PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb (NYSE: BMY) today announced data from multiple studies evaluating lisocabtagene maraleucel (liso-cel), an investigational CD19-directed chimeric antigen receptor (CAR) T cell therapy, in relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), in relapsed or refractory mantle cell lymphoma (MCL), and in relapsed or refractory large B-cell lymphoma (LBCL) were presented at the 62^nd American Society of Hematology (ASH) Annual Meeting and Exposition. The data include longer-term follow-up from the Phase 1 TRANSCEND CLL 004 study in a cohort of patients with relapsed or refractory CLL and SLL treated with liso-cel as monotherapy and initial results from the combination cohort with ibrutinib, and safety and preliminary efficacy results from TRANSCEND NHL 001 in the cohort of patients with relapsed or refractory MCL treated with liso-cel. Additionally, initial results from the OUTREACH study evaluating outcomes of treatment with liso-cel for patients with relapsed or refractory LBCL across inpatient and outpatient settings were presented.

“In our mission to transform patients’ lives through science, we have established a diverse and comprehensive development program to understand the potential of liso-cel across both aggressive and indolent hematologic malignancies and sites of care,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Global Clinical Development, Hematology, Bristol Myers Squibb. “In addition, we continue to advance our cell therapy research to inform potential combination strategies with our CAR T cell therapies to optimize treatment outcomes for patients in need.”

Liso-cel in Combination with Ibrutinib and as Monotherapy in CLL/SLL: TRANSCEND CLL 004

In the Phase 1/2 TRANSCEND CLL 004 study, patients with relapsed or refractory CLL and SLL were enrolled in a cohort receiving liso-cel in combination with ibrutinib (Presentation #544). Nineteen patients started or continued ibrutinib treatment for >90 days at enrollment and were evaluated for safety and efficacy following liso-cel treatment.

Seventy-four percent of patients experienced any grade cytokine release syndrome (CRS) with one Grade 3 event. Median time to onset of CRS was 6.5 days (1-13) and median duration of CRS was 6 days (3-13). Any grade neurologic events (NEs) occurred in 32% of patients with three Grade 3 events. Median time to onset of NEs was 8 days (5-12) and median duration of NEs was 6.5 days (1-8).¹

With median follow-up of 10 months, liso-cel in combination with ibrutinib demonstrated high rates of response with 18 patients (95%) deriving an overall response, and 12 (63%) achieving a complete response. All responses were achieved by Day 30 following liso-cel treatment and among 18 patients with >6 months of follow-up, 89% maintained or improved their response from Day 30. Of 19 patients evaluable for minimal residual disease (MRD), 17 (89%) achieved undetectable MRD (uMRD) in blood by flow cytometry and 15 (79%) in bone marrow by next-generation sequencing (both with sensitivity 10⁴).¹

In a separate cohort of the Phase 1/2 TRANSCEND CLL 004 study, patients with relapsed or refractory CLL, including 83% of patients with high-risk disease, and patients who had progressed on prior therapy with ibrutinib, were enrolled to receive liso-cel as a monotherapy (Presentation #546). At median follow-up of 24 months, 23 patients were evaluable for safety and 22 patients were evaluable for efficacy.

In the 23 patients evaluated for safety, the safety profile for liso-cel was consistent with the known safety profile of liso-cel with no new late or delayed adverse events of concern emerging with longer follow-up. Seventy-four percent of patients experienced any grade CRS, with Grade >3 CRS occurring in 9% of patients. Median time to onset of CRS was three days (1-10) and median duration of CRS was 12 days (2-50). Any grade NEs occurred in 39% of patients, with 22% of patients experiencing Grade >3 NEs. Median time to onset of NEs was four days (2-21) and median duration of NEs was 20.5 days (6-50).²

Among the 22 patients evaluable for efficacy, the overall response rate was 82% (18/22). Complete responses were seen in 46% (10/22) of patients. By Day 30, 68% of patients (n=15) responded to therapy, and 27% had a deepening of response. At 12 months, 50% of patients remained in response and all seven patients who completed the 24-month follow-up maintained their response. The median duration of response was not reached (95% CI: 4.8 – NR) at median follow-up of 24 months and median progression-free survival was 18 months (95% CI: 3.0 – NR).²

“Patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma are often faced with a difficult treatment journey and many changes in therapy due to relapse,” said William G. Wierda, M.D., Ph.D., executive medical director and professor, Department of Leukemia, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center. “Results from TRANSCEND CLL 004 underscore the potential of liso-cel to deliver rapid, deep and durable responses as a monotherapy in heavily pretreated patients with difficult-to-treat disease and the potential of using liso-cel in combination with ibrutinib to provide high rates of overall response with a very manageable safety profile to address a significant unmet need for this disease.”

