A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL

STATUS

Recruiting
End date

Oct 27, 2023
participants needed

860
sponsor

Loxo Oncology, Inc.

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Updated on 4 October 2022

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renal function

anemia

chronic lymphocytic leukemia

rituximab

measurable disease

thrombocytopenia

venetoclax

blood transfusion

diffuse large b-cell lymphoma

renal function tests

r-chop

btk inhibitor

chronic lymphocytic leukemia refractory

b-cell small lymphocytic lymphoma

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.

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.

Details

Condition	Chronic Lymphocytic Leukemia, Waldenstrom Macroglobulinemia, Mantle Cell Lymphoma, Marginal Zone Lymphoma, B-cell Lymphoma, Small Lymphocytic Lymphoma
Treatment	Rituximab, venetoclax, R-CHOP, LOXO-305, Pirtobrutinib
Clinical Study Identifier	NCT03740529
Sponsor	Loxo Oncology, Inc.
Last Modified on	4 October 2022

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Eligibility		Yes	No	Not Sure
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)

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A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL