On December 5, 2020 Kite, a Gilead Company (Nasdaq: GILD), reported follow-up results from the pivotal ZUMA-2 trial of Tecartus (brexucabtagene autoleucel, formerly KTE-X19) in adult patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, Kite Pharma, DEC 5, 2020, View Source [SID1234572233]). At a median follow-up of 17.5 months (n=60 evaluable for efficacy), 92 percent of patients had achieved a response, including 67 percent with a complete response (CR). Secondary endpoints of median duration of response, progression-free survival (PFS) and overall survival (OS) all were not yet reached. These data were presented at the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #1120).

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"Patients with mantle cell lymphoma face a disease that often becomes more aggressive over time and nearly always relapses after initial therapy," said Michael Wang, MD, Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "Many patients with relapsed or refractory MCL will have high-risk disease that is more likely to keep progressing after treatment, so our goal with any therapy is to provide durable remission. With more than half of the patients in the ZUMA-2 trial still alive at nearly one and a half years after infusion, these results reinforce brexucabtagene autoleucel’s potential to address the gap in existing treatment."

Among all efficacy-evaluable patients (n=60), 48 percent had ongoing responses at data cut-off. Estimates for PFS and OS at 15 months were 59 percent and 76 percent, respectively. The first 28 patients treated had a median follow-up of 32.3 months, and 39 percent of these patients remain in remission with no further therapy.

Among all patients (n=68), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events (NE) occurred in 15 percent and 31 percent of patients, respectively. No new Grade 5 events occurred with additional follow-up.

"These Tecartus data build on the significant response rates seen previously with an impressive durability, which continues to show that we have a potentially transformative treatment option for patients with relapsed or refractory MCL," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "As we continue to observe longer-term results with Tecartus, as well as with the most recent four-year results for Yescarta, our first CAR T-cell therapy, we are encouraged by the unparalleled long-term survival benefits that may be possible with these cell therapies."

In July, Tecartus became the first CAR T-cell therapy to receive accelerated approval from the FDA for the treatment of relapsed or refractory mantle cell lymphoma, based on overall response rate and durability of response. Continued approval for this indication may be contingent upon additional data from a confirmatory trial. The Tecartus U.S. Prescribing Information has a Boxed Warning in its product label regarding the risks of CRS and neurologic toxicities, and Tecartus is approved with a risk evaluation and mitigation strategy (REMS) due to these risks; see below for Indication and Important Safety Information.

About Mantle Cell Lymphoma

MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the "mantle zone" of the lymph node and predominantly affects men over the age of 60. MCL is highly aggressive following relapse, with many patients progressing following therapy.

About ZUMA-2

ZUMA-2 is an ongoing, single arm, open-label trial that enrolled 74 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint is objective response rate (ORR) per the Lugano Classification (2014), defined as the combined rate of CR and partial responses as assessed by an Independent Radiologic Review Committee (IRRC).

About Tecartus

Tecartus is an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP manufacturing process that includes T cell enrichment, a necessary step in certain B-cell malignancies in which circulating lymphoblasts are a common feature. In addition to MCL, Tecartus is also currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.

Tecartus Indication

Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed.
Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred following treatment with Tecartus. In ZUMA-2, CRS occurred in 91% (75/82) of patients receiving Tecartus, including ≥ Grade 3 CRS in 18% of patients. Among the patients who died after receiving Tecartus, one had a fatal CRS event. The median time to onset of CRS was three days (range: 1 to 13 days) and the median duration of CRS was ten days (range: 1 to 50 days). Among patients with CRS, key manifestations (>10%) included fever (99%), hypotension (60%), hypoxia (37%), chills (33%), tachycardia (37%), headache (24%), fatigue (19%), nausea (13%), alanine aminotransferase increased (13%), aspartate aminotransferase increased (12%), and diarrhea (11%). Serious events associated with CRS included hypotension, fever, hypoxia, acute kidney injury, and tachycardia.

Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

Neurologic Toxicities, including those that were life-threatening, occurred following treatment with Tecartus. In ZUMA-2, neurologic events occurred in 81% of patients, 37% of whom experienced Grade ≥3 adverse reactions. The median time to onset for neurologic events was six days (range: 1 to 32 days). Neurologic events resolved for 52 out of 66 (79%) patients with a median duration of 21 days (range: 2 to 454 days). Three patients had ongoing neurologic events at the time of death, including one patient with serious encephalopathy. The remaining unresolved neurologic events were either Grade 1 or Grade 2. Fifty-four (66%) patients experienced CRS by the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. 85% of all treated patients experienced the first CRS or neurological event within the first seven days after Tecartus infusion.

