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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
803
Maximum Tolerated Dose (MTD)
Phase I
Time frame: Up to 24 Months
Recommended dose for further study
Phase I
Time frame: Up to 24 Months
To assess the preliminary anti-tumor activity of pirtobrutinib based on ORR as assessed by an Independent Review Committee (IRC).
Phase II
Time frame: Up to 24 months
To evaluate the safety of pirtobrutinib in combination with venetoclax (Arm A) by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0
For Phase 1b
Time frame: Up to 24 Months
To evaluate the safety of pirtobrutinib in combination with venetoclax and rituximab (Arm B) by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0
For Phase 1b
Time frame: Up to 24 Months
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.
Phase I
Time frame: Up to 24 Months
To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.
Phase I
Time frame: Up to 24 Months
To assess the preliminary anti-tumor activity of pirtobrutinib based on overall response rate (ORR) as assessed by investigator.
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Mayo Clinic of Scottsdale
Scottsdale, Arizona, United States
Scripps Coastal Medical Center
San Diego, California, United States
University of California San Francisco, Medical Center at Paranassus
San Francisco, California, United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, United States
Mayo Clinic-Jacksonville
Jacksonville, Florida, United States
Florida Cancer Specialists ORLANDO/DDU
Lake Mary, Florida, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Florida Cancer Specialists
Sarasota, Florida, United States
Emory Clinic
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
...and 46 more locations
Phase I
Time frame: Up to 24 Months
ORR as assessed by the Investigator.
Phase II
Time frame: Up to 24 Months
Best overall response (BOR) as assessed by the Investigator and IRC.
Phase II
Time frame: Up to 24 Months
Duration of response (DOR) as assessed by the Investigator and IRC.
Phase II
Time frame: Up to 24 Months
Progression free survival (PFS) as assessed by the Investigator and IRC.
Phase II
Time frame: Up to 24 Months
Overall survival (OS).
Phase II
Time frame: Up to 24 Months
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
Phase II
Time frame: Up to 24 Months
To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.
Phase II
Time frame: Up to 24 Months
To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.
For Phase 1b
Time frame: Up to 24 months
To assess the preliminary anti-tumor activity of pirtobrutinib in combination based on overall response rate (ORR) as assessed by investigator.
For Phase 1b
Time frame: Up to 24 months
Symptomatic Response: Change from Baseline in Mantle Cell Lymphoma (MCL)-related symptoms selected from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library
Individual EORTC symptom scores range from 1 (not at all) to 4 (very much) with higher scores representing more severe symptom severity.
Time frame: Baseline, End of Treatment (Estimated Up to 24 Months)
Functional Response: Change from Baseline in Physical Functioning as Measured by Physical Functioning Scale from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ)
EORTC physical function item scores range from 1 (not at all) to 4 (very much) with higher scores indicating poorer functioning.The total EORTC physical functioning score ranges from 0-100 where a higher score indicates higher/healthier level of functioning.
Time frame: Baseline, End of Treatment (Estimated Up to 24 Months)