On December 7, 2020 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ:MOR) and Incyte (Nasdaq:INCY) reported that preliminary data from firstMIND, the ongoing Phase 1b, open-label, randomized study on the safety and efficacy of tafasitamab or tafasitamab plus lenalidomide in addition to R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were presented today during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) (Press release, MorphoSys, DEC 7, 2020, View Source [SID1234572329]). Additionally, a long-term subgroup analysis of the L-MIND study investigating tafasitamab combined with lenalidomide in patients with relapsed or refractory DLBCL was also presented at ASH (Free ASH Whitepaper).

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The preliminary results of firstMIND indicate that tafasitamab plus lenalidomide in addition to R-CHOP shows an acceptable tolerability profile. Toxicities appear to be similar to what is expected with R-CHOP alone or in combination with lenalidomide. Serious or severe neutropenia and thrombocytopenia events (grade 3 or higher) were more frequent in the tafasitamab plus lenalidomide arm. The incidence of febrile neutropenia was comparable between both arms and the average relative dose intensity of R-CHOP was maintained in both arms. Interim response assessments after three cycles were available for 45 patients. In both arms combined, 41/45 (91.1%) of patients had an objective response as per Lugano 2014.1

The preliminary data from this ongoing study in first-line DLBCL warrant further investigation. To that end, MorphoSys and Incyte plan to initiate frontMIND, a Phase 3 trial evaluating tafasitamab plus lenalidomide in combination with R-CHOP compared to R-CHOP alone as first-line treatment for patients with newly diagnosed DLBCL.

"The preliminary firstMIND study results mark another important step as we explore the potential of tafasitamab as a backbone therapy," said Dr. Malte Peters, Chief Research and Development Officer at MorphoSys. "Given the data available to date, including data from the L-MIND study, we believe that the mechanism of action, efficacy and safety profile of tafasitamab have the potential to make it a preferred combination partner as we seek to transform the standard of care in DLBCL. We are committed to developing innovative therapies to battle this aggressive disease for the benefit of patients with DLBCL, and look forward to beginning the planned frontMIND in the first half of 2021."

"The initial results of the firstMIND study, shared today at ASH (Free ASH Whitepaper), as well as the long-term analyses from L-MIND, underscore the potential of tafasitamab as a combination therapeutic for patients with DLBCL, where there remains a significant unmet need. Along with our partners at MorphoSys, we are pleased to be moving forward with the initiation of a Phase 3 study in 2021," said Steven Stein, M.D., Chief Medical Officer at Incyte.

In addition to the firstMIND data presented today, the long-term L-MIND analyses showed that treatment with tafasitamab plus lenalidomide resulted in durable responses after >=2 years of follow-up. At the time of analysis, patients with complete responses (CR) continued to experience durable treatment responses, including long duration of response (DoR) and overall survival (OS). The data also showed that tafasitamab plus lenalidomide taken for 12 cycles, followed by tafasitamab until progression, did not result in any unexpected safety signals.2

In July 2020, the FDA approved Monjuvi(R) (tafasitamab-cxix), a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).3

The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)
DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide4, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter5. In the United States each year, approximately 10,000 patients are diagnosed with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant (ASCT).6,7,8

About firstMIND
The firstMIND (NCT04134936) trial is a Phase 1b, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The study includes a safety run-in phase and a main phase. In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include objective response rate, PET negative complete response (PET-CR) rate at end of treatment, progression-free survival, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab.

About Tafasitamab
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(R) (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi(R) is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

A marketing authorization application (MAA) seeking the approval of tafasitamab in combination with lenalidomide in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi(R) is a registered trademark of MorphoSys AG.
XmAb(R) is a registered trademark of Xencor, Inc.

Important Safety Information
What are the possible side effects of MONJUVI?
MONJUVI may cause serious side effects, including:

– Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.

– Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or any bruising or bleeding.

– Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or develop any signs and symptoms of an infection.

The most common side effects of MONJUVI include:

– Feeling tired or weak

– Diarrhea

– Cough

– Fever

– Swelling of lower legs or hands

– Respiratory tract infection

– Decreased appetite

These are not all the possible side effects of MONJUVI.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

– Have an active infection or have had one recently.

– Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

– You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.

– Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.

– Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.

