The Oncology Institute Enrolls Patients With CLL in Phase 3 BRUIN-CLL-314 Trial

Partners | <b>The Oncology Institute</b>

Treatment with the investigational Bruton’s tyrosine kinase inhibitor, pirtobrutinib, will be compared with ibrutinib treatment in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma in a phase 2 study.

The first and second patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who are patients of The Oncology Institute (TOI) have been dosed with pirtobrutinib (LOXO-305) in the phase 3 BRUIN-CLL-314 clinical trial (NCT05254743).1

“We at TOI are extremely proud of our role in this important clinical trial,” says Yale Podnos, MD, MPH, FACS, chief medical officer of The Oncology Institute, in a press release. “New, effective treatments can’t be made available to the public without this important research. We look forward to working with the scientific community to continue to be at the forefront of cutting-edge oncology research.”

Pirtobrutinib is an investigational Bruton’s tyrosine kinase (BTK) inhibitor. According to TOI, the agent mechanism of action allows for higher BTK inhibition and selectivity and reduces off-target adverse events. Pirtobrutinib was developed for the treatment of patients with relapsed CLL to address the widespread concern around the development of drug resistance in patients with CLL.

In the BRUIN-CLL-314 study, patients CLL/SLL will be assessed on treatment with either oral pirtobrutinib or oral ibrutinib (Imbruvica) to determine the efficacy and safety of pirtobrutinib. The primary end point being evaluated in the study is the percentage of patients with a complete response (CR) or partial response (PR). The study’s secondary end points include event-free survival, progression-free survival, and time to worsening of CLL- or SLL-related symptoms.2

Patients are eligible to enroll given they have a confirmed diagnosis of CLL/SLL, an ECOG performance status of 0-2, adequate organ function, platelets greater than or equal to ≥ 50 x 10⁹/liter (L), hemoglobin ≥ 8 grams/deciliter (g/dL), and absolute neutrophil count ≥ 0.75 x 10⁹/L, as well as adequate kidney function.

The study excludes patients who have had prior exposure to a BTK inhibitor, are concurrently using an investigational agent or anticancer therapy, are using ≥ 20 mg prednisone daily or an equivalent dose of steroid at the time of the first dose of study drug, receiving vaccination with a live vaccine within 28 days before randomization, or receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor which cannot be stopped within 3-5 half-lives of the CYP3A inhibitor therapy before the start of the study. Patients with a history of a certain disease that may interfere with the outcome of treatment are ineligible for the study.

Moreover, the study excludes patients with active uncontrolled auto-immune cytopenia, significant cardiovascular disease, active hepatitis B or hepatitis C, active cytomegalovirus infection, active uncontrolled systemic bacterial, viral, or fungal infection, and other conditions that may affect the outcome of study treatment.

Patients who meet the eligibility criteria are actively being recruited at sites 26 sites across the United States. Of note, TOI hematologists/oncologists including Merrill Shum, MD of Whittier, CA, and John Khoury, MD of Glendale, CA, have enrolled patients and are actively recruiting. The lead investigator for the BRUIN-CLL-314 study at TOI locations is the founder of the company, Richy Agajanian, MD.1

REFERENCES:

1. The Oncology Institute enrolls nation’s first two patients in a phase 3 open-label, randomized clinical trial of pirtobrutinib. News release. The Oncology Institute. September 29, 2022. Accessed October 18, 2022. https://bit.ly/3ThQWWH

2. A study of pirtobrutinib (LOXO-305) versus ibrutinib in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (BRUIN-CLL-314). Clinicaltrials.gov. Updated October 12, 2022. Accessed October 18, 2022. https://clinicaltrials.gov/ct2/show/NCT05254743?term=BRUIN-CLL-314&draw=2&rank=1