The most common neurologic events (>10%) included encephalopathy (51%), headache (35%), tremor (38%), aphasia (23%), and delirium (16%). Serious events including encephalopathy, aphasia, and seizures occurred.

Monitor patients daily for at least seven days at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly.

REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that:

Healthcare facilities that dispense and administer Tecartus 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 two doses of tocilizumab are available for each patient for infusion within two hours after Tecartus infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Tecartus are trained in the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus.

Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. In ZUMA-2, infections (all grades) occurred in 56% of patients. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 6% of patients after Tecartus infusion 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.

Viral Reactivation

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 Tecartus infusion. In ZUMA-2, Grade ≥3 cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). Monitor blood counts after infusion.

Hypogammaglobulinemia and B-cell aplasia can occur in patients receiving treatment with Tecartus. In ZUMA-2, hypogammaglobulinemia occurred in 16% of patients. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during treatment, and until immune recovery following treatment with Tecartus.

Secondary Malignancies may develop. Monitor life-long for secondary malignancies. In the event that it 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 Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period.

Adverse Reactions: The most common adverse reactions (incidence ≥ 20%) were pyrexia, CRS, hypotension, encephalopathy, fatigue, tachycardia, arrhythmia, infection – pathogen unspecified, chills, hypoxia, cough, tremor, musculoskeletal pain, headache, nausea, edema, motor dysfunction, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia. Serious adverse reactions occurred in 66% of patients. The most common serious adverse reactions (> 2%) were encephalopathy, pyrexia, infection – pathogen unspecified, CRS, hypoxia, aphasia, renal insufficiency, pleural effusion, respiratory failure, bacterial infections, dyspnea, fatigue, arrhythmia, tachycardia, and viral infections.

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

About Yescarta

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitation of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

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

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

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

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

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

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

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

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

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

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

On December 5, 2020 Kite, a Gilead Company (Nasdaq: GILD), reported four-year follow-up data from the pivotal ZUMA-1 trial of Yescarta (axicabtagene ciloleucel) in adult patients with refractory large B-cell lymphoma (LBCL) (Press release, Kite Pharma, DEC 5, 2020, View Source [SID1234572232]). Among Yescarta-treated patients (modified intent to-treat analysis, n=101) with a minimum follow-up of four years after a single infusion of Yescarta (median follow-up of 51.1 months), the Kaplan-Meier estimate of the four-year overall survival (OS) rate was 44 percent. The data were presented today at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #1187).

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Of 111 patients enrolled in the ZUMA-1 Phase 2 cohorts, Yescarta was administered to 101 patients with refractory LBCL, and the median time from leukapheresis to complete response (CR) was less than two months. There have been no Yescarta-related secondary malignancies reported.

"With close to half of patients still alive after a single infusion of axicabtagene ciloleucel, we are transforming the way relapsed or refractory large B-cell lymphoma can be treated," said Frederick L. Locke, MD, ZUMA-1 Co-Lead Investigator and Vice Chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida. "As a practicing oncologist I continue to see these patients in the clinic, and this overall survival data confirms the durability of CAR T-cell therapy in a patient population that previously exhausted all viable treatment options."

Blood sample analyses provided by 21 patients who were treated with Yescarta and showed an ongoing response at a minimum of three years follow-up also demonstrated that 67 percent (n=14/21) had detectable CAR gene-marked cells and polyclonal B cells in blood. Additionally, normal B-cells were present in 91 percent (n=21/23) of evaluable patients. These results suggest that persistence of functional CAR T cells is not necessary for durable remissions in patients with refractory LBCL and may support long-term safety of the therapy.

"With these first-ever four-year data from a pivotal CAR T clinical trial in lymphoma, we continue to show the potential long-term survival of Yescarta in relapsed/refractory large B-cell lymphoma and push the boundaries of what is possible with this CAR T treatment," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "And equally importantly, we are encouraged by similar trends in long-term survival with real-world experience, with thousands of patients treated since Yescarta first became available."

