On December 7, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported new data on two investigational CD20-CD3 T-cell engaging bispecific antibodies, mosunetuzumab and CD20-TCB, in people with relapsed or refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL) (Press release, Genentech, DEC 7, 2019, View Source [SID1234552054]). Results from the Phase I/Ib GO29781 study of mosunetuzumab, including data from people previously treated with chimeric antigen receptor (CAR) T-cell therapy, will be presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting during the Plenary Scientific Session. The Plenary Scientific Session highlights the top six abstracts submitted to the meeting, as determined by the ASH (Free ASH Whitepaper) Program Committee. Additionally, results from the Phase I/Ib NP30179 study evaluating CD20-TCB as a combination therapy with Gazyva (obinutuzumab) for people with R/R NHL, will be presented.

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"We’re encouraged by these early results, which suggest that our novel bispecific cancer immunotherapies may help people with relapsed or treatment-refractory disease who need more options."

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"Despite recent treatment advancements, slow-growing and aggressive non-Hodgkin’s lymphomas present increasingly difficult management challenges with each subsequent relapse," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "We’re encouraged by these early results, which suggest that our novel bispecific cancer immunotherapies may help people with relapsed or treatment-refractory disease who need more options."

The GO29781 study evaluated mosunetuzumab in patients with R/R NHL, including patients who have relapsed following, or are resistant to, CAR T-cell therapy – a patient population with limited treatment options. Results from this dose-escalation study showed encouraging efficacy with an objective response rate (ORR) of 62.7 percent (n=42/67) in slow-growing NHL and 37.1 percent (n=46/124) in aggressive NHL. Additionally, data demonstrated a complete response (CR) rate of 43.3 percent (n=29/67) in slow-growing NHL and 19.4 percent (n=24/124) in aggressive NHL. CRs showed durability, with 82.8 percent (n=24/29) of patients with slow-growing NHL remaining in remission up to 26 months off initial treatment and 70.8 percent (n=17/24) of patients with aggressive NHL, remaining in remission up to 16 months off initial treatment. Of the participants who received prior CAR T-cell therapy, the ORR was 38.9 percent (n=7/18), and 22.2 percent (n=4/18) achieved a CR. Adverse reactions included cytokine release syndrome (CRS) in 28.9 percent of patients with 20.0 percent at Grade 1 and 1.1 percent at Grade 3. Grade 3 neurological adverse events occurred in 3.7 percent of patients.

Results from the Phase I/Ib dose-escalation NP30179 study, evaluating CD20-TCB at doses ranging from 0.6 mg to 16 mg plus Gazyva in people with R/R B-cell NHL, showed an ORR of 54 percent (n=15/28) and a CR rate of 46 percent (n=13/28). This included an ORR and CR of 66.7 percent (n=4/6) in people with follicular lymphoma and an ORR of 50.0 percent (n=11/22) and a CR of 40.9 percent (n=9/22) in aggressive NHL. The most frequently observed adverse event across all treatment doses was CRS, occurring in 67.9 percent of patients (n=19/28), with the majority of events being low grade (Grade 1-2).

Both mosunetuzumab and CD20-TCB continue to be evaluated in a robust clinical development program, investigating the treatments as monotherapies and in combination with other therapies, in people with slow-growing and aggressive forms of NHL.

About Genentech’s Investigational Bispecifics

Genentech is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and CD20-TCB, 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 CD20-TCB 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. The clinical development programs for mosunetuzumab and CD20-TCB 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 and follicular lymphoma.

About the GO29781 study

The GO29781 study [NCT02500407] is a Phase I/Ib, 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 best objective response rate by revised International Working Group criteria, maximum tolerated dose, and tolerability.

About the NP30179 study

The NP30179 study [NCT03075696] is a Phase I/Ib, multicenter, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of CD20-TCB. In this study, CD20-TCB is assessed as a single agent and in combination with Gazyva, following pre-treatment with a one-time, fixed dose of Gazyva, in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose, and tolerability.