You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On December 7, 2020 AstraZeneca reported that A pooled analysis of cardiovascular (CV) safety data from 762 patients treated with Calquence (acalabrutinib) monotherapy for chronic lymphocytic leukaemia (CLL), the most common type of adult leukaemia, across four clinical trials showed a low incidence of cardiac adverse events (AEs) leading to discontinuation (Press release, AstraZeneca, DEC 7, 2020, View Source [SID1234572328]).1,2 These results were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on 7 December 2020.

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The analysis included patients with previously untreated and relapsed or refractory CLL treated with Calquence alone from the ELEVATE TN and ASCEND Phase III trials, as well as the 15-H-0016 Phase II trial and ACE-CL-001 Phase I/II trial. In the analysis, 129 patients (17%) reported a cardiac AE of any grade at a median follow up of 25.9 months, and seven patients (0.9%) discontinued treatment due to cardiac AEs.1

Jennifer Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, and principal investigator, said: "Cardiac adverse events have emerged as an important consideration for treating chronic lymphocytic leukaemia patients with Bruton’s tyrosine kinase inhibitors, as cardiovascular complications have become a frequent reason for discontinuation. The data presented in this study suggests a low risk of cardiac adverse events with acalabrutinib that is similar to those in a general population of untreated patients with chronic lymphocytic leukaemia, giving clinicians further reassurance when prescribing this therapy."

José Baselga, Executive Vice President, Oncology R&D, said: "These combined results across four of our clinical trials reinforce the cardiovascular safety profile of Calquence for the treatment of chronic lymphocytic leukaemia. With Calquence, we aim to selectively target Bruton’s tyrosine kinase to help improve safety and long-term adherence while maintaining outstanding efficacy."

Median exposure to Calquence was 24.9 months. Cardiac events that occurred in 2% or more of patients included atrial fibrillation (4%), atrial fibrillation/flutter (5%), palpitations (3%) and tachycardia (2%). The incidence of atrial fibrillation was similar to that in a general, previously untreated CLL patient population (6%).1,3

Grade 3 or higher cardiac AEs occurred in 37 patients (4%) treated with Calquence monotherapy, of which 25% were reported during the first six months of treatment. Grade 3 or higher cardiac AEs of interest included atrial fibrillation (1.3%), complete atrioventricular (AV) block (0.3%), acute coronary syndrome (0.1%), atrial flutter (0.1%), second degree AV block (0.1%) and ventricular fibrillation (0.1%). Two patients experienced Grade 5 AEs (one with congestive heart failure and one with heart attack).1

Overall, 91% of patients with cardiac AEs versus 79% patients without cardiac AEs had one or more CV risk factors before receiving Calquence. The most prevalent CV risk factors (greater than or equal to 20% of patients) among those who experienced cardiac AEs were hypertension (67%), hyperlipidemia (29%) and arrhythmias (22%).1

AstraZeneca is exploring additional trials in CLL, including the ELEVATE-RR Phase III trial (ACE-CL-006) evaluating Calquence versus ibrutinib in patients with previously treated high-risk CLL. Data is anticipated in 2021.

Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults, with an estimated 105,000 new cases globally in 2016, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.2,4,5,6 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.4 B-cell receptor signalling through Bruton’s tyrosine kinase (BTK) is one of the essential growth pathways for CLL.

Calquence

Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.7,8 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.7

Calquence is approved for the treatment of CLL and small lymphocytic lymphoma in the US and is approved for CLL in the EU and several other countries worldwide. Calquence is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in the US and several other countries.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, follicular lymphoma, and other haematologic malignancies.

AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two medicines approved by the US Food and Drug Administration and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On December 7, 2020 Incyte (Nasdaq:INCY) and MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ:MOR) reported that preliminary data from firstMIND, the ongoing Phase 1b, open-label, randomized study on the safety and efficacy of tafasitamab or tafasitamab plus lenalidomide in addition to R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were presented today during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) (Press release, Incyte, DEC 7, 2020, View Source [SID1234572327]). Additionally, a long-term subgroup analysis of the L-MIND study investigating tafasitamab combined with lenalidomide in patients with relapsed or refractory DLBCL was also presented at ASH (Free ASH Whitepaper).