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

Yescarta was the first 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 cytokine release syndrome (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.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

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

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

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

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

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

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

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

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

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

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

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

On December 5, 2020 GlycoMimetics’ (Nasdaq: GLYC) product candidate uproleselan — when added to a combination therapy of venetoclax and a hypomethylating agent (HMA) — was shown today in an oral presentation to break chemoresistance by dramatically and significantly reducing tumor burden as detected by circulating human AML cells after three weeks of treatment, and by significantly increasing survival (p = 0.0009) in an animal model engrafted with AML from a patient with acquired resistance to venetoclax/HMA combination therapy (Press release, GlycoMimetics, DEC 5, 2020, View Source [SID1234572223]). The oral presentation made by Dr. Kyung Hee Chang, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, at the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition supports the need for further clinical investigation to potentially extend the use of uproleselan, an investigational, first-in-class, targeted E-selectin antagonist, to other drug combinations and, in particular, to venetoclax/HMA.

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"As in previously reported models, uproleselan has shown benefit when added to multiple chemotherapy regimens. These data, showing the potential benefit of adding uproleselan to a combination therapy of venetoclax and HMA, are important given the rapid changes in the landscape of approved AML therapies as well as those in development. The data strongly support conducting a clinical trial with this combination therapy," said Rachel King, GlycoMimetics’ Chief Executive Officer.

"Given investigator interest in this data, we’re actively exploring opportunities for investigator-sponsored clinical trials to study the implications in humans. If successful, these studies would further reinforce our goal of demonstrating the value of uproleselan across the spectrum of AML patients and with a variety of therapeutic combination regimens," she added.

GlycoMimetics previously presented preclinical data showing that hypomethylating agents up-regulate the expression of E-selectin ligand on AML cells. The Company believes E-selectin upregulation increases the binding affinity of the blasts to the vascular endothelium, where E-selectin is expressed, and as a result, contributes to increased chemoresistance. By antagonizing E-selectin’s role in this cascade, GlycoMimetics believes uproleselan may be able to play a key role in deepening patient responses to or enhancing the duration of efficacy of venetoclax/HMA combinations.

Details on this presentation are as follows:

Title: Targeting E-selectin with GMI-1271 Overcomes Microenvironment-mediated Resistance to Venetoclax/HMA Therapy.
Presenters: Kyung Hee Chang, Muharrem Muftuoglu, Weiguo Zhang, Mahesh Basyal, Lauren Ostermann, William E. Fogler, John L. Magnani and Michael Andreeff.
Session: 604 Molecular Pharmacology and Drug Resistance in Myeloid Diseases.
Date and Time: Saturday, December 5, 2020. 5:00 – 8:30 p.m. ET
Presentation Time: 6:15 p.m. ET

About Uproleselan (GMI-1271)

Discovered and developed by GlycoMimetics, uproleselan is an investigational, first-in-class, targeted E-selectin antagonist. Uproleselan (yoo’ pro le’ sel an), currently in a comprehensive Phase 3 development program in AML, has received Breakthrough Therapy designation from the U.S. FDA for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. In a Phase 1/2 clinical trial, uproleselan was evaluated in both newly diagnosed elderly and relapsed or refractory patients with AML. In both populations, patients treated with uproleselan together with standard chemotherapy achieved better-than-expected remission rates and overall survival compared to historical controls, which have been derived from results from third-party clinical trials evaluating standard chemotherapy, as well as lower-than-expected induction-related mortality rates. Treatment in these patient populations was generally well-tolerated, with fewer than expected adverse effects.

On December 5, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data from the pivotal phase III MURANO and CLL14 studies support the efficacy of fixed-duration, chemotherapy-free Venclexta/Venclyxto (venetoclax)-based combinations in certain people with chronic lymphocytic leukaemia (CLL) and provide more evidence on the potential value of minimal residual disease (MRD) (Press release, Hoffmann-La Roche, DEC 5, 2020, View Source [SID1234572221]). Data were presented at the all-virtual 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Saturday 5 December 2020.

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"These results reinforce the long-term value of fixed-duration, chemotherapy-free Venclexta/Venclyxto-based combinations in CLL, potentially offering patients a significant period of time without treatment following initial therapy," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "These data also reflect our ongoing commitment to accelerating clinical advancements for patients by exploring the novel endpoint minimal residual disease as a potential predictor of patient outcomes."

