Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LOXO-305 · 4 trials · 9 indications
ORR was assessed by an Independent Review Committee (IRC). It was estimated based on the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). Two-sided 95% CI was calculated using the exact binomial distribution. PAS consisted of participants with Central histologically confirmed non-blastoid MCL, with no CNS metastases and treated with prior chemoimmunotherapy and BTK inhibitor-containing regimen, measurable disease at baseline as assessed using Lugano criteria, and have received at least 1 dose of study drug.
AUC0-inf of LOXO-305 in plasma.
AUC0-inf of total radioactivity in plasma and whole blood.
AUC0-t of LOXO-305 in plasma.
AUC0-t of total radioactivity in plasma and whole blood.
Cmax of LOXO-305 in plasma.
Cmax of total radioactivity in plasma and whole blood.
Tmax of LOXO-305 in plasma.
Tmax of total radioactivity in plasma and whole blood.
t1/2 of LOXO-305 in plasma.
t1/2 of total radioactivity in plasma and whole blood.
CL/F of LOXO-305 in plasma.
Vz/F of LOXO-305 in plasma.
AUC0-inf of plasma LOXO-305 relative to AUC0-inf of plasma total radioactivity, expressed in ratio.
AUC0-inf of whole blood total radioactivity relative to AUC0-inf of plasma total radioactivity, expressed in ratio.
The urine sampling time points from pre-dose through 360 hours post-dose were used to assess this outcome.
The feces sampling time points from the 0 hour (i.e. time of dose) through 360 hours post-dose were used to assess this outcome.
The feces sampling time points from the 0 hour (i.e. time of dose) through 360 hours post-dose were used to assess this outcome.
The urine sampling time points from pre-dose through 360 hours post-dose were used to assess this outcome.
The metabolic profile of LOXO-305 following a single oral dose of \[14C\]-LOXO-305 was done to assess the presence of LOXO-305 and various metabolites (M1 to M4, M11, M12, M15 to M22) in plasma using high-performance liquid chromatography with radiochemical detection. Metabolites are identified by comparison with known standards (when available) and/or by liquid chromatography/tandem mass spectrometry analysis. The presence of any metabolite in a given matrix is indicated as '1' and absence from that matrix is indicated as '0'.
The metabolic profile of LOXO-305 following a single oral dose of \[14C\]-LOXO-305 was done to assess the presence of LOXO-305 and various metabolites (M1 to M4, M11, M12, M15 to M22) in urine using high-performance liquid chromatography with radiochemical detection. Metabolites are identified by comparison with known standards (when available) and/or by liquid chromatography/tandem mass spectrometry analysis. The presence of any metabolite in a given matrix is indicated as '1' and absence from that matrix is indicated as '0'.
The metabolic profile of LOXO-305 following a single oral dose of \[14C\]-LOXO-305 was done to assess the presence of LOXO-305 and various metabolites (M1 to M4, M11, M12, M15 to M22) in feces using high-performance liquid chromatography with radiochemical detection. Metabolites are identified by comparison with known standards (when available) and/or by liquid chromatography/tandem mass spectrometry analysis. The presence of any metabolite in a given matrix is indicated as '1' and absence from that matrix is indicated as '0'.
AUC0-inf of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
AUC0-inf of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
AUC0-inf of total radioactivity in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
AUC0-t of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
AUC0-t of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
AUC0-t of Total Radioactivity in Plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Cmax of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Cmax of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Cmax of Total Radioactivity in Plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Tmax of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Tmax of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Tmax of Total Radioactivity in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
t1/2 of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
t1/2 of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
t1/2 of Total Radioactivity in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
CL/F of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
Vz/F of LOXO-305 in plasma. The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
The absolute bioavailability expressed in ratio was calculated using the formula= AUC0-inf (oral) x Dose (IV) divided by AUC0-inf (IV) x Dose (oral) . The sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
CL of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Vz of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
Vss of \[14C\]-LOXO-305 in plasma. The sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
CLR of \[14C\]-LOXO-305 in urine collection. The urine sampling time points from pre-IV dose through 192 hours post-IV dose were used to assess this outcome.
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
The urine sampling time points from pre-oral dose through 192 hours post-IV dose were used to assess this outcome.
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
The Feces sampling time points from the 0 hour (i.e. time of oral dose) through 192 hours post-IV dose were used to assess this outcome.
Cmax of LOXO-305
PK: AUC0-t of LOXO 305
AUC0-inf of LOXO-305
Cmax of LOXO-305
PK: AUC0-t of LOXO 305
AUC0-inf of LOXO-305
AUC0-24 of LOXO-305
PK: AUC(0-24) hours of LOXO-305 is reported. AUC(0-24) was calculated by the linear trapezoidal method.