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The preliminary results of firstMIND indicate that tafasitamab plus lenalidomide in addition to R-CHOP shows an acceptable tolerability profile. Toxicities appear to be similar to what is expected with R-CHOP alone or in combination with lenalidomide. Serious or severe neutropenia and thrombocytopenia events (grade 3 or higher) were more frequent in the tafasitamab plus lenalidomide arm. The incidence of febrile neutropenia was comparable between both arms and the average relative dose intensity of R-CHOP was maintained in both arms. Interim response assessments after three cycles were available for 45 patients. In both arms combined, 41/45 (91.1%) of patients had an objective response as per Lugano 20141.

The preliminary data from this ongoing study in first-line DLBCL warrant further investigation. To that end, MorphoSys and Incyte plan to initiate frontMIND, a Phase 3 trial evaluating tafasitamab plus lenalidomide in combination with R-CHOP compared to R-CHOP alone as first-line treatment for patients with newly diagnosed DLBCL.

"The initial results of the firstMIND study, shared today at ASH (Free ASH Whitepaper), as well as the long-term analyses from L-MIND, underscore the potential of tafasitamab as a combination therapeutic for patients with DLBCL, where there remains a significant unmet need. Along with our partners at MorphoSys, we are pleased to be moving forward with the initiation of a Phase 3 study in 2021," said Steven Stein, M.D., Chief Medical Officer at Incyte.

"The preliminary firstMIND study results mark another important step as we explore the potential of tafasitamab as a backbone therapy," said Dr. Malte Peters, Chief Research and Development Officer at MorphoSys. "Given the data available to date, including data from the L-MIND study, we believe that the mechanism of action, efficacy and safety profile of tafasitamab have the potential to make it a preferred combination partner as we seek to transform the standard of care in DLBCL. We are committed to developing innovative therapies to battle this aggressive disease for the benefit of patients with DLBCL, and look forward to beginning the planned frontMIND in the first half of 2021."

In addition to the firstMIND data presented today, the long-term L-MIND analyses showed that treatment with tafasitamab plus lenalidomide resulted in durable responses after ≥2 years of follow-up. At the time of analysis, patients with complete responses (CR) continued to experience durable treatment responses, including long duration of response (DoR) and overall survival (OS). The data also showed that tafasitamab plus lenalidomide taken for 12 cycles, followed by tafasitamab until progression, did not result in any unexpected safety signals2.

In July 2020, the FDA approved Monjuvi (tafasitamab-cxix), a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)3.

The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide4, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter5. In the United States each year, approximately 10,000 patients are diagnosed with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant (ASCT)6,7,8.

About firstMIND

The firstMIND (NCT04134936) trial is a Phase 1b, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The study includes a safety run-in phase and a main phase. In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include objective response rate, PET negative complete response (PET-CR) rate at end of treatment, progression-free survival, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab.

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

A marketing authorization application (MAA) seeking the approval of tafasitamab in combination with lenalidomide in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi is a registered trademark of MorphoSys AG.

XmAb is a registered trademark of Xencor, Inc.

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.
The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands
Respiratory tract infection
Decreased appetite
These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.
You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.
Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.
You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On December 7, 2020 Incyte (Nasdaq:INCY) reported data from three ongoing Phase 2 studies evaluating parsaclisib, a potent, highly selective, next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), for the treatment of patients with relapsed or refractory follicular (CITADEL-203), marginal zone (CITADEL-204) and mantle cell (CITADEL-205) lymphomas (Press release, Incyte, DEC 7, 2020, View Source [SID1234572326]). These data were accepted for presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2020), held virtually from December 5–8, 2020.

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The primary endpoint for the CITADEL-203, -204 and -205 studies is objective response rate (ORR); duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and tolerability are among the secondary endpoints. All radiology-based endpoints are based on independent review committee (IRC) assessment.

Eligible patients received parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and patients initially enrolled in the WG were allowed to switch to DG. Data are presented for the DG and all patients.

