class investigational monoclonal antibody against CD47 and a macrophage checkpoint inhibitor that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don’t eat me" signal used by cancer cells to avoid being ingested by macrophages. Magrolimab is being developed in several hematologic cancers, including myelodysplastic syndrome (MDS), as well as solid tumor malignancies.

The U.S. Food and Drug Administration (FDA) recently assigned Breakthrough Designation to magrolimab, in combination with azacitidine, for the treatment of adult patients with newly-diagnosed MDS including intermediate-, high-, or very high-risk tumor types. Magrolimab also received PRIME Designation for treatment of MDS from the European Medicines Agency (EMA). In addition, magrolimab received Fast Track Designation by the FDA for the treatment of MDS, AML, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma; and has been granted Orphan Drug Designation by the FDA and EMA for MDS and AML.