About Non-Hodgkin’s Lymphoma

There are two main types of lymphoma: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL). NHL has two subsets, aggressive and indolent (slow-growing).

NHL represents approximately 85 percent of all lymphomas diagnosed. According to the American Cancer Society, it is expected that nearly 74,000 people will be diagnosed with NHL in the United States in 2019, and nearly 20,000 will die from the disease.

Most cases of NHL start in B-lymphocytes, cells that are part of the body’s immune system and help to defend the body against infections. B-cell lymphoma develops when these cells become cancerous and begin to multiply and collect in the lymph nodes or lymphatic tissues such as the spleen.

Gazyva Indications

Gazyva (obinutuzumab) is a prescription medicine used:

With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
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.
With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.
Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect 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 the 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, their 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. The patient’s weakened immune system 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 tell their healthcare provider 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 doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. 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 infusion reaction 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 infusion reactions 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 of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81 percent), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within 6 months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent).The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.

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, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor 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. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.
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 7, 2019 ALX Oncology, a clinical-stage immuno-oncology company developing therapies to block the CD47 checkpoint mechanism, reported new results from the hematological portion of the ALX148 Phase 1 program at the 2019 ASH (Free ASH Whitepaper) Annual Meeting [publication number #1953] (Press release, ALX Oncology, DEC 7, 2019, View Source [SID1234552053]). As of November 01, 2019, twenty-nine patients with relapsed or refractory non-Hodgkin lymphoma (NHL) were administered ALX148 in combination with a standard rituximab regimen. Objective responses were observed at all dose levels administered.

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Key results:

ALX148 was well tolerated with no dose limiting toxicities, and no maximum tolerated dose reached with a maximum administered dose of 15 mg/kg once weekly (molar equivalent to 30 mg/kg once weekly of an antibody). The most common treatment-related adverse event was Grade 1/2 rash.
Response-evaluable patients with relapsed/refractory NHL (n=21) who were administered ALX148 (10 mg/kg once weekly) demonstrated an objective response rate (ORR) of 43% and median progression free survival (mPFS) of 7.3 months.
In patients with aggressive NHL (n=14) an ORR of 36% and mPFS of 3.1 months were observed.
In patients with indolent NHL (n=7) an ORR of 57% was observed and mPFS was not reached.
Two patients achieved complete response, one of whom was refractory to prior rituximab therapy.
In patients with rituximab refractory disease (n=9) an ORR of 44% was observed.
In initial response-evaluable patients with relapsed/refractory NHL (n=3) administered ALX148 (15 mg/kg once weekly) an ORR of 67% was reported, and mPFS was not reached.
ALX148 demonstrates antibody-like and linear pharmacokinetics at the two dose levels evaluated with complete CD47 target occupancy in combination with rituximab.
"The compelling anti-tumor activity seen in relapsed and refractory patients with non-Hodgkin lymphoma confirms the central role of the CD47/SIRPa myeloid checkpoint as a critical target in maximizing tumor control," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "ALX148, a myeloid checkpoint inhibitor, has previously demonstrated emerging activity in head and neck squamous cell carcinoma, gastric and gastroesophageal junction cancer, and now, additionally, in non-Hodgkin lymphoma. The safety profile of ALX148 observed across the clinical program differentiates from all other CD47 targeted agents currently in the clinic, enabling broad development of ALX148 in multiple cancer indications. We believe ALX148 has the potential to become a cornerstone of treatment for patients with cancer.

