On December 3, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") reported updated results from a Phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in patients newly diagnosed with FLT3 mutation-positive (FLT3mut+) Acute Myeloid Leukemia (AML) (Press release, Astellas, DEC 3, 2018, View Source [SID1234531821]). The data were presented today in an oral presentation (Abstract 564) at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"A diagnosis of AML can be devastating for patients. It is a life-threatening disease and treatment usually needs to start as quickly as possible," said Keith W. Pratz, M.D., of John Hopkins Sidney Kimmel Comprehensive Cancer Center, who presented the data at the ASH (Free ASH Whitepaper) Annual Meeting. "Typical treatment for AML consists of induction and consolidation therapy. However, treatment options targeted for specific mutations may be important tools in physicians’ armamentarium of therapies for patients with AML. These results help advance our scientific understanding of how to potentially address these mutations in first-line treatment of AML."

The purpose of this ongoing, open-label dose escalation/expansion Phase 1 clinical study (NCT02236013) is to assess the safety, tolerability and antitumor effects of gilteritinib when combined with induction and consolidation chemotherapy, and as single-agent maintenance therapy, in adult patients with newly diagnosed AML.1

The two-part trial first enrolled patients to successive cohorts to determine the Maximum Tolerated Dose. Patients in the dose expansion cohort received gilteritinib at the recommended expansion dose established during dose escalation.

As of October 11, 2018, 68 subjects had been enrolled in the study; 66 are included in the safety analysis set. Of these patients, 36 (54.5%) had FLT3 mutations (FLT3-ITD, n=26). During dose-escalation, two patients in the 40 mg/day cohort who had received gilteritinib on days 1-14 experienced dose-limiting toxicities (DLTs; neutropenia, thrombocytopenia, decreased ejection fraction). After the gilteritinib induction schedule change, no more DLTs occurred at this dose. Two patients in the 200 mg/day cohort experienced DLTs (neutropenia, neutropenic enterocolitis). The maximum tolerated dose and the recommended expansion dose were established at 120 mg/day.

Additional key findings include:

The end-of-treatment investigator-reported rate of composite complete remission (CRc) for response evaluable FLT3mut+ subjects receiving gilteritinib 120 mg on Schedule 1 (n=17) was 100%.
The CRc rate in FLT3mut+ subjects receiving Schedule 2 induction with daunorubicin was also 100%.
The CRc rate in FLT3mut+ subjects receiving Schedule 2 induction with idarubicin was 66.7%.
Among subjects who received ≥80 mg/day gilteritinib (n=52), the CRc rate for FLT3mut+ subjects was 90.3% (n=28/31).
Median overall survival has not been reached. Median disease-free survival was 430 days (95% CI: 155, 630).
Grade ≥3 adverse events (AEs) in ≥10% of subjects were febrile neutropenia (63.6%), thrombocytopenia (19.7%), decreased platelet count (19.7%), decreased white blood cell count (19.7%), neutropenia (19.7%), decreased neutrophil count (16.7%), anemia (13.6%), and sepsis (10.6%).
Serious drug-related AEs in >1 subject were febrile neutropenia (n=11), sepsis (n=4), small intestinal obstruction, and decreased ejection fraction (both n=2).
Gilteritinib, under the brand name XOSPATA, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation as detected by an FDA-approved test.2 Gilteritinib is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations.

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a cancer that impacts the blood and bone marrow, and its incidence increases with age. The American Cancer Society estimates that in 2018, approximately 19,000 new patients will be diagnosed with AML in the U.S.3

About XOSPATA
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.2 XOSPATA is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations.

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize XOSPATA.

Important Safety Information

Contraindications
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

Warnings and Precautions
Posterior Reversible Encephalopathy Syndrome (PRES) There have been rare reports of PRES with symptoms including seizure and altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XOSPATA in patients who develop PRES.

Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patients treated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

Adverse Reactions
The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%).

Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (7%), cardiac failure (grouped terms) (4%), pericardial effusion (3%), pericarditis (2%), differentiation syndrome (1%), anaphylactic reaction (1%) and posterior reversible encephalopathy syndrome (1%).

Lab Abnormalities: The most common lab abnormalities (>20%) that were Grade ≥3 that occurred ≥10% were: hypophosphatemia (12%), alanine aminotransferase increased (12%), hyponatremia (12%), aspartate aminotransferase increased (10%).

Drug Interactions

Combined P-gp and Strong CYP3A Inducers: Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure, which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.

Strong CYP3A inhibitors: Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.

Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor: Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.