Key results from the CITADEL studies include:

ORR (95% CI), %

mDOR (95% CI),

months

mPFS (95% CI),

months

mOS (95% CI),

months

CITADEL-203: R/R Follicular Lymphoma

DG (N=95)

75 (65-83)

14.7 (12.0-17.5)

15.8 (13.8-19.1)

–

All (N=118)

73 (64-81)

15.9 (12.0-NE)

15.8 (13.2-19.3)

–

CITADEL-204: R/R Marginal Zone Lymphoma

DG (N=72)

56.9 (44.7-68.6)

NR (8.1-NE)

NR (11.0-NE)

–

All (N=100)

57.0 (46.7-66.9)

12.0 (9.3-NE)

19.4 (13.7-NE)

–

CITADEL-205: R/R Mantle Cell Lymphoma (BTK Inhibitor Treatment Naive)

DG (N=77)

71 (60-81)

9.0 (6.7-14.7)

11.1 (8.3-NE)

NR (NE-NE)

All (N=108)

70 (61-79)

14.7 (7.7-NE)

11.1 (8.3-19.2)

NR (NE-NE)

CITADEL-205: R/R Mantle Cell Lymphoma (Previously Treated with Ibrutinib)

DG (N=41)

29 (16-46)

3.7 (1.9-NE)

3.7 (1.8-4.1)

11.2 (7.9-NE)

All (N=53)

25 (14-38)

3.7 (1.9-NE)

3.7 (1.8-3.9)

11.2 (7.9-17.1)

R/R: relapsed or refractory; ORR: objective response rate; mDOR: median duration of response (reported for responders); mPFS: median progression-free survival; mOS: median overall survival; DG: daily dosing group; BTK: Bruton’s tyrosine kinase.

Parsaclisib was generally well tolerated in all studies with a manageable safety profile.

"Data from the CITADEL studies presented at ASH (Free ASH Whitepaper) 2020 are very promising and they highlight the potential of parsaclisib to become a meaningful treatment for patients with relapsed or refractory follicular, marginal zone or mantle cell lymphomas," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "We look forward to continuing our work as we seek to bring this medicine to patients."

Presentations are available on the ASH (Free ASH Whitepaper) website at View Source; #338 (Oral presentation, CITADEL-204), #2935 (Poster, CITADEL-203), #1121 (Poster, CITADEL-205), #2044 (Poster, CITADEL-205).

About Follicular, Marginal Zone and Mantle Cell Lymphomas

Non-Hodgkin lymphoma (NHL) is a type of cancer that starts in the lymphocytes, a type of white blood cell. Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) are forms of B-Cell NHLs. FL and MZL are indolent or slow growing lymphomas; MCL is an aggressive or rapidly developing form. There is an unmet medical need for treatment options for patients who are relapsed or refractory to initial therapies.

About CITADEL

The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is evaluating parsaclisib in several ongoing studies as a treatment for adult patients with lymphomas, including:

CITADEL-203 (NCT03126019) is evaluating patients with relapsed or refractory follicular lymphoma (FL) Grade 1, 2 or 3a who received at least two prior systemic therapies, had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and were ineligible for hematopoietic stem cell transplantation (HSCT).
CITADEL-204 (NCT03144674) is evaluating patients with relapsed or refractory marginal zone lymphoma (MZL) who received at least one prior systemic therapy and were Bruton’s tyrosine kinase (BTK) inhibitor treatment naive. Patients with prior ibrutinib treatment were initially allowed to enroll; however, the cohort was terminated due to slow enrollment. Eligible patients had radiologically measurable lymphadenopathy or extranodal lymphoid malignancy (or histologically confirmed bone marrow infiltration in cases of splenic MZL), and an ECOG PS ≤2.
CITADEL-205 ( NCT03235544 ) is evaluating patients with relapsed or refractory mantle cell lymphoma (MCL), who received one to three prior systemic therapies and were either naive to or were previously treated with a BTK inhibitor. Eligible patients had an ECOG PS ≤2, and radiologically measurable lymphadenopathy or extranodal lymphoid malignancy.
Patients eligible for each trial were allocated to receive parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and the WG patients were allowed to switch to DG. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required.

About Parsaclisib

Parsaclisib is a potent, highly selective, next-generation investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). It is currently under evaluation as a monotherapy in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell); and autoimmune hemolytic anemia. Pivotal trials of parsaclisib in combination with ruxolitinib for the treatment of patients with myelofibrosis are underway; and there are plans to initiate a trial to evaluate parsaclisib in combination with tafasitamab for B-cell malignancies.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates, including parsaclisib. Under the terms of the agreement, Innovent has received the rights to develop and commercialize parsaclisib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.

Conference Call Information

Incyte will host an investor conference call and webcast at 10:00 a.m. ET (7:00 a.m. PT) today, December 7, 2020—the call and webcast can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 90 days.

