On December 11, 2021 City of Hope reported that data from an investigational Phase 1/2, single arm trial using a bispecific antibody called mosunetuzumab highlights the paradigm-changing potential of a new treatment option for people with follicular lymphoma, a type of blood cancer and the most common indolent form of non-Hodgkin lymphoma (NHL) (Press release, City of Hope, DEC 11, 2021, View Source [SID1234596848]). Patients within the trial achieved high response rates with 80% of patients responding positively to the treatment, and 60% had a complete response, meaning the cancer could not be detected.

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"Our study demonstrated that an antibody based on bispecific T cell engaging technology is proving to work very well with high response rates — and safely — in blood cancer patients who need more effective therapies and with fewer side effects," said Elizabeth Budde, M.D., Ph.D., associate professor, City of Hope Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, who discussed the results today at an ASH (Free ASH Whitepaper) press briefing. "Mosunetuzumab is a very promising therapy, showing deep and durable responses for patients whose lymphoma has relapsed or is no longer responding to currently available therapies."

Instead of concentrating on a singular target, "bispecific" antibodies are therapeutics that act on two cellular targets simultaneously. In the case of mosunetuzumab, one "arm" targets the CD3 protein on T cells, an immune cell that can help in the fight against cancer if engaged; a second "arm" binds to CD20, a protein commonly found on lymphoma cells.

"The two cell groups are pulled together, with mosunetuzumab serving as a kind of bridge," Budde said. "Being in such close proximity allows the now activated T cells to better recognize and attack the lymphoma cells."

Ninety patients with follicular lymphoma, who ranged in age from 29 to 90 years old, were enrolled in the multicenter international trial. The patients received mosunetuzmab, a Genentech medicine, intravenously every 21 days for a minimum of eight cycles and up to 17 cycles.

The median time to first response was 1.4 months. With a median follow up of 17.8 months, 70% patients with response continued to do well.

Cytokine release syndrome was a side effect in 44% of patients. Most were low grade and occurred during the first cycle. All resolved completely. Other side effects included fatigue and headache. Only two patients discontinued treatment due to mosunetuzumab-related side effects.

Genentech, a member of the Roche Group, plans to submit this new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be the first CD20xCD3 T cell engaging bispecific antibody approved for NHL.

Renee Bentson, 69, of Covina, California, was one of the first participants in the trial at City of Hope. Before she was diagnosed with cancer, Bentson, who was physically active and running seven miles a day, began to notice a rash, chest pain and night sweats. When an unusual fatigue set in and lumps began to appear, first on one side of her torso, then the other and on one arm, Bentson consulted a doctor, who promptly ordered a biopsy.

Bentson was diagnosed with follicular lymphoma, which makes up about 20% of all lymphoma cases. It tends to strike older people, and though it does respond to initial treatment, it is not curable with convention therapy and relapse is frequent. Remission duration tends to get shorter with each subsequent relapse after treatment.

While some patients do well on chemotherapy, Bentson was concerned about the potential side effects. She participated in a series of immunotherapy clinical trials. The cancer would shrink, but not disappear, and later it would recur. With mosunetuzumab, which was her fourth line of treatment, the cancer went into remission in early 2017 and she has been cancer free since then.

"I’m just so grateful that it worked," said Bentson, who experienced few side effects from the treatment.

City of Hope is a leader in blood cancer immunotherapies. The National Cancer Institute-designated comprehensive cancer center has performed more than 17,000 bone marrow/stem cell transplants and is a leader in chimeric antigen receptor (CAR) T therapy, with nearly 800 patients treated with immune effector cells, including CAR T therapy, and nearly 80 open or completed trials.

On December 11, 2021 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new pivotal data on its CD20xCD3 T-cell engaging bispecific antibody, mosunetuzumab, will be presented for the first time at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition from December 11-14, 2021 (Press release, Genentech, DEC 11, 2021, View Source [SID1234596847]).

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Emerging data continue to show the promising benefit-risk profile of mosunetuzumab in relapsed or refractory (R/R) follicular lymphoma (FL), a slow-growing, or indolent, form of non-Hodgkin’s lymphoma (NHL). Pivotal results from the Phase I/II GO29781 study demonstrated that mosunetuzumab induces durable complete responses lasting at least 18 months in heavily pretreated patients with R/R FL who have received two or more prior therapies, with a 60.0% complete response (CR) rate and a median progression-free survival of 17.9 months (95% CI: 10.1-not evaluable). Median duration of response was 22.8 months among responders (95% CI: 9.7-not evaluable). The most common adverse event (AE) was cytokine release syndrome (CRS), which was generally low grade (mainly Grade 1-2).

"Despite initial successful treatment, many people with follicular lymphoma often experience relapse. Mosunetuzumab could potentially become a highly efficacious treatment option that can be administered without the need for cell collection or genetic engineering," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "With mosunetuzumab, we also aim to offer a therapy that can be administered in the outpatient setting to people with this devastating blood cancer."

Genentech plans to submit the new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL. Roche recently submitted the initial marketing authorization application for mosunetuzumab to the European Medicines Agency, with the hope to bring this drug as soon as possible to people with NHL.

Additionally, as part of Genentech’s broad pipeline of hematology immunotherapies and application of novel combinations, key data for the bispecific antibodies mosunetuzumab, glofitamab and cevostamab are being presented, including:

Initial results from the Phase Ib CO41942 study of mosunetuzumab in combination with lenalidomide in people with R/R FL who have received at least one prior line of therapy demonstrated encouraging preliminary efficacy and a tolerable safety profile.
Data from the Phase Ib/II GO40516 study evaluating mosunetuzumab in combination with Polivy (polatuzumab vedotin-piiq) showed promising efficacy and favorable safety in heavily pretreated patients with aggressive R/R NHL with an objective response rate (ORR) of 65.0% and a CR rate of 48.3%. CRS occurred in 18% of patients, and all events occurred in Cycle 1 and were Grade 1-2.
A Phase I/Ib NP30179 dose-escalation study evaluating glofitamab as a monotherapy and in combination with Gazyva (obinutuzumab) following pretreatment with Gazyva in patients with R/R B-cell NHL showed promising activity in both R/R FL and R/R mantle cell lymphoma (MCL), an uncommon but aggressive form of lymphoma with poor prognosis for those who progress.
Preliminary results in heavily pretreated patients with R/R FL showed high response rates across all treatment groups, including high-risk subgroups, with an ORR of 81.0% for the glofitamab monotherapy group and an ORR of 100% for the glofitamab plus Gazyva combination therapy group. For patients with R/R MCL treated with glofitamab monotherapy following Gazyva pretreatment, the ORR was 81.0%. Across both studies, the most common AE was CRS, with the majority of events being low grade (Grade 1-2).
Results of the Phase Ib/II NP39488 study of glofitamab in combination with Polivy demonstrated encouraging preliminary efficacy and a tolerable safety profile in people with difficult-to-treat R/R diffuse large B-cell lymphoma. With a median follow up of 3.2 months (95% CI: 1.4-3.5), an ORR of 73.0% was observed with a 51.5% CR rate, with patients showing durable responses at ≥6 months. No Grade 3 or higher CRS events were observed, and the safety profile of the combination was consistent with that of the individual medicines.
Data from the Phase I GO39775 dose-escalation and expansion study investigating cevostamab in heavily pretreated patients with R/R multiple myeloma (MM) showed the first-of-its kind FcRH5xCD3 bispecific antibody induced clinically meaningful, target dose-dependent increases in ORR without an increase in the rate of CRS, with an ORR of 54.5% in the 160 mg dose group. Results from double step-up dosing suggest this approach could help mitigate CRS and potentially improve the safety profile compared to single step-up dosing.
Our investigational cancer immunotherapies, mosunetuzumab and glofitamab, are T-cell engaging bispecific antibodies designed to engage with CD3 on the T cell and CD20 on the tumor cell, bringing them close in proximity and enabling the T cell to eliminate the tumor cell. Although these bispecific antibodies have similar modes of action, they differ in their structure and clinical profiles. Cevostamab, another investigational T-cell engaging bispecific antibody, is designed to target FcRH5 on myeloma cells and CD3 on T cells and is currently being evaluated in people living with R/R MM.

Genentech’s broad and comprehensive clinical development program will continue to evaluate mosunetuzumab, glofitamab and cevostamab as monotherapies and in combination with other established and/or novel therapies for malignant hematological conditions with the goal of providing treatment solutions tailored to the patient journey for each disease.

Keep up to date with ASH (Free ASH Whitepaper) 2021 news and updates by using the hashtag #ASH21 and follow Genentech on Twitter via @Genentech and on LinkedIn.

