Bristol Myers Squibb announced the first disclosure of primary analysis results from the high-risk, second-line cohort of TRANSCEND FL, an open-label, global, multicenter, Phase 2, single-arm study evaluating Breyanzi® (lisocabtagene maraleucel, liso-cel) in patients with relapsed or refractory follicular lymphoma (FL) (Oral Presentation #602). TRANSCEND FL is the largest clinical trial to date to evaluate a CAR T cell therapy in patients with relapsed or refractory indolent non-Hodgkin lymphoma, including FL. Additionally, the company presented long-term data from the TRANSCEND CLL 004 study evaluating Breyanzi in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) with 24-month follow-up (Oral Presentation #330). These data are being featured in oral presentations at the 2023 American Society of Hematology (ASH) Annual Meeting, from December 9-12, with the TRANSCEND FL 2L oral presentation selected as part of the 2024 Highlights of ASH for lymphoma.
“With additional data for Breyanzi across our TRANSCEND clinical trials, we continue to see its potential best-in-class and best-in-disease profile in follicular lymphoma, delivering clinically meaningful benefit and improved outcomes for patients with high unmet need,” said Anne Kerber, M.D., senior vice president, Head of Late Clinical Development, Hematology, Oncology, Cell Therapy (HOCT), Bristol Myers Squibb. “At Bristol Myers Squibb, we have an unwavering commitment to advancing innovative treatments. The breadth of data we are presenting at ASH this year for Breyanzi, including the first positive studies for a CD19-directed CAR T in follicular lymphoma and chronic lymphocytic leukemia, reinforces the significant progress that we are making toward bringing the promise of cell therapy to more patients.”
Results from TRANSCEND FL will be discussed with health authorities. A supplemental Biologics License Application for Breyanzi in relapsed or refractory CLL based on results from TRANSCEND CLL 004 is currently under review by the U.S. Food and Drug Administration with a target action date of March 14, 2024.
Bristol Myers Squibb (BMS) has the broadest ongoing cell therapy development program in CD19-positive malignancies with Breyanzi, which also includes trials investigating its use in patients with relapsed/refractory mantle cell lymphoma (MCL). Results from the primary analysis of the MCL cohort of TRANSCEND NHL 001 were simultaneously published in Journal of Clinical Oncology. BMS thanks the patients and investigators participating in the TRANSCEND clinical trials.
Results from TRANSCEND FL and Patient-Reported Outcomes
In the TRANSCEND FL clinical trial, 130 patients with relapsed or refractory follicular lymphoma (FL) were enrolled and treated with Breyanzi in the second-line and third-line plus settings. Patients received treatment with Breyanzi at a target dose of 100 x 106 CAR-positive viable T cells. TRANSCEND FL is the largest clinical trial evaluating a CAR T cell therapy in relapsed or refractory FL, and the first trial to report outcomes for a CAR T in second-line, high-risk FL, with results generally consistent with the efficacy and safety results observed in third-line FL.
- In patients with high-risk relapsed or refractory FL treated with Breyanzi in the second-line setting who were evaluable for efficacy (n=23) with a median on-study follow-up of 18.1 months (range: 1.0–26.8), Breyanzi elicited significant responses in nearly all patients, with all responders achieving a complete response (CR).
- The overall response rate (ORR), the study’s primary endpoint, and CR rate were 95.7% (n=22/23; 95% CI: 78.1-99.9; one-sided p<0.0001). With a median follow-up of 16.8 months, median duration of response (DOR) was not reached (95% CI: 19.3-NR).
- The probability of patients remaining in response at 12 months was 89.8%. Median progression-free survival (PFS) was also not reached (95% CI: 20.2-NR), with a PFS rate of 91.3% at 12 months.
Breyanzi continued to exhibit a manageable and predictable safety profile with no new safety signals observed and low rates of severe cytokine release syndrome (CRS) and neurologic events (NE). Any-grade CRS occurred in 52.2% of patients, with no grade >3 CRS reported. Any-grade NEs were reported in 17.4% of patients, with Grade 3 NEs occurring in 4.3% of patients and no Grade 4/5 NEs reported. All cases of CRS and NEs were managed to resolution.
“Despite high initial response rates to front-line treatment, the majority of patients with follicular lymphoma relapse with prognosis worsening, leaving them in need of a treatment option that will provide significant and lasting responses,” said Franck Morschhauser, M.D., Ph.D., lead investigator and Professor of Hematology at Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France. “Based on results from TRANSCEND FL for liso-cel as a second-line treatment option, the vast majority of patients achieved a complete response, with probability of overall responses lasting at least 12 months. Additionally, the safety profile for liso-cel continued to be manageable, showing the clinically meaningful value of using this differentiated treatment option for patients with relapsed or refractory follicular lymphoma after failure of front-line therapy.”
Patient-reported outcomes (PROs) from TRANSCEND FL are also being presented (Oral Presentation #668), representing the first disclosure of PRO data for a CAR T cell therapy in relapsed or refractory FL. Based on an exploratory analysis, the majority of patients with second- or third-line relapsed or refractory FL reported clinically significant improvements in quality of life, disease symptoms, and functioning after being treated with Breyanzi. Those receiving Breyanzi in the second-line setting generally demonstrated greater and faster meaningful improvements in most primary domains, compared to those who received Breyanzi in the third-line setting, including role and cognitive functioning, fatigue, pain, and Functional Assessment of Cancer Therapy Lymphoma scores.
SOURCE: BusinessWire
