Brief Title
A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL
Official Title
A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)
Brief Summary
This is an open-label, multi-center Phase 1/2 study of oral LOXO-305 (pirtobrutinib) in
patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.
Detailed Description
This study includes 3 parts: Phase 1 (pirtobrutinib monotherapy dose escalation and dose
expansion), Phase 1b (pirtobrutinib combination therapy dose expansion), and Phase 2
(pirtobrutinib monotherapy dose expansion). In Phase 1, patients will be enrolled using an
accelerated titration design. The starting dose of pirtobrutinib in oral tablet form is 25
mg/day (e.g., 25 mg once daily [QD]). Once the MTD and/or RP2D is identified in Phase 1 dose
escalation, enrollment will continue to Phase 1 dose expansion and can commence to Phase 1b
(Arms A and B). For Phase 2, patients will be enrolled to one of seven Phase 2 dose expansion
cohorts depending on tumor histology and prior treatment history. Cycle length will be 28
days.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum Tolerated Dose (MTD)
Secondary Outcome
To determine the safety profile and tolerability of pirtobrutinib including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events.
Condition
Chronic Lymphocytic Leukemia
Intervention
Pirtobrutinib
Study Arms / Comparison Groups
Phase I Dose Escalation (Pirtobrutinib Monotherapy)
Description: Dose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
860
Start Date
November 16, 2018
Completion Date
April 2024
Primary Completion Date
April 2024
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed CLL/SLL, WM, or NHL intolerant to either ≥ 2 prior standard
of care regimens given in combination or sequentially OR have received 1 prior BTK
inhibitor-containing regimen when a BTK inhibitor is approved as first line therapy
(Phase 1) OR with prior treatment defined by phase 2 cohort (Phase 2 Patients only).
- Adequate hematologic function (Phase 1 and 1b Patients only).
- Responsive to transfusion support if given for thrombocytopenia or anemia (Phase 1 and
1b Patients only).
- Histologically confirmed relapsed/recurrent CLL in whom venetoclax is appropriate
standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm A Patients
only).
- Histologically confirmed relapsed/refractory CLL in whom venetoclax + rituximab is
appropriate standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm
B Patients only).
- Eastern Cooperative Oncology Group (ECOG) 0-2.
- Adequate hepatic and renal function.
- Ability to receive study drug therapy orally.
- Willingness of men and women of reproductive potential (defined as following menarche
and not postmenopausal [and 2 years of non-therapy-induced amenorrhea] or surgically
sterile) to observe conventional and effective birth control.
Exclusion Criteria:
- Investigational agent or anticancer therapy within 5 half-lives or 14 days, whichever
is shorter, prior to planned start of specified study therapy except antineoplastic
and immunosuppressant monoclonal antibody treatment must be discontinued a minimum of
4 weeks prior to the first dose of pirtobrutinib. In addition, no concurrent systemic
anticancer therapy is permitted.
- Major surgery within 4 weeks prior to planned start of specified study therapy.
- Radiotherapy with a limited field of radiation for palliation within 7 days of the
first dose of study treatment.
- Pregnancy or lactation.
- Patients requiring therapeutic anticoagulation with warfarin.
- Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2
or greater at the time of starting study treatment except for alopecia.
- History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen
receptor-modified T-cell (CAR-T) therapy within the past 60 days (180 days before the
PK trigger) prior to planned start of specified study therapy.
- Known central nervous system (CNS) involvement by systemic lymphoma. Patients with
previous treatment for CNS involvement who are neurologically stable and without
evidence of disease may be eligible and enrolled to phase 2 Cohort 7 if a compelling
clinical rationale is provided by the Investigator and with documented Sponsor
approval.
- Active uncontrolled auto-immune cytopenia where new therapy introduced or concomitant
therapy escalated within the 4 weeks prior to study enrollment is required to maintain
adequate blood counts.
- Clinically significant, uncontrolled cardiac, cardiovascular disease or history of
myocardial infarction within 6 months prior to planned start of pirtobrutinib.
- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
- Patients who have tested positive for human immunodeficiency virus (HIV) are excluded.
For patients with unknown HIV status, HIV testing will be performed at Screening and
result should be negative for enrollment.
- Clinically significant active malabsorption syndrome.
- Current treatment with certain strong CYP3A4 inhibitors or inducers and/or strong P-gp
inhibitors.
- For patients enrolled to phase 1b Arm A or B: Patients with prior treatment with
venetoclax or other BCL-2 inhibitors.
- Prior treatment with pirtobrutinib.
- Active second malignancy unless in remission and with life expectancy > 2 years.
- Known hypersensitivity to any component or excipient of pirtobrutinib.
- For patients enrolled to phase 1b Arm B: Patients with prior significant
hypersensitivity, allergy, or anaphylactic reaction to rituximab/biosimilar requiring
discontinuation.
- Patients with prior significant hypersensitivity to rituximab requiring
discontinuation, prior allergic or anaphylactic reaction to rituximab (Phase 1b Arm B
Patients only).
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Donald Tsai, MD, PhD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03740529
Organization ID
LOXO-BTK-18001 (BRUIN)
Secondary IDs
2018-003340-24
Responsible Party
Sponsor
Study Sponsor
Loxo Oncology, Inc.
Collaborators
Eli Lilly and Company
Study Sponsor
Donald Tsai, MD, PhD, Study Director, Loxo Oncology
Verification Date
March 2023