About Genentech’s Investigational Bispecifics in Hematology

Genentech is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Genentech as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximize potential clinical benefits for patients. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format which we call ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions that bind to CD20 and one ‘Fab’ region that binds to CD3. The clinical development programs for mosunetuzumab and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines for the treatment of people with CD20-positive B cell (non-Hodgkin’s lymphomas), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

About Cevostamab (FcRH5xCD3 Bispecific Antibody)

Cevostamab (BFCR4350A) is an FcRH5xCD3 T-cell engaging bispecific antibody designed to target FcRH5 on myeloma cells and CD3 on T cells. FcRH5 is a unique and differentiated target, expressed on nearly all myeloma cells. Cevostamab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets FcRH5 and the other ‘Fab’ region targets CD3. This dual targeting activates and re-directs a patient’s existing T cells to engage and eliminate target FcRH5-expressing myeloma cells by releasing cytotoxic proteins into the myeloma cells.

About the GO29781 Study

The GO29781 study [NCT02500407] is a Phase I/II, multicenter, open-label, dose-escalation study evaluating the safety and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include complete response rate (best response) by independent review facility (primary endpoint), objective response rate, duration of response, progression-free survival, and safety and tolerability (secondary endpoints).

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information for additional Important Safety Information.

Gazyva U.S. Indication

Gazyva is a prescription medicine used with the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.

Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life-threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If a patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. If a patient has a weakened immune system, it could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems
Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must contact their healthcare team if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past
Additional possible serious side effects of Gazyva:

Patients must tell their healthcare team right away about any side effect they experience. Gazyva can cause side effects that may become severe or life-threatening, including:

Infusion-related reactions (IRRs): These side effects may occur during or within 24 hours of any Gazyva infusion. Some IRRs can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening IRRs. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the IRR is life-threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of IRRs may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort
Hypersensitivity reactions including serum sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva
Tumor lysis syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness
Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone, are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP
Low white blood cell count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections
Low platelet count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced
The most common side effects seen with Gazyva in a study that included relapsed or refractory FL patients were infusion-related reactions, fatigue, low white blood cell counts, cough, upper respiratory tract infection, and joint or muscle pain.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines
Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, or plan to become pregnant. Gazyva may harm a patient’s unborn baby. The patient should speak to their healthcare team about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. Women of childbearing potential should use effective contraception while taking Gazyva and for 6 months after their Gazyva treatment
Breastfeeding: Because of the potential risk of serious side reactions in breastfed children, women should not breastfeed while taking Gazyva and for 6 months after their last dose
Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source

On December 11, 2021 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported the presentation of preclinical data on NL-201 in multiple myeloma at the 63RD American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place virtually and in person December 11-14, 2021 (Press release, Neoleukin Therapeutics, DEC 11, 2021, View Source [SID1234596845]). Additionally, a published abstract in Blood reports on NL-201 antitumor activity in preclinical studies of non-Hodgkin lymphoma.

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NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without a bias toward cells expressing the IL-2 receptor alpha subunit (CD25). NL-201 is currently in a Phase 1 clinical trial for patients with solid tumors.

The preclinical multiple myeloma data, to be presented in a poster session by Simone A. Minnie, PhD, Fred Hutchinson Cancer Research Center, demonstrate the ability of NL-201 to prevent relapse in murine myeloma models following autologous stem cell transplant. Experimental results indicate that anti-myeloma activity is mediated by expansion of cytotoxic memory CD8 T cells and a decrease in T-regulatory CD4 cells in the bone marrow. Furthermore, NL-201 treated mice had an increase in bone marrow T-cells expressing granzyme B and a decrease in the T-cell exhaustion phenotype.

"These data, generated by our collaborators at the Fred Hutchinson Cancer Research Center, demonstrate robust immune effects and anti-myeloma activity in a challenging setting," said Priti Patel M.D., Chief Medical Officer of Neoleukin. "Together with our published results on the preclinical activity of NL-201 against B-cell lymphoma, we believe that a clinical trial of NL-201 in patients with hematologic malignancies is warranted. We expect to initiate a Phase 1 trial in 2022 to evaluate NL-201 in patients with these indications."

Further details as follows:

Abstract number: 1609
The IL-2/IL-15 Mimetic NL-201 Prevents Myeloma Relapse after ASCT by Expanding Highly Cytolytic T Cells in the Bone Marrow that are Resistant to Exhaustion

Abstract number: 4560
NL-201, a De Novo Agonist of IL-2 and IL-15 Receptors, Demonstrates Synergistic Antitumor Activity with Anti-PD-1 Checkpoint Inhibitor Therapy in a Preclinical Non-Hodgkin Lymphoma Model

The ASH (Free ASH Whitepaper) poster and abstract link are available on the Neoleukin website publications page: View Source

About NL-201
NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at low doses with minimal impact on immunosuppressive regulatory T cells. Furthermore, NL-201 has demonstrated both monotherapy and combination activity across a wide range of preclinical syngeneic tumor models.

On December 11, 2021 Novartis reported new 48-week data from the Phase III ASCEMBL trial of Scemblix (asciminib) demonstrating that the results observed in the primary analysis (24 weeks) vs. Bosulif* (bosutinib) were maintained in longer-term follow up for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs)1-4 (Press release, Novartis, DEC 11, 2021, View Source [SID1234596843]).

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In this analysis, presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper), the major molecular response (MMR) rate at 48 weeks was 29.3% for patients treated with Scemblix vs. 13.2% for patients in the Bosulif arm, which is consistent with a doubling of the efficacy at 24 weeks (25% vs. 13% [P=0.029])1-4. The proportion of patients treated with Scemblix who experienced adverse reactions leading to discontinuation was more than three times lower than those in the Bosulif arm (7.1% vs. 25%)1.

Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket2. This novel mechanism of action, also known in scientific literature as a STAMP inhibitor, can help address resistance to TKI therapy in patients with CML and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells2-4. Scemblix continues to be studied across multiple lines of treatment for CML-CP3-12.

"We often see that sequential use of TKI treatments can be associated with increased failure rates and greater concerns regarding potential treatment side effects as patients move to later lines. Scemblix offers an increasingly proven option for patients living with CML who have previously tried two or more TKIs, and takes a different approach to targeted inhibition to better manage CML," said Dr. Michael J. Mauro**, Hematologist and Myeloproliferative Neoplasms Program Leader at Memorial Sloan Kettering Cancer Center (MSK).

In this updated analysis, responses were also durable, with 60 out of 62 patients on Scemblix maintaining MMR at time of their last assessment1. Scemblix continued to deliver more favorable deep molecular responses (MRs) with MR4 and MR4.5 rates at 48 weeks of 10.8% and 7.6%, compared to 3.9% and 1.3% in patients treated with Bosulif, respectively1. Additionally, the cumulative proportion of patients achieving a level of BCR-ABL1IS ≤1% at 48 weeks – a predictor of better long-term outcomes in this heavily pretreated patient population – was higher in the Scemblix arm than in the Bosulif arm (50.8% vs 33.7%)1.

The most common reason for treatment discontinuation was lack of efficacy in 37 (23.6%) patients treated with Scemblix and 27 (35.5%) patients treated with Bosulif1. Median duration of exposure was 15.4 months (range, 0.0–37.3 months) for Scemblix and 6.8 months (range, 0.2–34.3 months) for Bosulif1. With a longer duration of exposure, the safety and tolerability profile remains consistent with the primary analysis of the ASCEMBL trial1-4. The most common (incidence ≥ 20%) adverse reactions reported in this analysis were thrombocytopenia (29.5%) and neutropenia (23.1%) in the Scemblix arm; and diarrhea (71.1%), nausea (46.1%), increased ALT (28.9%), vomiting (26.3%), rash (23.7%), increased AST (21.1%) and neutropenia (21.1%) in the Bosulif arm1.

"We are excited to see the continued benefit with Scemblix for this long-underserved patient population," said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development at Novartis. "These data are encouraging as we continue to challenge the current standard of care in CML by exploring if and how Scemblix can help more patients living with this disease."

Scemblix received FDA approval in October 2021 and is currently available for physicians to prescribe to appropriate patients in the US2. Scemblix is also being evaluated in studies across multiple treatment lines and indications for CML-CP, including the ASC4FIRST Phase III study for newly diagnosed adult patients, as well as in a Phase Ib/II dose assessment study in pediatric patients with Ph+ CML-CP. Trial-in-progress posters for both are being presented at ASH (Free ASH Whitepaper)13-22.

To learn more about our long-standing commitment to transforming the lives of patients with CML with bold science, the latest information from Novartis and access to our ASH (Free ASH Whitepaper) 2021 scientific presentations, visit the Novartis Oncology Congress Hub at View Source

About Scemblix (asciminib)
Scemblix (asciminib) is indicated for the treatment of adult patients with Ph+ CML-CP pre-treated with two or more TKIs, as well as adult patients with Ph+ CML-CP with the T315I mutation. The first indication is approved under the US FDA Accelerated Approval Program based on MMR rate at 24 weeks; continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence2.

Scemblix is the first FDA-approved CML treatment that binds to the ABL myristoyl pocket2. This novel mechanism of action, also known in scientific literature as a STAMP inhibitor, can help address resistance in patients with CML previously treated with two or more TKIs and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells3-12.

Novartis has initiated regulatory filings for Scemblix in multiple countries and regions across the globe.

Scemblix represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for CML-CP3-20. Specifically, the ASC4FIRST Phase III study (NCT04971226) evaluates Scemblix as a first-line treatment and is in the recruitment phase14,21.

About Novartis Commitment to CML
Novartis has a long-standing scientific commitment to patients living with CML. For more than 20 years, our bold science has helped transform CML into a chronic disease for many patients. Despite these advancements, we’re not standing still. We continue to research ways to target the disease, seeking to address the challenges with treatment resistance and/or intolerance that many patients face. Novartis also continues to reimagine CML care through its commitment to sustainable access for patients and collaboration with the global CML community.

Indication
SCEMBLIX (asciminib) tablets is a prescription medicine used to treat adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitor (TKI) medicines. The effectiveness of SCEMBLIX in these patients is based on a study that measured major molecular response (MMR) rates. No clinical information is available to show if these patients treated with SCEMBLIX live longer or if their symptoms improve. Ongoing studies exist to find out how SCEMBLIX works over a longer period of time.

SCEMBLIX is also approved for use in adults with Ph+ CML in CP with the T315I mutation.

It is not known if SCEMBLIX is safe and effective in children.

Important Safety Information
SCEMBLIX (asciminib) tablets may cause low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and low red blood cell counts (anemia). Patients should tell their doctor right away if they have unexpected bleeding or easy bruising; blood in their urine or stools; fever; or any signs of an infection. SCEMBLIX may increase enzymes in the patient’s blood called amylase and lipase, which may be a sign of inflammation of the pancreas (pancreatitis). Patients should tell their doctor right away if they have sudden stomach-area pain or discomfort, nausea, or vomiting. During treatment with SCEMBLIX, doctors may check their patients’ blood pressure and treat any high blood pressure as needed. Patients should tell their doctor if they develop elevated blood pressure or symptoms of high blood pressure including confusion, headaches, dizziness, chest pain, or shortness of breath.

If a patient has an allergic reaction while on SCEMBLIX, they should stop taking SCEMBLIX and get medical help right away. Signs or symptoms of an allergic reaction include trouble breathing or swallowing; feeling dizzy or faint; swelling of the face, lips, or tongue; fever; skin rash or flushing; or a fast heartbeat. SCEMBLIX may cause heart and blood vessel problems, including heart attack; stroke; blood clots or blockage of patient’s arteries; heart failure; and abnormal heartbeat which can be serious and may sometimes lead to death. These heart and blood vessel problems can happen in people with risk factors or a history of these problems and/or previously treated with multiple TKI medicines. Patients should tell their doctor right away if they get shortness of breath; chest pain or pressure; a feeling like their heart is beating too fast or they feel abnormal heartbeats; swelling in their ankles or feet; dizziness; weight gain; numbness or weakness on one side of their body; decreased vision or loss of vision; trouble talking; pain in their arms, legs, back, neck, or jaw; headache; or severe stomach-area pain.

Before taking SCEMBLIX, patients should tell their doctor about all of their medical conditions, including if they have a history of pancreatitis; a history of heart problems; or blood clots in their arteries and veins (types of blood vessels). SCEMBLIX can harm an unborn baby. Women should tell their doctor right away if they become pregnant or think they may be pregnant during treatment with SCEMBLIX. Women who are able to become pregnant should have a pregnancy test before they start SCEMBLIX and should use effective birth control during treatment and for 1 week after the last dose of SCEMBLIX. Women should not breastfeed during treatment and for 1 week after their last dose of SCEMBLIX.

Patients should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. SCEMBLIX and other medicines may affect each other, causing side effects. The most common side effects of SCEMBLIX include nose, throat, or sinus (upper respiratory tract) infections; muscle, bone, or joint pain; rash; tiredness; nausea; and diarrhea. The most common blood test abnormalities include decreased blood counts of platelets, white blood cells, and red blood cells; and increased blood levels of triglycerides, creatine kinase, liver enzymes, or pancreas enzymes (amylase and lipase).

Please see full Prescribing Information for SCEMBLIX, available at View Source

On December 11, 2021 Novartis reported that Kymriah (tisagenlecleucel) demonstrated strong efficacy in high-risk patients with relapsed or refractory (r/r) follicular lymphoma (FL) based on a subgroup analysis from an approximately 17-month median follow-up of the pivotal Phase II ELARA study1 (Press release, Novartis, DEC 11, 2021, View Source [SID1234596842]). These results were presented in an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) (Abstract #131).

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In the subgroup analysis, results showed high rates of durable responses were induced by Kymriah in patients for the majority of high-risk disease subgroups, who typically have a poor prognosis. Complete response rate (CRR), overall response rate (ORR), and durability of response (DOR) were maintained in most patients in the high-risk subgroups, with the exception of those in three of the nine subgroups analyzed: those with progression-of-disease within two years (POD24), high total metabolic tumor volume (TMTV) and patients who had received five or more prior lines of therapy1.

"It’s truly exciting to see that after treatment with Kymriah in patients with difficult-to-treat, high-risk follicular lymphoma, patients are experiencing long-lasting responses with a low risk of severe adverse events," said Catherine Thieblemont, MD, PhD, Professor of Hematology in the Paris VII- University, France and Head of the Hemato-Oncology Unit of St-Louis Hospital in Paris.

High and durable responses were seen in the overall population of the ELARA study in which 94 patients were evaluable for efficacy with a median follow-up of approximately 17 months. The CRR was 69% (95% CI, 60-78), ORR was 86% (95% CI, 78-92), 12-month progression-free survival (PFS) was 67% (95% CI, 56-76) and nine-month DOR was 76% (95% CI, 65-84). For patients who had a complete response (CR), 12-month PFS was 86% (95% CI, 74-92) and the estimated DOR rate was 87% (95% CI, 75-93). In the safety analysis (n=97), the safety profile of Kymriah continued to reflect the remarkable results seen in earlier ELARA analyses. Within eight weeks of infusion, 48% of patients experienced cytokine release syndrome (CRS), with no patients experiencing CRS of grade 3 or higher as defined by the Lee scale, 37% had neurological events (3% were greater than or equal to grade 3) and there were no treatment-related deaths1.

A separate analysis of hospitalization and intensive care unit patterns for patients treated in the inpatient and outpatient settings in the ELARA trial suggest Kymriah may reduce healthcare resource utilization for patients with r/r FL treated in the outpatient setting (Abstract #3533). Among patients treated in the outpatient setting (n=17), 35% did not require hospitalization during the first two months of the post-infusion period; those who did had a lower median average length of stay than the patients infused in an inpatient setting (4 days [n=17] vs 12 days [n=80]). Additionally, the mean hospitalization costs in the post-infusion period were substantially lower in the outpatient versus inpatient setting2.

"The ability to administer Kymriah, a potentially definitive treatment, in the outpatient setting may reduce the burden of therapy for patients and their care teams," said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis. "The breadth of follicular lymphoma data presented at this year’s ASH (Free ASH Whitepaper) demonstrate the potential for Kymriah to provide transformative results and a positive impact on health systems overall."

Novartis is committed to bringing the benefits of Kymriah to more patients with advanced blood cancers worldwide, with regulatory submissions for follicular lymphoma in the US and EU complete in October 2021. If approved in this indication, Novartis will look to confirm these results of the ELARA trial and related analyses in the real-world setting.

About follicular lymphoma
Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma (NHL), is an indolent lymphoma, and represents approximately 22% of NHL cases3,4. It is often an unrelenting malignancy with a relapsing and remitting pattern5,6. Throughout the lifetime of a patient with relapsing FL, he or she may be exposed to a median of five lines of prior treatment, with an upper range of 13 lines7,8. Although patients in third or later line treatment for FL have multiple systemic therapies available, the efficacy of these regimens drops off rapidly in later lines5. Additionally, because of this relapsing and remitting pattern, patients who are refractory to treatment or relapse may exhaust available treatment options5.