Specific Populations
Lactation: Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

On December 3, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported results from a prospective Phase 2 single-arm, open-label, multicenter clinical trial studying the management of oral mucositis with the use of oral leucovorin (d,l-folinic acid) as adjunct to FOLOTYN (pralatrexate) in patients with hematological malignancies, including PTCL and CTCL (Press release, Spectrum Pharmaceuticals, DEC 3, 2018, View Source [SID1234531838]). These new data were highlighted in a poster presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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Study results with a total of 35 patients demonstrated that use of leucovorin 25 mg tablets by oral administration for two days (a total of six doses [150 mg cumulative weekly dose]), initiated 24 hours after each FOLOTYN dose (30 mg/m2 IV administration, once weekly for six weeks in each cycle) reduced the rate of Grade 2 or greater mucositis significantly, to 5.7 percent (95% CI = 1 – 19%) from historic rate (52%) associated with FOLOTYN use. There were no reports of ≥ Grade 3 oral mucositis. Grade 1 oral mucositis was reported only in 4 (11%) patients. No patient omitted, delayed or reduced FOLOTYN dose due to oral mucositis with adjunct leucovorin therapy. The occurrence of mucositis, an impediment of FOLOTYN, has previously been reported at a rate of 52 percent at Grade 2 or higher in patients undergoing treatment with FOLOTYN in a registration study (PROPEL).1

"Mucositis is a frequent complication of FOLOTYN therapy, which can cause painful inflammation of the digestive tract. It is often managed by omitting, delaying, or reducing the dose of this medication in some patients," said Andrei R Shustov, MD, lead investigator, professor of medicine, hematology, University of Washington School of Medicine, and hematologist, Seattle Cancer Care Alliance. "We are excited about how significantly leucovorin was able to reduce the rate of mucositis in patients and believe this study established the foundation for the potential use of leucovorin as a preventive regimen for FOLOTYN patients."

"While previous studies have established the use of FOLOTYN as an option in relapsed or refractory PTCL patients, mucositis has been an issue that could impact treatment and quality of life," said Francois Lebel, MD, Chief Medical Officer, Spectrum Pharmaceuticals. "This is the first prospective study to suggest that leucovorin may prevent or reduce oral mucositis. These are welcome findings that merit further studies of leucovorin as an adjunct to FOLOTYN so we can one day provide definitive guidance to physicians to help reduce concerns of FOLOTYN treatment delay or discomfort due to oral mucositis."

About FOLOTYN

FOLOTYN, (pralatrexate injection), a folate analogue metabolic inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI International and Southern Research Institute and developed by Allos Therapeutics. In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from PROPEL, the pivotal study of FOLOTYN in patients with relapsed or refractory PTCL, was published in the March 20, 2011 issue of the Journal of Clinical Oncology.

Important FOLOTYN Safety Information

Warnings and Precautions

FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.

Mucositis may occur. If greater-than or equal to Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.

Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may occur. Monitor patients and treat if needed.

FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.

Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.

Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are greater-than or equal to Grade 3, omit or modify dose.

Adverse Reactions

The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.

Use in Specific Patient Population

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

Drug Interactions

Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.

On December 3, 2018 AstraZeneca and Acerta Pharma, its haematology research and development centre of excellence, have presented new, long-term follow-up results for Calquence (acalabrutinib) in patients with relapsed or refractory mantle cell lymphoma (MCL), and updated results of an ongoing clinical trial assessing Calquence monotherapy in treatment-naïve patients with chronic lymphocytic leukaemia (CLL), at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego, CA, USA (Press release, AstraZeneca, DEC 3, 2018, View Source [SID1234531822]).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "The data from these two clinical trials validate previous findings and add to the growing body of evidence that support the promise of Calquence in multiple blood cancers. We are very encouraged by these results, which reinforce our commitment to advancing innovative treatments for blood cancer patients."

Calquence follow-up data in MCL confirms efficacy and tolerability

Long-term follow-up data presented from the Phase II ACE-LY-004 trial in relapsed or refractory MCL showed sustained and clinically meaningful responses to Calquence with a median follow-up of more than two years (26 months), confirming its efficacy and safety profile in this patient population.1 Initial data from this trial served as the basis for the accelerated approval of Calquence by the US Food and Drug Administration in October 2017 and the first approval outside the US in November 2018 in the United Arab Emirates.3,4

Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL trial, said: "It’s encouraging to see the sustained duration of response in the updated analysis and the safety profile of acalabrutinib maintained consistently over time in MCL patients. As we gain more and more experience with this therapy, its importance as a treatment option for relapsed or refractory MCL is being more fully realised across the clinical and patient community."