On December 7, 2020 Sierra Oncology, Inc. (SRRA), a late-stage biopharmaceutical company on a quest to deliver targeted therapies that treat rare forms of cancer, reported an updated efficacy analyses of momelotinib in myelofibrosis patients with thrombocytopenia (Press release, Sierra Oncology, DEC 7, 2020, View Source [SID1234572324]). The data were presented in a poster presentation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Jean-Jacques Kiladjian, MD, PhD, Consultant Hematologist, Head, Clinical Investigation Center, Saint Louis Hospital, Paris, France.

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"This retrospective analysis of the two Phase 3 SIMPLIFY studies demonstrate that the relative benefit-risk profile of momelotinib and ruxolitinib is influenced by baseline platelet count. What we show in this analysis is that momelotinib’s safety and activity profile do not appear to be affected by baseline platelet count, while in contrast, activity with ruxolitinib declined in patients with lower baseline platelet counts," said Dr. Kiladjian. "These updated data analyses complement previous findings that demonstrate the ability to initiate and maintain near-maximal momelotinib dose intensity regardless of baseline platelet count, suggesting that this durable dosing contributes to its efficacy profile."

"These exciting data provide a novel insight into a patient population where momelotinib’s unique receptor inhibition profile—JAK1, JAK2 & ACVR1—may be particularly relevant. The observation of preserved activity in patients with reduced platelet counts is provocative and potentially differentiating. The wealth of information contained in the SIMPLIFY studies will enable further analyses and potentially identify additional populations of interest to be presented at future scientific meetings," said Stephen Dilly, MBBS, PhD, Chief Executive Officer at Sierra Oncology. "We now look forward to completing enrollment in the pivotal Phase 3 MOMENTUM study and subsequent topline data to support our plan to file for regulatory approval of momelotinib for the treatment of myelofibrosis."

Momelotinib’s Spleen, Symptom and Anemia Efficacy is Maintained in Intermediate/High Risk Myelofibrosis Patients with Thrombocytopenia (Abstract #3086)

Dr. Kiladjian presented comparative efficacy data for momelotinib and ruxolitinib in patients with low platelets from the SIMPLIFY-1 (S1) and SIMPLIFY-2 (S2) Phase 3 studies. Results from the updated analyses include:

In S1 (JAKi-naïve), patients whose baseline platelet counts were:
<150 x 109/L, momelotinib achieved substantially higher TI (62% vs. 42%) and splenic response rates (23% vs. 4%) and a similar symptomatic response (28% vs. 33%) relative to ruxolitinib
150-300 x 109/L, generally similar splenic (35% vs. 32%) and symptom response rates (33% vs. 41%) and a higher TI response rate (72% vs. 54%) were achieved with momelotinib relative to ruxolitinib
>300 x 109/L, ruxolitinib achieved higher splenic (44% vs. 19%) and symptom response rates (46% vs. 23%) at week 24 than with momelotinib; the Week 24 TI rate remained higher with momelotinib (63% vs. 51%)
In S2 (JAKi-exposed patients):
Momelotinib’s response rates for the 3 response parameters remain very consistent with overall ITT response rates in patients whose baseline platelets were <150 x 109/L
Momelotinib’s symptomatic and anemia benefit were also preserved in patients whose baseline platelet counts were <50 and >50-100 x 109/L
In both S1 and S2, rates of TEAEs on momelotinib were generally similar between the overall safety population and subjects with baseline platelets <150 x 109/L
Patients were randomized 1:1 (S1) and 2:1 (S2) to receive momelotinib (200 mg QD) versus ruxolitinib (20 mg BID) or best available therapy (88.5% RUX/RUX+) for 24 weeks followed by extended momelotinib treatment. A baseline platelet limit of >50 x 109/L was required in S1 while there was not lower platelet limit for S2. Both trials had primary endpoints of Splenic Response Rate and secondary endpoints of Total Symptom Score and Transfusion Independence Rate.

About Momelotinib

Momelotinib is a selective and orally bioavailable JAK1, JAK2 and ACVR1 inhibitor currently under investigation for the treatment of myelofibrosis. Myelofibrosis results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia.

Momelotinib is currently under investigation in the MOMENTUM clinical trial, a global, randomized, double-blind Phase 3 study for symptomatic and anemic myelofibrosis patients. Top-line data are anticipated in H1 2022. The U.S. Food & Drug Administration has granted Fast Track designation for momelotinib.