Five-year data from the pivotal phase III MURANO trial continue to show sustained investigator-assessed progression-free survival (PFS) with Venclexta/Venclyxto plus MabThera/Rituxan (rituximab). Data, presented in an oral session, showed:

Venclexta/Venclyxto plus MabThera/Rituxan reduced the risk of disease progression or death by 81% (HR= 0.19; 95% CI: 0.15, 0.26; p<0.0001) compared to bendamustine plus MabThera/Rituxan (BR) in people with relapsed or refractory (R/R) CLL.
At the time of analysis, median overall survival (OS) had not been reached in either arm, however, five-year OS was 82.1% in the Venclexta/Venclyxto plus MabThera/Rituxan arm, compared to 62.2% in the BR arm (HR=0.40; 95% CI: 0.26, 0.62).
In the Venclexta/Venclyxto arm, among the 130 patients who completed two years of treatment without progressive disease, 63.8% (n=83/130) had undetectable MRD (uMRD) levels at the end of treatment. In an analysis of this patient subgroup, uMRD was associated with improved progression-free survival. Undetectable MRD, sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.
No new safety events were reported in the study.1

Data from the phase III CLL14 study contributes to growing evidence regarding the potential of MRD measurements to predict future outcomes for certain people with previously untreated CLL who were treated with fixed-duration Venclexta/Venclyxto plus Gazyva/Gazyvaro (obinutuzumab):

Patients with uMRD and a partial response (PR) had longer PFS than patients with detectable MRD and a complete response (CR).2
In collaboration with Adaptive Biotechnologies, clonal growth rate, a measure for how quickly cancer cells grow, was analysed using the next-generation sequencing Adaptive clonoSEQ Assay and insights were used to better understand the potential role of MRD in predicting outcomes. In this analysis, after treatment with fixed-duration Venclexta/Venclyxto plus Gazyva/Gazyvaro, the estimated clonal growth rate was slower and lower, suggesting more effective MRD eradication in these patients compared to those treated with Gazyva/Gazyvaro plus chlorambucil. Early data suggest a correlation between MRD responses and PFS, which will be further evaluated by the study authors.3

Exploring novel endpoints, such as MRD, is an important area of development for Roche, which continues to investigate Venclexta/Venclyxto in a robust clinical development programme. This includes the phase III CRISTALLO trial in previously untreated CLL, which uses MRD as a primary endpoint.

Venclexta/Venclyxto is approved in the US and EU in combination with MabThera/Rituxan for the treatment of adult patients with CLL who have received at least one prior therapy; in combination with Gazyva/Gazyvaro for the treatment of adult patients with previously untreated CLL; and as a monotherapy for the treatment of CLL in the presence of 17p deletion or TP53 mutation in people who are unsuitable for or have failed a B-cell receptor pathway inhibitor.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US, under the brand name Venclexta, and commercialised by AbbVie outside of the US.

*Minimal residual disease (MRD) is a measure of the number of remaining cancer cells. Undetectable MRD (uMRD), sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.

About the MURANO study 4
MURANO [NCT02005471] is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of fixed-duration Venclexta/Venclyxto (venetoclax) in combination with MabThera/Rituxan (rituximab) compared to bendamustine in combination with MabThera/Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta/Venclyxto, patients on the Venclexta/Venclyxto plus MabThera/Rituxan arm received six cycles of Venclexta/Venclyxto plus MabThera/Rituxan followed by Venclexta/Venclyxto monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukaemia, with or without 17p deletion, who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta/Venclyxto plus MabThera/Rituxan or BR. The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, overall response rate and complete response rate (with or without complete blood count recovery).

About the CLL14 study 5
CLL14 [NCT02242942] is a randomised phase III study evaluating the combination of fixed-duration Venclexta/Venclyxto (venetoclax) plus Gazyva/Gazyvaro (obinutuzumab) compared to Gazyva/Gazyvaro plus chlorambucil in adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta/Venclyxto alongside six-month duration of Gazyva/Gazyvaro (Arm A) or six-month duration of Gazyva/Gazyvaro alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyva/Gazyvaro followed by a five-week Venclexta/Venclyxto dose ramp-up to help reduce the risk of tumour burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee, minimal residual disease (MRD) status, overall response rate, complete response rate (with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. MRD-negativity, or undetectable MRD, means no cancer can be detected using a specific and highly sensitive test, and was defined as less than one cancer cell in 10,000 leukocytes. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, MD, University of Cologne.