Summary of key investigator-assesseda efficacy results from the open-label, single-arm clinical trial of Calquence in 124 adult patients with relapsed or refractory MCL1:

Efficacy measure Result (N=124; 95% CIb)
Overall response rate

(Complete response + partial response)

81% (73, 87)

Best response

Complete response

43% (34, 52)

Partial response

38% (29, 47)

Stable disease

9% (5, 15)

Progressive disease

8% (4, 14)

Not evaluablec

2% (1, 7)

Median duration of response

26 months (17.5, not reached)

Median progression-free survival

20 months (16.5, 27.7)

a Response was assessed based on the Lugano classification.

b Confidence interval (CI).

c Includes patients without any adequate post-baseline disease assessment.

The median follow-up was 26 months, with 40% of patients remaining on treatment with Calquence at the time of analysis. An exploratory analysis of the trial found that an undetectable minimal residual disease status was achieved in a sub-set of patients.

In this trial, the most frequent adverse events (AEs; ≥ 20%, all grades) were headache (38%), diarrhoea (36%), fatigue (28%), cough (22%) and myalgia (21%). These events were primarily Grade 1/2. Grade 3/4 AEs (≥ 5%) were anaemia (11%), neutropoenia (11%) and pneumonia (6%). There were 13 patients (10%) with 16 cardiac events including four Grade 3/4 events, each in one patient (acute coronary syndrome, acute myocardial infarction, cardiorespiratory arrest, coronary artery disease). There was no new onset of atrial fibrillation. Bleeding events occurred in 33% of patients, most frequently contusion (13%) and all bleeding events but three (2%, Grade 3) were Grade 1/2 events. Ten patients discontinued treatment due to AEs. In total there were six deaths due to AEs (none of which were considered to be related to Calquence).1

New data from ongoing CLL clinical trial demonstrate strong efficacy

Updated results of the Phase I/II ACE-CL-001 trial were presented today in an oral session. In a cohort of treatment-naïve patients with CLL, long-term safety and efficacy of assessment showed high response rates with no new safety signals identified. The median time on trial was 42 months, with 89% of patients remaining on treatment with Calquence at the time of analysis.2

John C. Byrd, MD, Distinguished University Professor, The Ohio State University, and Principal Investigator for the ACE-CL-001 CLL clinical trial, said: "A key challenge in the treatment of CLL is ensuring patients have therapies that they can tolerate and benefit from over the long term. The results seen in this patient cohort at 3.5 years of follow-up are encouraging for both durability of response and tolerability of therapy. We look forward to continued data from ongoing studies evaluating acalabrutinib in CLL."

Summary of key investigator-assesseda efficacy results from the Phase I/II open-label, single-arm ACE-CL-001 Calquence trial in 99 patients with CLL, evaluating the treatment-naïve cohort2:

Efficacy measure Result (N=99)
Overall response rate

(Complete response + partial response)

97%

Complete response

5%

Partial response

92%

Median duration of responseb

NR (range, 42.4 to NR)c

36 month duration of response rate (95% CI)b,d,e

98% (90, 99)

Median progression-free survival

NR (range, 44.2 to NR)c

36 month progression-free survival rate (95% CI)d,e

97% (91, 99)

a Response was assessed using International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria with modification for lymphocytosis.

b Only responders with ≥ partial response were included in this analysis.

c Not reached (NR).

d Confidence interval (CI).

e Based on the Kaplan-Meier estimates.

In this trial, the most common AEs (≥ 20%, all grades) were diarrhoea (49%), headache (44%), upper respiratory tract infection (40%), contusion (39%), arthralgia (33%), weight increased (31%), nausea (30%) and cough (23%). Grade 3/4 AEs (≥ 5%) were neutropenia (8%), hypertension (7%), diarrhoea (5%) and headache (5%). Atrial fibrillation and hypertension (all grades) occurred in 6% and 17% of patients, respectively, with Grade 3 events occurring in 2% and 7% of patients. Bleeding events (all grades) occurred in 64% of patients with contusion being most common (39%). All but three (3% Grade 3) bleeding events were Grade 1/2 events and no patients discontinued due to bleeding. Overall, 11% of patients discontinued treatment, 5% of which were due to AEs, including secondary malignancies (angiosarcoma, glioblastoma multiforme, small cell lung cancer), sepsis (Grade 4) and urinary tract infection (Grade 3). One Grade 5 event (multiorgan failure) in the setting of pneumonia was reported, which was considered unrelated to Calquence.2

NOTES TO EDITORS
About Calquence

Calquence (acalabrutinib) is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3 In B cells, BTK signalling results in activation of pathways necessary for B cell proliferation, trafficking, chemotaxis, and adhesion.3

Calquence was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Calquence is not currently licensed for the treatment of chronic lymphocytic leukaemia (CLL).