PK: AUC(0-t) of LOXO-305 is reported. AUC(0-t) was calculated by linear trapezoidal method.
PK: AUC(0-inf) of LOXO-305 is reported. AUC(0-inf) was calculated using the formula: AUC(0-inf) = AUC(0-t) + Ct/λZ; where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.
PK: %AUCextrap of LOXO-305 is reported.
PK: Cmax of LOXO-305 is reported.
PK: tmax of LOXO-305 is reported.
PK: t½ of LOXO-305 is reported.
PK: CL/F of LOXO-305 is reported.
| Arm | Type | Description |
|---|---|---|
| LOXO-305 | EXPERIMENTAL | Participants received 200 mg of LOXO-305 administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. |
| Part 1: [14C]-LOXO-305 Oral Solution | EXPERIMENTAL | Participants received a single dose of 200 milligram (mg) LOXO-305 radiolabelled with carbon-14, i.e., \[14C\]-LOXO-305 (approximately 200 microcurie radioactivity) administered as an oral solution. |
| Part 2: LOXO-305 Oral Tablet + [14C]-LOXO-305 IV Solution | EXPERIMENTAL | Participants received: a single dose of 200 mg LOXO-305 administered as 2×100 mg oral tablets followed 2 hours later by a single dose of less than 100 microgram (μg) of \[14C\]-LOXO-305 (approximately 1 microcurie radioactivity) administered as an intravenous (IV) push over approximately 2 minutes. |
| Part 1 (LOXO-305/Itraconazole) | EXPERIMENTAL | * Day 1: a single oral dose of 200 milligrams (mg) LOXO-305 was administered. * Day 8: oral doses of 200 mg itraconazole was administered twice daily. * Days 9 to 18: single oral dose of 200 mg itraconazole was administered once daily, and on Day 12 it was co-administered with a single oral dose of 200 mg LOXO-305. |
| Part 2 (LOXO 305/Rifampin) | EXPERIMENTAL | * Day 1: a single oral dose of 200 mg LOXO-305 was administered. * Days 8 to 23: oral dose of 600 mg rifampin was administered once daily, and on Days 8 \& 17, it was co-administered with a single oral dose of 200 mg LOXO-305. |
| Treatment Sequence 1: ABC | EXPERIMENTAL | * Period 1: Single oral dose of 200 milligram (mg) LOXO-305 (Fasted state) on Day 1 (Treatment A) * Period 2: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 8 (Treatment B) * Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C) A washout period of 7 days was maintained between each treatment period. |
| Treatment Sequence 2: BAC | EXPERIMENTAL | * Period 1: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 1 (Treatment B) * Period 2: Single oral dose of 200 mg LOXO-305 (Fasted state) on Day 8 (Treatment A) * Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C) A washout period of 7 days was maintained between each treatment period. |
| Name | Type | Description |
|---|---|---|
| LOXO-305 | DRUG | Administered orally. |
| [14C]-LOXO-305 | DRUG | Administered orally |
| Itraconazole | DRUG | Oral itraconazole |
| Rifampin | DRUG | Oral rifampin |
| Omeprazole | DRUG | Omeprazole Orally. |
Inclusion Criteria * Participants with histologically confirmed B-cell malignancy including: * Mantle cell lymphoma (MCL) treated with a prior Bruton's tyrosine kinase (BTK) inhibitor containing regimen; * CLL/SLL treated with a prior BTK inhibitor containing regimen; * Other types of B-cell...
LOXO-305 is an investigational small molecule being developed by Eli Lilly and Company (LLY). It is studied in blood cancers including leukemia and lymphoma, as well as in healthy volunteers for drug interaction and metabolism studies. It is currently in clinical development and not approved.
LOXO-305 is being studied for use in blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma, and other B-cell lymphomas. It is also studied in healthy volunteers to assess drug interactions and effects of food and other medications.
LOXO-305 is developed by Eli Lilly and Company, a pharmaceutical company traded on the NYSE under the ticker LLY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various patient populations.
LOXO-305 is in Phase 1 and Phase 2 clinical trials. Completed trials include a Phase 2 study in Chinese participants with blood cancer and Phase 1 studies in healthy volunteers. The drug is investigational and not yet approved by regulatory authorities.
LOXO-305 has completed several trials. NCT04849416 is a Phase 2 study in Chinese participants with blood cancer. NCT05134337 and NCT05134350 are Phase 1 studies in healthy volunteers examining effects of itraconazole, rifampin, food, and omeprazole. NCT06180954 is a Phase 1 study of carbon-14-labeled LOXO-305 in healthy males.
Yes, LOXO-305 is also known as pirtobrutinib. One clinical trial, NCT06180954, explicitly refers to LOXO-305 as pirtobrutinib. This alternative name may be used in scientific literature and other contexts.