About the ELARA trial
ELARA is a Phase II, single-arm, multicenter, open-label trial investigating the efficacy and safety of Kymriah in adult patients with r/r FL after at least two prior therapies. This international trial has enrolled patients from over 30 sites in 12 countries worldwide. The primary endpoint is complete response rate (CRR) based on best response by central review (Lugano 2014 criteria). Patients evaluable for efficacy had measurable disease at infusion and more than six months of follow-up from infusion or discontinued early. After infusion, disease assessments were performed every three months. In a high-risk subgroup analysis, patients evaluated included those with prior hematopoietic stem cell transplant, double-refractory disease, high Follicular Lymphoma International Prognostic Index at study entry, high lactate dehydrogenase at baseline, high C-reactive protein prior to infusion, radiological bulky disease, progression-of-disease within two years (POD24), high total metabolic tumor volume (TMTV), and patients who had received five or more prior lines of therapy1. Secondary endpoints include overall response rate, duration of response, progression-free survival, overall survival and safety. Primary analysis data announced at ASCO (Free ASCO Whitepaper) 2021 showed Kymriah led to responses for the majority of patients treated, with 66% achieving a complete response (95% CI, 56-75). The overall response rate was 86% (95% CI, 78-92)9. Importantly, no patients in ELARA trial experienced grade 3 or higher cytokine release syndrome related to Kymriah within the first 8 weeks following infusion, the most common side effect associated with CAR-T therapy9.

About Novartis commitment to Oncology Cell Therapy
Novartis has a mission to reimagine medicine by bringing curative cell therapies to patients worldwide. Novartis has a deep CAR-T pipeline and ongoing investment in manufacturing and supply chain process improvements. With active research underway to broaden the impact of cell and gene therapy in oncology, Novartis is going deeper in hematological malignancies, reaching patients with other cancer types and evaluating next-generation CAR-T cell therapies that focus on new targets and utilize new technologies.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, is the foundation of Novartis’ commitment to CAR-T cell therapy.

Kymriah is currently approved for use in at least one indication in 30 countries and at more than 350 certified treatment centers, with the ambition for further expansion to help fulfill the ultimate goal of bringing CAR-T cell therapy to every patient in need.

Novartis has a global CAR-T manufacturing footprint that includes both Novartis-owned and contract manufacturing sites. This comprehensive, integrated footprint strengthens the flexibility, resilience and sustainability of the Novartis manufacturing and supply chain.

US FDA approved indications for Kymriah
Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T cell immunotherapy, which is indicated for:

The treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
The treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma (FL). Limitations of Use: Kymriah is not indicated for treatment of patients with primary central nervous system lymphoma.
Kymriah (tisagenlecleucel) US Important Safety Information
KYMRIAH may cause side effects that are severe or life-threatening, such as Cytokine Release Syndrome (CRS) or neurological toxicities. Patients with CRS may experience symptoms including difficulty breathing, fever (100.4◦F/38◦C or higher), chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their healthcare provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, KYMRIAH is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYMRIAH REMS.

Serious allergic reactions, including anaphylaxis, may occur after KYMRIAH infusion. KYMRIAH can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their healthcare provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient’s healthcare provider will do blood tests to check all their blood cell counts after treatment with KYMRIAH. Patients should be advised to tell their healthcare provider right away if they get a fever, are feeling tired, weak, or short of breath, or have bruising or bleeding.

Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with KYMRIAH and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with KYMRIAH. Patients should tell their healthcare provider about their treatment with KYMRIAH before receiving a live vaccine.

After treatment with KYMRIAH, patients will be monitored lifelong by their healthcare provider, as they may develop secondary cancers or recurrence of their cancer.

Patients should not drive, operate heavy machinery, or do other dangerous activities for eight weeks after receiving KYMRIAH because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness, and seizures.

Some of the most common side effects of KYMRIAH are difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, dizziness/lightheadedness, and headache. However, these are not all the possible side effects of KYMRIAH. Patients should talk to their healthcare provider for medical advice about side effects.

Prior to a female patient starting treatment with KYMRIAH, their healthcare provider may do a pregnancy test. No information is available for KYMRIAH use in pregnant or breast-feeding women. Therefore, KYMRIAH is not recommended for women who are pregnant or breast feeding. Patients should talk to their healthcare provider about birth control and pregnancy.

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

After receiving KYMRIAH, patients should be advised that some commercial HIV tests may cause a false-positive test result. Patients should also be advised not to donate blood, organs, tissues, sperm, oocytes, and other cells after receiving KYMRIAH.