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Clinical Trials Exploring BTK

LOXO-305

An investigational, selective non-covalent Bruton's tyrosine kinase (BTK) inhibitor with preclinical potency against both wild-type and cysteine-481–mutated BTK (C481S) and improved selectivity compared with other BTK inhibitors.

Exploring BTK

For more information, call 1-855-LOXO-305 or email clinicaltrials@loxooncology.com

NCT03740529 open_in_new

A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or B-cell non-Hodgkin’s Lymphoma (NHL)

This is a phase 1/2, open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, and overall response rate of LOXO-305 in patients with previously treated CLL/SLL, Waldenström’s macroglobulinemia (WM)/mantle cell lymphoma (MCL)/marginal zone lymphoma (MZL), follicular lymphoma, diffuse large B-cell lymphoma, or other B-cell NHL who have failed or are intolerant to the standard of care.

See Trial Information and Study Locations

About BTK

BTK, one of the 5 members of the Tec family of non-receptor tyrosine kinases, plays a critical role in oncogenic signaling.1 BTK is a cytoplasmic tyrosine kinase, and its activation results in downstream signaling that controls nuclear factor-κB, which is essential for normal B-cell function.1,2 BTK plays a critical role in the proliferation and survival of leukemic B-cells and is implicated in various B-cell malignancies including CLL, MZL, MCL, and WM.1,3

About BTK inhibition

Covalent BTK inhibitors, like Imbruvica® (ibrutinib) and Calquence® (acalabrutinib), are currently approved for treating patients with B-cell malignancies.4,5 Both agents potently inhibit BTK by forming an irreversible, covalent bond with the cysteine residue at position 481 (C481) in the adenosine triphosphate pocket of the BTK.6-8 Their long-term efficacy can be limited by acquired resistance and intolerance to therapy.8,9

For additional information about the LOXO-305 clinical trial, please refer to clinicaltrials.gov.

Interested physicians and patients may contact the Loxo Oncology BTK Physician and Patient Clinical Trial Hotline at +1-855-LOXO-305 or email clinicaltrials@loxooncology.com.

Policy for Access to Investigational Agents

Loxo Oncology is committed to helping patients who have not responded to available therapies and may benefit from its investigational therapies. Loxo Oncology's Policy for Access to Investigational Agents describes the principles and government regulations that the company will follow when considering a request.

    References:
  1. Pal Singh S, Dammeijer F, Hendriks RW. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer. 2018; 17:57-018-0779-z
  2. Bajpai UD, Zhang K, Teutsch M, et al. Bruton's tyrosine kinase links the B cell receptor to nuclear factor κB activation. J Exp Med. 2000;191(10):1735-1744.
  3. Cinar M, Hamdani F, Mo Z, et al. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis. Leuk Res. 2013;37(10):1271-1277.
  4. Imbruvica® Prescribing Information. Pharmacyclics LLC; 2018.
  5. Calquence® Prescribing Information. Astra Zeneca; 2017.
  6. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.
  7. Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): A covalent bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240-252.
  8. Mertens D, Stilgenbauer S. Ibrutinib-resistant CLL: unwanted and unwonted! Blood 2017;129(11):1407-1408.
  9. Woyach JA, Furman RR, Liu TM, et al. Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib. N Engl J Med. 2014;370(24):2286-2294.
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For more information, call +1-855-LOXO-305
or email clinicaltrials@loxooncology.com