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US, and commercialised by AbbVie, under the brand name Venclyxto outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the US Food and Drug Administration: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL and two for previously untreated acute myeloid leukaemia.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B-cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia, in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 70 countries in combination with chemotherapy for previously untreated follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world. 6 CLL mainly affects men and the median age at diagnosis is about 70 years.7 Worldwide, the incidence of all leukaemias is estimated to be over 400,000, with an incidence of over 100,000 in Europe.[8] CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.6

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting FcRH5 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On December 5, 2020 Bristol Myers Squibb (NYSE: BMY) and bluebird bio, Inc. (Nasdaq: BLUE) reported updated data evaluating the companies’ investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR) T cell therapy, idecabtagene vicleucel (ide-cel), were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, bluebird bio, DEC 5, 2020, View Source [SID1234572220]). The data include longer-term updated results from the original Phase 1 CRB-401 study of ide-cel in relapsed and refractory multiple myeloma (RRMM), including the primary endpoint of safety and exploratory endpoints of progression-free survival (PFS) and overall survival (OS). Analyses of the pivotal registrational KarMMa trial will also be presented at the ASH (Free ASH Whitepaper) meeting, including an analysis of health-related quality of life in patients with RRMM treated with ide-cel, and a subgroup analysis of outcomes for patients with high-risk RRMM. A subgroup analysis of elderly patients with RRMM treated with ide-cel in the KarMMa study were presented today. In addition, data from the ongoing Phase 1 CRB-402 study of bb21217, an investigational BCMA-directed CAR T cell therapy, were presented today at the meeting.

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"Building on our experience in multiple myeloma, Bristol Myers Squibb is dedicated to delivering the promise of CAR T cell therapy to patients with relapsed and refractory multiple myeloma," said Kristen Hege, senior vice president, Early Clinical Development, Hematology/Oncology and Cell Therapy, Bristol Myers Squibb. "Ide-cel and bb21217 are part of our broad cell therapy development program intended to bring transformative therapies to patients in need, and these data from different studies, including the longest follow-up for any anti-BCMA CAR T cell therapy from the original CRB-401 study and important analyses from our pivotal KarMMa trial, further underscore the potential of ide-cel to improve patient outcomes with durable responses and clinical benefits for patients with triple-class exposed multiple myeloma."

"The breadth of data presented at ASH (Free ASH Whitepaper) from across our studies underscores our commitment to the continued innovation of cell therapies for patients with multiple myeloma," said David Davidson, M.D., chief medical officer, bluebird bio. "We are encouraged by the longer-term results from the Phase 1 CRB-401 study, showing consistency with the depth and durability of responses observed in the Phase 2 KarMMa study, and reinforcing the role of ide-cel as an important potential therapeutic option for patients with triple-class exposed multiple myeloma. Additionally, we are pleased to see the updated results from the Phase 1 CRB-402 study, which continue to suggest promising response rates and durability. As had been hoped, early data also suggest that enrichment of bb21217 for memory-like T cells may be associated with sustained response. We look forward to presenting additional data from across our ide-cel and bb21217 development programs in the future as we work to transform the treatment landscape for patients living with this devastating disease."

Updated Results from CRB-401 Study of Ide-cel

In the Phase 1 CRB-401 study, 62 patients with heavily pretreated relapsed and refractory multiple myeloma were treated with ide-cel across dose levels of 50, 150, 450, or 800 × 106 CAR positive T cells (Presentation #131). The primary endpoint was safety, and secondary and exploratory endpoints included response rates, PFS, OS, and minimal residual disease (MRD).

Safety remained consistent with previously reported results from CRB-401. The most frequent adverse events (AEs) were neutropenia (92%), cytokine release syndrome (CRS; 76%), anemia (76%), and thrombocytopenia (74%). The most frequent Grade 3/4 AEs were neutropenia (89%), leukopenia (61%), anemia (57%), and thrombocytopenia (57%). Most CRS events were Grade 1 or 2. Four patients (7%) had Grade 3 CRS; there were no Grade 4 or 5 CRS events reported.1

Among 62 patients treated with ide-cel in this study, the overall response rate (ORR) was 76%, including 24 patients (39%) who achieved a complete response (CR). The median duration of response (DoR) was 10.3 months. Median PFS was 8.8 months and median OS was 34.2 months, with a median follow-up of 14.7 months. Full results from the CRB-401 study will be presented today in an oral presentation (Presentation #131).1

"The CRB-401 study continues to demonstrate the potential of ide-cel to provide deep and durable responses for heavily pre-treated relapsed and refractory multiple myeloma patients," said Yin Lin, M.D., Ph.D., presenting author, associate professor of hematology at Mayo Clinic. "This longer-term data is also important as it reflects a meaningful median duration of response for hard-to-treat patients, further highlighting the importance of ide-cel as a potential innovative treatment for patients with significant unmet treatment needs."