Conference Call on December 12th at 8:00 a.m. EST
ALX Oncology will host a conference call on Thursday, December 12, 2019 at 8:00 a.m. EST to discuss the Company’s lead development candidate, ALX148, a next generation CD47 myeloid checkpoint inhibitor and its clinical data in hematologic and solid cancers. In addition to ALX Oncology’s executive management team, three distinguished physicians will be featured on the call:

Justin Gainor, MD – Director of Targeted Immunotherapy, Henri and Belinda Termeer Center for Targeted Therapies, Center for Thoracic Cancers, Assistant Professor of Medicine, Harvard Medical School in Boston, Massachusetts on ALX148 in patients with head and neck squamous cell carcinoma
Tae Min Kim, MD, PhD – Professor, Department of Internal Medicine, Division of Hematology and Medical Oncology at Seoul National University Hospital in Seoul, South Korea on ALX148 in patients with non-Hodgkin lymphoma
Jeeyun Lee, MD – Associate Professor of Hematology/Oncology at the Samsung Medical Center, Sungkyunkwan University School of Medicine in Seoul, South Korea on ALX148 in patients with gastric and gastroesophageal junction cancer
To access the conference call, please dial (844) 467-7655 or (409) 983-9840 (international) at least 10 minutes prior to the start time and refer to conference ID 9162888. Presentation slides will be available to download from the Company’s website www.alxoncology.com.

On December 7, 2019 Kite, a Gilead Company (Nasdaq: GILD), reported new data from the ZUMA-1 trial of Yescarta (axicabtagene ciloleucel) in adult patients with refractory large B-cell lymphoma (Press release, Kite Pharma, DEC 7, 2019, View Source [SID1234552051]). These results included updated overall survival data from the pivotal phase 2 study after three years following a single infusion of Yescarta, as well as an analysis from a separate safety management cohort of patients receiving early steroid intervention for cytokine release syndrome (CRS) and neurologic events. The data were presented today at the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, in Orlando from December 7–10, 2019.

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With a minimum follow-up of three years after a single infusion of Yescarta (median follow-up of 39.1 months), approximately half (n=47/101; 47 percent) of patients with refractory large B-cell lymphoma in ZUMA-1 pivotal phase 2 cohorts were alive, and the median overall survival (OS) was 25.8 months. These updated three-year survival data were presented as part of a ZUMA-1 analysis evaluating mechanism of secondary treatment failure following treatment with Yescarta (Abstract #203).

"With approximately half of patients with refractory large B-cell lymphoma in our registrational trial alive three years following treatment with Yescarta, we are delivering towards our goal of potentially life-saving therapy for many patients who previously faced limited treatment options and a poor prognosis prior to the introduction of CAR T therapy," said Christi Shaw, Chief Executive Officer of Kite. "These results, coupled with an analysis that suggests a reduced risk of severe CRS and neurological events with earlier use of steroids, further support our ongoing leadership in cell therapy and commitment to patient care."

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

Updated results from a separate ZUMA-1 safety management study (Cohort 4) were also presented at the meeting (Abstract #243). In this analysis, patients with relapsed or refractory large B-cell lymphoma treated with Yescarta received earlier steroid intervention, beginning when patients experienced Grade 1 neurologic events or experienced Grade 1 CRS with no improvement after three days of supportive care. Patients could receive optional bridging chemotherapy prior to Yescarta infusion.

In the analysis, 41 patients had received Yescarta, with a median follow-up of 8.7 months; 73 percent of patients received corticosteroids and 76 percent received tocilizumab. Earlier steroid use appeared to decrease the percentage of patients with Grade ≥3 CRS (2 percent) and neurologic events (17 percent), each of which were numerically lower than rates in the registrational cohorts of ZUMA-1 (13 percent CRS, 31 percent neurologic events). There were no Grade 4 or 5 CRS or neurologic events and no Grade 5 AEs related to Yescarta in Cohort 4.

Objective response rate per investigator assessment was 73 percent in Cohort 4, with 51 percent of patients achieving a complete response. The median duration of response was 8.9 months. Fifty-four percent of patients in this cohort remained in an ongoing response with at least six months of follow-up after Yescarta infusion. Median OS in Cohort 4 has not been reached.

"Results from ZUMA-1 Cohort 4 demonstrate that early steroid intervention has the potential to reduce the rate of severe CRS and neurologic events while appearing to maintain comparably impressive efficacy for Yescarta to the pivotal ZUMA-1 study cohorts," said Max S. Topp, MD, ZUMA-1 Cohort 4 investigator and Professor and Head of Hematology, University Hospital of Wuerzburg, Germany. "Data from this cohort suggest this approach with earlier steroid use may further improve the benefit/risk profile of this CAR T therapy."