Calquence was granted Orphan Drug designation by the European Commission in 2016 and the US FDA in 2015 for the treatment of patients with CLL, MCL and Waldenstrom’s macroglobulinemia; and Breakthrough Therapy Designation in August 2017 by the US FDA for the treatment of patients with MCL who have received at least one prior therapy.

About mantle cell lymphoma (MCL)

MCL is an uncommon type of B-cell non-Hodgkin lymphoma.5,6,7 MCL comprises 3% to 6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it was estimated that approximately 3,300 new cases of MCL were diagnosed in 2016.5,8 The median age at diagnosis is 68 years,5 with MCL occurring more than twice as often in men than women.7 While MCL patients initially respond to treatment, there is a high relapse rate.5

About chronic lymphocytic leukaemia (CLL)

CLL is the most common type of leukaemia in adults and accounts for approximately one in four cases of leukaemia.9,10 The average age at the time of diagnosis is approximately 70 years of age.10 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.9 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.9 This could result in anaemia, infection and bleeding.9 B cell receptor signalling through BTK is one of the essential growth pathways for CLL

On December 3, 2018 NeoImmuneTech, Inc., an immunotherapy drug development company focused on advanced cancer treatments, reported the presentation of two preclinical studies supporting the potential of combining Hyleukin-7 with Universal CAR-T (UCART) treatment to enhance and prolong the activity of allogeneic "off-the-shelf" adoptive immunotherapy for the treatment of B cell and T cell lymphomas (Press release, NeoImmuneTech, DEC 3, 2018, View Source [SID1234531839]). The data were presented in an oral presentation and a poster session at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA.

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The two studies, conducted in collaboration with researchers from Washington University in St. Louis, evaluated the effects that Hyleukin-7, a long-acting T cell amplifier, had in combination with different types of UCART treatments. The researchers evaluated Hyleukin-7’s effects on proliferation, differentiation and tumor killing capacity of UCARTs in tumor models of B cell lymphoma and T cell lymphoma. The T cell lymphoma model was a physiologically-relevant patient-derived xenograft (PDX) mouse model of Sézary syndrome (SS), an aggressive and highly-morbid cutaneous T cell lymphoma with no widely-effective treatments.

Hyleukin-7 was shown to dramatically enhance UCART proliferation, persistence and tumor killing in vivo, resulting in enhanced survival in both models. Furthermore, the results suggest that the addition of Hyleukin-7 dramatically increased the activity of UCART treatment and could provide a tunable, clinic-ready "enabling therapy" for suboptimal CART activity in vivo.

"NeoImmuneTech’s Hyleukin-7 has broad potential to strengthen our immune system in its battle against both foreign invaders as well as enemies within, adding a therapeutic effect wherever the body’s T cells are weak or in low numbers," said Se Hwan Yang, Ph.D., Chief Executive Officer of NeoImmuneTech. "These latest experiments in lymphoma models show that Hyleukin-7 may also strengthen and prolong the effects of T cell therapies, such as CAR-T. The beneficial effects of Hyleukin-7 when combined with UCART are highly encouraging, as developing an effective, off-the-shelf and universal CAR-T therapeutic is a major goal for immuno-oncology drug developers. NeoImmuneTech’s main focus is advancing our clinical trials with Hyleukin-7 as efficiently as possible so that we can ultimately deliver it in a timely manner to patients in need."

Dr. John F. DiPersio, M.D., Ph.D., Chief, Division of Oncology and Deputy Director of the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine added: "CAR-T therapies hold a great promise for cancer patients, as well as for other diseases. We have made incredible steps toward creating a universal CAR-T that would highly increase the percent of people that can benefit from this technology, while significantly decreasing the time to treatment and the cost of production. However, a major hurdle that still remains for both current and future CAR-T treatments is the short effective period for these cells in the body. Hyleukin-7 has the potential to boost both the time and the effectivity of CAR-T treatments, and we are looking forward to the continued clinical development of this drug candidate."