Analyses of Pivotal KarMMa Study: Subgroup Analyses of Ide-cel Outcomes in High-Risk and Elderly Patients and Health-Related Quality of Life

Ide-cel demonstrated deep and durable responses in the pivotal Phase 2 KarMMa study of patients with triple-class exposed relapsed and refractory multiple myeloma. A subgroup analysis was conducted to assess outcomes of treatment with ide-cel across target dose levels of 150 to 450 × 106 CAR positive T cells in patients with poor prognosis, including those with extramedullary disease, high-risk cytogenetics, and high tumor burden.

In the analysis of 128 patients, ide-cel demonstrated deep and durable responses across the majority of subgroups, including those with the highest risk. The ORR and CR rate were ≥65% and ≥20%, respectively, for the majority of high-risk subgroups. Additionally, in the majority of the high-risk subgroups, the median DoR was >9.2 months and the median PFS was >7.5 months. Results will be presented in a poster presentation on Monday, December 7 (Presentation #3234).2

A separate subgroup analysis was conducted to evaluate the outcomes of treatment with ide-cel in elderly patients (Presentation #1367). Multiple myeloma occurs most commonly among the older population, with a median age of 69 at diagnosis. Advanced age has been shown to negatively affect prognosis and limit treatment options.3

Of the 128 patients treated with ide-cel in the KarMMa study, 45 patients (35%) were aged ≥65 years and 20 patients (16%) were aged ≥70 years. Response rates for both age groups were comparable and consistent with the overall ide-cel treated population, across all target dose levels, with ORRs of 84% to 90% and CR rates of 31% to 35%.3

Likewise, median DoR among responders in both age groups (10.7 months in patients aged ≥65 years and 11.0 months in patients aged ≥70 years) was similar to that of the overall ide-cel treated population. Median PFS was 8.6 months (95% CI, 4.9-12.2) in patients aged ≥65 years and 10.2 months (95% CI, 3.1-12.3) in patients aged ≥70 years. Additionally, no new safety signals were observed.3

In an analysis of the impact of ide-cel treatment on health-related quality of life (HRQoL) measures in patients with relapsed and refractory multiple myeloma from the KarMMa study, ide-cel was associated with clinically meaningful QoL benefits without compromising any HRQoL domains (Presentation #437). Patients demonstrated a clinically meaningful improvement in most functioning and symptom scores from baseline to Month 3 through 15, with statistical significance (p<0.05) reached at various time points for different subscales throughout the follow-up period. Full results from the HRQoL analysis will be presented tomorrow, Sunday, December 6, in an oral presentation (Presentation #437).4

Phase 1 CRB-402 Study of bb21217

Updated safety and efficacy results from the ongoing Phase 1 study (CRB-402) of bb21217, an investigational BCMA-directed CAR T cell therapy being studied in patients with relapsed and refractory multiple myeloma, were also presented today in an oral presentation (Presentation #130). bb21217 uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention of increasing the in vivo persistence of CAR T cells.

As of the September 1, 2020 cutoff date, 69 patients were treated with bb21217 and updated results include new data following the introduction of a manufacturing process change. The study has completed enrollment and follow-up is ongoing as data continue to mature and the durability of response at the RP2D is assessed.5

About Ide-cel

Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 (4-1BB) and CD3-ζ chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Bristol Myers Squibb and bluebird bio’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio.

Ide-cel is not approved for any indication in any geography.

About bb21217

bb21217 is an investigational BCMA-targeted CAR T cell therapy that uses the ide-cel CAR molecule and is cultured with the PI3 kinase inhibitor (bb007) to enrich for T cells displaying a memory-like phenotype with the intention of increasing the in vivo persistence of CAR T cells. bb21217 is being studied for patients with multiple myeloma in partnership between bluebird bio and Bristol Myers Squibb.

The companies’ clinical development program for bb21217 includes the ongoing Phase 1 CRB-402 study. CRB-402 is the first-in-human study of bb21217 in patients with relapsed and refractory multiple myeloma (RRMM), designed to assess safety, pharmacokinetics, efficacy and duration of effect. CRB-402 is a two-part (dose escalation and dose expansion), open-label, multi-site Phase 1 study of bb21217 in adults with RRMM. A total of 69 patients have been treated with bb21217 and the study has completed enrollment. For more information visit: clinicaltrials.gov using identifier NCT03274219.

bb21217 is not approved for any indication in any geography.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming people’s lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.