The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) with the nonconvalent Bruton tyrosine kinase (BTK) inhibitor, LOXO-305, resulted in impressive and durable response rates, according to results of a phase 1/2 study presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“There was a near-universal tumor reduction, regardless of prior BTK inhibitors or molecular mutations,” Anthony R. Mato, MD, of Memorial Sloan Kettering Cancer Center in NYC, and presenter of the study, said.

The multicenter, phase 1/2 BRUIN trial ( Identifier: NCT03740529) treated 323 patients with B-cell malignancies with different dose levels of LOXO-305. Patients had received at least 2 prior therapies. The primary endpoint was maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). The present efficacy analysis included the 170 patients with CLL/SLL and the safety analysis included all 323 patients.

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In the CLL/SLL cohort, the median age of patients at baseline was 69 years, and 36% of patients were female. The median number of prior therapies was 4 (range, 1-10), including 86% of patients who had received a prior BTK inhibitor, 21% had received a PI3K inhibitor, and 34% had received venetoclax. Most patients had disease with high-risk features, including 25% with a 17p deletion, 30% with a TP53 mutation, and 88% with unmutated IGHV.

During a median follow-up of 6 months, the objective response rate (ORR) was 63%; however, the response deepened over time, with the ORR at 86% among patients with a follow-up of at least 10 months. The ORR was similar regardless of the presence of BTK C481 mutations, prior progression with a BTK inhibitor or other therapies, or number of prior lines of treatment. Responses were ongoing among 94% of responding patients.

“While duration of response and [progression-free survival] were encouraging, we note a relatively short median follow-up, and additional follow-up will be needed to confirm these results,” Dr Mato said.

There were no dose-limiting toxicities and the MTD was not reached. The most common treatment-emergent adverse events (TEAEs) were fatigue and diarrhea. The rate of grade 3 TEAEs was low at less than 3% and there were no grade 4/5 events. The rate of discontinuation due to treatment-related AEs was 1.5%.

Dr Mato concluded that “LOXO-305 is well tolerated and exhibits promising efficacy in heavily pretreated CLL/SLL patients.”

Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.


Mato AR, Pagel JM, Coombs CC, et al. LOXO-305, a next generation, highly selective, non-covalent BTK inhibitor in previously treated CLL/SLL: results from the phase 1/2 BRUIN study. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 542.