Presentation Details:
Abstract number: 340
Title: Modeling Sézary Syndrome for Immunophenotyping and Anti-Tumor Effect of Ucart and Long-Acting Interleukin-7 Combination Therapy
Type: Oral presentation
Time: Sunday, December 2, 2018: 10:15 AM
Location: Room 28D (San Diego Convention Center)

Abstract number: 2199
Title: A Long-Acting Pharmacological Grade Interleukin-7 Molecule Logarithmically Accelerates Ucart Proliferation, Differentiation, and Tumor Killing
Type: Poster presentation
Time: Saturday, December 1, 2018, 6:15 PM-8:15 PM
Location: Hall GH (San Diego Convention Center)

About Hyleukin-7
Hyleukin-7 (rhIL-7-hyFc, NT-I7), an immuno-oncology agent, is a T cell amplifier comprising a covalently linked homodimer of engineered Interleukin-7 (IL-7) molecule, biologically fused with the proprietary long-acting platform – hyFc. IL-7 is known to be a critical factor for T cells, acting to increase both the number and functionality of T cells. Hyleukin-7 could play a pivotal role in reconstituting and reinvigorating T cell immunity in the treatment of patients with cancer and lymphopenia, as well as providing unique opportunities for immuno-oncology (IO) combination strategies. Hyleukin-7 is being developed as an "IO enabling" therapy to harness T cell immunity in combination with current cancer treatments such as anti-PD-(L)1 agents or chemo/radiotherapy. NeoImmuneTech and Genexine, Inc. (Genexine) are collaborating in three Phase 1b/2a clinical trials in advanced solid tumors and glioblastoma in the US and Korea.

On December 3, 2018 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported updated data from the Phase I trial (including an expansion cohort) evaluating IPH4102 in refractory patients with Sézary syndrome (SS) and its plan to advance IPH4102 in a multi-cohort Phase II study in different subtypes of T-cell lymphoma (Press release, Innate Pharma, DEC 3, 2018, View Source [SID1234531855]). An oral presentation will take place on Monday, December 3, at the ASH (Free ASH Whitepaper) 2018 Annual Meeting in San Diego, USA, by Pr Martine Bagot, Head of the Dermatology Department at the Saint Louis Hospital, Paris and Principal Investigator of the study. IPH4102 is Innate Pharma’s wholly-owned first-in-class anti-KIR3DL2 antibody, designed for treatment of T-cell lymphoma.

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As of October 15, 2018, data from the subgroup of 35 SS patients revealed strong clinical activity, demonstrated by an overall response rate (ORR) of 42.9%, median duration of response (DoR) of 13.8 months and median progression-free survival (PFS) of 11.7 months.

Mogamulizumab pretreated patients (n=7) showed an ORR (42.9%), median DoR (13.8 months) and median PFS (16.8 months) similar to the entire group. The ORR appeared to be higher (n = 28, 53.6%) in patients with no histologic evidence of large cell transformation (LCT*).

"The solid updated data on IPH4102 presented today strongly encourage us to advance IPH4102 in refractory Sézary syndrome patients. We believe that the planned Phase II study, together with the Phase I data, has the potential to support a BLA submission in this indication," commented Pierre Dodion, Chief Medical Officer of Innate Pharma. "In addition, the expression profile of KIR3DL2 provides a strong rational to explore the potential of IPH4102 in other subtypes of T-cell lymphomas in the TELLOMAK phase II study".

Importantly, clinical activity was associated with a substantial improvement in quality of life as assessed by the SkinDex29 and Pruritus Visual Analog Scale (VAS) scores. IPH4102 displayed a favorable safety profile, consistent with previous observations.

"Refractory Sézary syndrome patients have limited effective treatment options in later lines of therapy, with toxicity remaining an area of great concern with currently approved drugs," commented Professor Martine Bagot, Principal Investigator of the study. "IPH4102, in addition to demonstrating an impressive clinical activity, has shown a favorable safety profile and substantially improves the quality of life even in patients with stable disease. Translational results show relevant pharmacodynamics effects of IPH4102 in skin and in blood, which are in line with the clinical efficacy of the drug."

Exploratory biomarker analysis show early elimination of aberrant tumor cells and peripheral blood KIR3DL2+ CD4 T cells upon IPH4102 administration in responding patients.

The presentation is available in the IPH4102 section on Innate Pharma’s website.

KOL webcast and conference call on Tuesday, December 4, at 5pm CET (8am PST)

Pierre Dodion, Chief Medical Officer, Innate Pharma, will be joined by Prof. Martine Bagot, Head of Dermatology Department at the Saint Louis Hospital, Paris and lead investigator of the study, for a live webcast and conference call with a Q&A session on Tuesday, December 4 at 5pm CET to discuss the announcement.

The presentation and access to the live webcast will be available at this link: View Source

Participants can also join the conference call using the following dial-in numbers:

Location

Purpose

Phone number

France

Participant

+33 (0)1 76 77 22 57

United Kingdom

Participant

+44 (0)330 336 9411

United States

Participant

+1 929-477-0324

Standard International Access

Participant

0800 279 7204

The participation code is: 4535688