Safety and Efficacy of Liso-cel in Relapsed or Refractory MCL: TRANSCEND NHL 001

In the TRANSCEND NHL 001 study cohort of patients with relapsed or refractory MCL, including many with highly proliferative disease, 32 patients received liso-cel across dose levels of 50 x 10⁶ CAR positive T cells and 100 x 10⁶ CAR positive T cells (Presentation #118).

Sixteen patients (50%) experienced any grade CRS, including one Grade >3 event. Median time to CRS onset and resolution was six days (2‒10) and four days (2-9), respectively. Eleven patients (34%) experienced any grade NEs, all of which occurred in those who received the higher dose level, including four Grade >3 NEs. Median time to NE onset and resolution was eight days (2-25) and four days (1-27), respectively.³

Preliminary efficacy results showed that treatment with liso-cel resulted in high response rates with 84% of patients responding to treatment and 66% of patients achieving a complete response (CR). Overall, the median time to first complete or partial response was less than one month (0.95; range 0.9-2.0). Median duration of response was not reached with a median follow-up of 3.9 months (0.0-21.3).³

“Mantle cell lymphoma is an aggressive type of non-Hodgkin lymphoma and many patients relapse after initial therapies with limited remaining treatment options,” said M. Lia Palomba, M.D., Lymphoma Service and Center for Cellular Therapeutics, Memorial Sloan Kettering Cancer Center. “Initial results of liso-cel in MCL from TRANSCEND NHL 001 demonstrate the potential of this CAR T cell therapy to provide patients with high rates of response, representing a potentially important treatment option for these patients.”

Initial Results from the OUTREACH Study of Liso-cel in Relapsed or Refractory Large B-Cell Lymphoma (LBCL) Across Sites of Care

In the Phase 2 OUTREACH study, adults with relapsed or refractory LBCL were treated with liso-cel in the inpatient and outpatient settings at nonuniversity centers (Presentation #1196). The primary endpoint was incidence of Grade >3 CRS based on the Lee grading system, NEs, prolonged cytopenias through day 29 and infections. Secondary endpoints included safety and overall response rate (ORR).

Based on initial results from 46 patients treated with liso-cel (inpatient n=16; outpatient n=30) at data cutoff, patients were successfully treated and monitored in the inpatient and outpatient settings. Any grade CRS was reported in six (37.5%) patients treated in the inpatient setting and 13 (43%) patients treated in the outpatient setting, with no Grade >3 events reported. NEs were reported in five (31%) inpatients and nine (30%) outpatients, with one Grade >3 event in the inpatient group and two in the outpatient group. Median time to onset of CRS and NEs, respectively, was 2.5 (1–3) and 10 (3–16) days for inpatients and five (2–9) and nine (6–14) days for outpatients.⁴

Among efficacy-evaluable patients (n=44), 75% of inpatients achieved an overall response with 50% of patients achieving a complete response (CR), and 79% of outpatients achieved an overall response with 61% achieving a CR.⁴

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.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Juno Therapeutics, Inc. is a wholly owned subsidiary of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

Bristol Myers Squibb Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that lisocabtagene maraleucel (liso-cel), alone or in combination with ibrutinib, may not receive regulatory approval for the indications described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate or combination treatment for such indications described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2019, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

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References:

1. Wierda, WG., et al. TRANSCEND CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SS). American Society of Hematology Annual Meeting 2020. Presentation #544.
2. Siddiqi, T., et al., Updated Follow-Up of Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated with Lisocabtagene Maraleucel in the Phase 1 Monotherapy Cohort of TRANSCEND CLL 004, Including High-Risk and Ibrutinib-Treated Patients. American Society of Hematology Annual Meeting 2020. Presentation #546.
3. Palomba, ML., et al., Safety and Preliminary Efficacy in Patients with Relapsed/Refractory Mantle Cell Lymphoma Receiving Lisocabtagene Maraleucel in TRANSCEND NHL 001. American Society of Hematology Annual Meeting 2020. Presentation #118.
4. Godwin, JE., et al., Outcomes of Treatment with the CAR T Cell Therapy Lisocabtagene Maraleucel in the Nonuniversity Setting: Initial Results from the OUTREACH Study. American Society of Hematology Annual Meeting 2020. Presentation #1196.

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