Loxo Oncology at Lilly Announces Updated Data from the Phase 1/2 BRUIN Clinical Trial for LOXO-305 in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma at the American Society of Hematology Annual Meeting
INDIANAPOLIS, Dec. 7, 2020 /PRNewswire/ -- Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), today announced clinical data from the LOXO-305 global Phase 1/2 BRUIN clinical trial in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). LOXO-305 is an investigational, highly selective, non-covalent Bruton's tyrosine kinase (BTK) inhibitor. These data are being presented in an oral presentation at the 2020 American Society of Hematology (ASH) Annual Meeting (abstract 542).
"The data presented at ASH reveal an incredibly encouraging and consistent safety and efficacy profile for LOXO-305 in heavily pre-treated CLL and SLL patients, regardless of previous therapies, reasons for discontinuations of those therapies, or presence of resistance mutations", said Anthony Mato, M.D., director of the CLL Program at Memorial Sloan Kettering Cancer Center and the presenting author. "We are increasingly in need of new therapies for patients that have been previously treated with a covalent BTK inhibitor, and LOXO-305 may allow us to continue treating patients in the same biologic class before attempting more complicated therapeutic approaches."
"The LOXO-305 data continue to surpass our expectations, and we are very excited for what these data could mean for patients with CLL and SLL", said David Hyman, M.D., chief medical officer of Loxo Oncology at Lilly. "These emerging data further substantiate our thesis that the drug's reversible binding mode, high selectivity, and robust pharmacology offer a differentiated treatment option across B-cell leukemias and lymphomas. We are eager to initiate a Phase 3 program in 2021."
Key Data Presented at ASH
As of September 27, 2020, 323 patients were enrolled in the study, including 170 with CLL/SLL, 61 with mantle cell lymphoma (MCL), 26 with Waldenström's macroglobulinemia, and 66 with other B-cell lymphomas. The CLL/SLL patients had received a median of three prior lines of therapy with 86% receiving a prior BTK inhibitor, 90% an anti-CD20 antibody, 82% chemotherapy, 34% venetoclax, 21% a PI3K inhibitor, 6% CAR-T therapy and 2% an allogeneic transplant.
Pharmacokinetic analyses during the dose escalation demonstrated consistent dose-proportional exposures with low inter-patient variability across the entire dosing range of 25mg to 300mg daily. Doses of 100mg QD and greater exceeded BTK IC90 target coverage for the entirety of the dosing interval. Responses were observed starting at the first dose level.
The efficacy data presented at ASH are based on investigator response assessments. Patients were considered efficacy-evaluable if they had at least one post-baseline response assessment or if they discontinued treatment prior to their first post-baseline response assessment. In 139 efficacy-evaluable patients with CLL/SLL treated across all dose levels, 88 responded including 69 partial responses (PR), 19 partial responses with ongoing lymphocytosis (PR-L), 45 stable disease (SD), one progressive disease (PD), five discontinued prior to their first response assessment and were considered non-evaluable (NE), resulting in an overall response rate (ORR) of 63% (95% CI: 55-71). The ORR was consistent in various subsets of patients, including:
As of the data cut-off, 88% of all CLL/SLL patients remain on LOXO-305. Median follow-up for efficacy-evaluable CLL/SLL patients was six months. Of the 88 responding CLL/SLL patients, all except five remain on therapy (four progressed and one achieved a PR and electively discontinued to pursue a transplant). The longest-followed responding patient continues on treatment at 17.8 months.
Safety data were presented for the entire enrolled BRUIN population. Across all 323 patients enrolled in the study, the most commonly reported adverse events, regardless of attribution, were fatigue (20%), diarrhea (17%), and contusion (13%). In addition, rates of two adverse events commonly associated with BTK inhibitors, atrial arrythmias and hemorrhage, were low, experienced by two patients and one patient respectively, and considered by investigators as unrelated to LOXO-305. Dose interruptions, reductions and permanent discontinuations for drug-related adverse events were observed in 8%, 2.2%, and 1.5% of patients, respectively. No dose limiting toxicities were reported and a maximum tolerated dose (MTD) was not reached.
LOXO-305 Development Program Update
In addition to the previously announced Phase 3 MCL trial, Loxo Oncology at Lilly is preparing to initiate two global, randomized, Phase 3 clinical trials in BTK pre-treated patients with CLL/SLL. The trials will explore LOXO-305, alone and in combination as follows:
In addition, Loxo Oncology at Lilly is planning to study LOXO-305 in treatment-naïve CLL/SLL, including a global, randomized Phase 3 superiority clinical trial to study LOXO-305 versus ibrutinib, expected to start later in 2021.
About the BRUIN Trial
About Loxo Oncology at Lilly
About Eli Lilly and Company
Disclosure: Dr. Mato has provided consulting and advisory services to Loxo Oncology at Lilly and Eli Lilly and Company.
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Lilly's LOXO-305 for the potential treatment of previously treated chronic lymphocytic leukemia, small lymphocytic lymphoma and non-Hodgkin lymphoma and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that studies will complete as planned, that future study results will be consistent with the results to date, or that LOXO-305 will receive regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
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