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

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

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

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

HYPERSENSITIVITY REACTIONS: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

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

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

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

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

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

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

On December 7, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported updated and long-term follow-up analyses from two clinical trials evaluating ADCETRIS (brentuximab vedotin) and OPDIVO (nivolumab) in frontline Hodgkin lymphoma (HL) patients aged 60 years and older and in relapsed or refractory classical HL (Press release, Seattle Genetics, DEC 7, 2019, View Source [SID1234552050]). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. ADCETRIS and OPDIVO are not approved in combination for the treatment of HL. Results were presented today at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 7-10 in Orlando, Fla.

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"We continue to evaluate ADCETRIS in combination with novel therapies, such as checkpoint inhibitors, with the goal of identifying new options for CD30-expressing lymphomas where there is high unmet need," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "These data presentations at ASH (Free ASH Whitepaper) reinforce our strong commitment to the ADCETRIS clinical development program, potentially moving into new patient populations and novel combination treatment strategies."

Phase 2 Study of Frontline Brentuximab Vedotin Plus Nivolumab in Patients with Hodgkin Lymphoma Aged ≥ 60 Years (Abstract #237, oral presentation at 2:30 p.m. ET on Saturday, December 7, 2019)
Data were presented from an updated analysis from the phase 2 clinical trial evaluating ADCETRIS in combination with OPDIVO as frontline therapy for HL patients aged 60 years and older. Data were reported from 21 patients, and the median age was 72 years. The majority of patients (76 percent) had stage III/IV disease at the time of diagnosis. These results will be highlighted in an oral presentation by Christopher A. Yasenchak, M.D., Willamette Valley Cancer Institute and Research Center/US Oncology Research, Ore., and include:

Of 19 response-evaluable patients, 18 patients (95 percent) had an objective response, including 13 patients (68 percent) with a complete response and five patients (26 percent) with a partial response. All response-evaluable patients experienced tumor reduction (complete response + partial response + stable disease) following treatment with ADCETRIS in combination with OPDIVO. Median duration of response was not yet reached and the maximum duration of response was 22 months and ongoing (95% CI: 7.06, -).
The most common treatment-related adverse events of any grade occurring in at least 20 percent of patients were fatigue, diarrhea, pyrexia, infusion related reaction, peripheral motor neuropathy, peripheral sensory neuropathy and increase in lipase. One treatment-related serious adverse event was pyrexia. Fifty-seven percent of patients (12/21) had at least one treatment-related adverse event greater than or equal to Grade 3, most commonly increase in lipase (24 percent, 5/21), peripheral motor neuropathy and peripheral sensory neuropathy (each 14 percent, 3/21), and fatigue and hyponatremia (each 10 percent, 2/21).
Two-Year Follow-up Results from the Phase 1-2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (Abstract #238, oral presentation at 2:45 p.m. ET on Saturday, December 7, 2019)
Data were reported from 93 patients with relapsed or refractory classical HL after failure of frontline therapy who received the combination regimen of ADCETRIS plus OPDIVO. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 34 years. These results will be highlighted in an oral presentation by Alison J. Moskowitz, M.D., Memorial Sloan Kettering Cancer Center, NY, and include:

Of the 91 treated patients, 85 percent (77/91) had an objective response, including 67 percent (61/91) with a complete response, 16 patients with a partial response and six patients had stable disease.
Of the 91 treated patients, 67 patients received an ASCT per trial protocol with no additional salvage therapy.
For all treated patients, the two-year progression-free survival (PFS) was 79 percent (95% CI: 68%, 87%). For the 67 patients who received an ASCT per trial protocol, the two-year PFS was 92 percent (95% CI: 80%, 97%). Median follow-up for all treated patients was 24.2 months (range 1.8-41.7) and the median PFS was not reached. Estimated overall survival at two years was 94 percent (95% CI: 85%, 97%) and median overall survival was not yet reached.
Peripheral immune signatures were consistent with an activated T-cell response.
Prior to ASCT, the most common adverse events of any grade occurring in more than 20 percent of patients were nausea, infusion related reaction, fatigue, diarrhea, pruritus, headache, vomiting and pyrexia. Other adverse events included peripheral neuropathy in 16 patients (18 percent) and neutropenia in six patients (7 percent). Two patients (2 percent) discontinued treatment due to adverse events, Grade 3 peripheral neuropathy and increased gamma-glutamyltransferase. Serious adverse events occurred in 14 patients (15 percent), including pneumonia, pneumonitis and pyrexia (two patients each); and Grade 3 Guillain-Barre syndrome (one patient).
About Classical Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Classical Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

According to the American Cancer Society, approximately 8,110 cases of Hodgkin lymphoma will be diagnosed in the United States during 2019 and 1,000 will die from the disease. Approximately half of all newly diagnosed Hodgkin lymphoma patients have Stage III/IV disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three completed phase 3 trials: ECHELON-2 trial in frontline peripheral T-cell lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine and dacarbazine).

ADCETRIS has received marketing authorization by regulatory authorities in 73 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

On December 7, 2019 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported the receipt of a development milestone payment from Janssen and the presentation of updated data from the Phase 1 dose escalation trial of cusatuzumab in combination with azacytidine for the treatment of newly diagnosed acute myeloid leukemia (AML) at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, argenx, DEC 7, 2019, View Source [SID1234552049]).

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argenx will receive the first development milestone payment of $25 million from its global collaboration and license agreement with Cilag GmbH International, an affiliate of the Janssen Pharmaceutical Companies of Johnson & Johnson. The milestone payment was triggered by the achievement of a prespecified enrollment threshold in the first trial to start under the collaboration. This dose-confirming Phase 2 pivotal CULMINATE trial of cusatuzumab is being conducted in combination with azacytidine for the treatment of newly diagnosed elderly patients with AML who are unfit for intensive chemotherapy.

"This milestone payment marks the progress made across our global collaboration with Janssen. Two trials are now underway in newly diagnosed populations with more trials expected to intiate next year in different AML settings and subpopulations. We continue to believe in the potential of the CD70/CD27 axis as a novel approach within the AML treatment landscape. The data update today further support the use of cusatuzumab in combination to treat this vulnerable patient population," commented Tim Van Hauwermeiren, Chief Executive Officer of argenx.

Key Highlights from ASH (Free ASH Whitepaper)

Adrian Ochsenbein, M.D. from the University of Bern presented translational data in support of the dual modes of action of cusatuzumab, including the blocking of CD70/CD27 signaling to stop proliferation of leukemic stem cells and cell killing via Fc-dependent, complement-dependent cytotoxicity and enhanced antibody-dependent cellular cytotoxicity (ADCC) via POTELLIGENT technology. Dr. Ochsenbein also showed updated data as of the new cut-off date of February 2019 from the Phase 1 dose escalation trial of cusatuzumab in combination with azacytidine in 12 newly diagnosed elderly patients with AML who are unfit for intensive chemotherapy.

100% of patients achieved a response including eight with a complete response (CR), two with a complete response with incomplete hematologic recovery (CRi), and two with a partial response (PR); 83% of patients achieved either a CR or CRi

Of the nine CR/CRi patients evaluable for minimal residual disease (MRD) negativity, four achieved MRD negativity using a threshold of 10-3 which is consistent with the previous data cut-off in October 2018

Four patients have remained in the study for at least 12 months

Three patients from the study have been re-classified with risk category based on new mutation information or a reassessment of existing mutation information

Cusatuzumab continued to be well-tolerated in patients with AML across the different doses

In addition to the CULMINATE trial in the newly diagnosed unfit AML population, cusatuzumab is also being evaluated in a Phase 1b platform study to explore combinations with standard AML therapies with the first trial exploring combinations of venetoclax, cusatuzumab and azacytidine.