The purpose of this study is to find out whether the study drug, LOXO-338, is safe and effective in patients with advanced blood cancer. Patients must have already received standard therapy. The study may last up to approximately 3 years.
This study will be conducted in 2 parts. Part 1 will evaluate LOXO-338 as monotherapy. If safety and initial evidence of efficacy of LOXO-338 monotherapy are confirmed, part 2 will evaluate the combination of LOXO-338 with the highly selective, noncovalent Bruton's tyrosine kinase (BTK) inhibitor, pirtobrutinib (LOXO-305).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Oral
Oral
The University of Arizona Cancer Center
Tucson, Arizona, United States
Part 1 - To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of oral LOXO-338
Measured by the number of patients with dose-limiting toxicities (DLTs)
Time frame: Cycle 1 (28 Days)
Part 1 - To determine the effect of LOXO-338 on response rates
Measured by the appropriate disease specified response criteria as appropriate to tumor type
Time frame: Estimated up to 2 years
Part 2 - To determine the safety and tolerability of LOXO-338 when given in combination with pirtobrutinib
Measured by the number of patients with dose-limiting toxicities (DLTs)
Time frame: Cycle 2 (28 Days)
Part 1 - To characterize the pharmacokinetics (PK) properties of LOXO-338: Area under the plasma concentration versus time curve (AUC)
PK: AUC of LOXO-338
Time frame: Predose up to 24 hours postdose
Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax)
PK: Cmax of LOXO-338
Time frame: Predose up to 24 hours postdose
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR)
ORR
Time frame: Estimated up to 2 years
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS)
PFS
Time frame: Estimated up to 2 years
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City of Hope National Medical Center
Duarte, California, United States
University of California San Francisco, Medical Center at Paranassus
San Francisco, California, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Emory University
Atlanta, Georgia, United States
Indiana Blood & Marrow Transplantation (IBMT)
Indianapolis, Indiana, United States
University of Kansas Medical Center
Westwood, Kansas, United States
Tufts Medical Center
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
...and 13 more locations
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP)
TTP
Time frame: Estimated up to 2 years
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR)
DOR
Time frame: Estimated up to 2 years
Part 2 - To characterize the pharmacokinetics (PK) properties of LOXO-338 in combination with pirtobrutinib: Area under the plasma concentration versus time curve (AUC)
PK: AUC of LOXO-338 alone and in combination with pirtobrutinib
Time frame: Predose up to 24 hours postdose
Part 2 - To characterize the PK properties of LOXO-338 and in combination with pirtobrutinib: Maximum drug concentration (Cmax)
PK: Cmax of LOXO-338 alone and in combination with pirtobrutinib
Time frame: Predose up to 24 hours postdose
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on overall response rate (ORR)
ORR
Time frame: Estimated up to 2 years
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on progression-free survival (PFS)
PFS
Time frame: Estimated up to 2 years
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on time-to-progression (TTP)
TTP
Time frame: Estimated up to 2 years
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on duration of response (DOR)
DOR
Time frame: Estimated up to 2 years