Advanced Cancer
Conditions
Keywords
Cancer, Terminal, Solid Tumor, End Stage, Metastatic
Brief summary
The purpose of this study is to find a recommended dose level and schedule of dosing LY2940680 that can safely be taken by participants with advanced cancer. The study will also explore the changes in a cancer marker level in skin, hair follicles, buccal cells, and tumor cells. Finally, the study will help document any antitumor activity this drug may have.
Detailed description
Participants may include those who have previously received treatment with another hedgehog smoothened (Hh/Smo) inhibitor (excluding LY2940680).
Interventions
DRUGTaladegib
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy. * Have the presence of measurable or nonmeasurable disease * Have adequate organ function, including: * Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, and hemoglobin greater than or equal to 9 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin until 5 days after the erythrocyte transfusion. * Hepatic: Bilirubin less than or equal to 1.5 times upper limits of normal (ULN), ALT, and aspartate transferase (AST) less than or equal to 2.0 times ULN. If the liver has tumor involvement AST and ALT equaling less than or equal to 5 times ULN are acceptable. * Renal: Serum creatinine less than or equal to 1.5 times ULN. * Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued previous treatments for cancer and recovered from the acute effects of therapy (for example, at least 42 days for mitomycin-C or nitrosoureas, 28 days for other chemotherapy and biologics. At the discretion of the investigator, hormone refractory prostate cancer patients who are stable on gonadotropin-releasing hormone (GnRH) agonist therapy and breast cancer patients who are stable on antiestrogen therapy (for example, an aromatase inhibitor) may continue treatment
Exclusion criteria
* Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication. * Have serious preexisting medical conditions * Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days. * Have known current hematologic malignancies or acute or chronic leukemia * Have a known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis (screening is not required) * Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results * Have QTc interval of \>500 msec on screening electrocardiogram * Patients who have previously received treatment with LY2940680
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose: Maximum Tolerated Dose | Time to First Dose to the End of Cycle 1 of Part A (Up To 28 Days) | Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest tested dose that had \<33% probability of causing a DLT in Cycle 1 of Part A. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h | PK: Maximum Observed Drug Concentration (Cmax) |
| PK: Time of Maximal Concentration (Tmax) | Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h | PK: Time of Maximal Concentration (Tmax) |
| PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h | PK: Area Under the Plasma Concentration-time Curve from time Zero to 24 Hours (AUC\[0-24\]) of LSN3185556 |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h | Pharmacokinetics (PK): 1.Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC\[0-∞\]) |
| PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h | PK: Time of Maximal Concentration (Tmax) |
| Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | Baseline to Disease Progression or Death Due to Any Cause (Up To 32 Months) | Clinical Benefit Rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions. |
| Part C and D: Progression Free Survival (PFS) | Baseline to Progressive Disease or Death from Any Cause (Up To 32 Months) | For each participant in Part C and D who is not known to have died or to have had a progression of disease as of the data inclusion cut-off date, PFS was censored at the date of last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Progressive disease (PD) was determined using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
| PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 |
Countries
United States
Participant flow
Pre-assignment details
Study completers are participants who received at least one dose of study drug and were evaluated for safety. Part B of the study was not implemented as the estimated half-life was considered long enough for once a day (QD) dosing.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Cohort 1 Part A Cohort 1: 50 milligram (mg) taladegib administered orally QD on a 28-day cycle. | 3 |
| Part A: Cohort 2 Part A Cohort 2 : 100 mg taladegib administered orally QD on a 28-day cycle. | 6 |
| Part A: Cohort 3 Part A Cohort 3: 200 mg taladegib administered orally QD on a 28-day cycle. | 3 |
| Part A: Cohort 4 Part A Cohort 4: 400 mg taladegib administered orally QD on a 28-day cycle. | 6 |
| Part A: Cohort 5 Part A Cohort 5: 600 mg taladegib administered orally QD on a 28-day cycle. | 7 |
| Part C Part C: 400 mg taladegib administered orally QD. Participants with advanced solid tumors. | 19 |
| Part D Part D: 400 mg taladegib administered orally QD. Participants with advanced basal cell carcinoma (BCC). | 40 |
| Total | 84 |
Baseline characteristics
| Characteristic | Part A: Cohort 1 | Total | Part D | Part C | Part A: Cohort 5 | Part A: Cohort 4 | Part A: Cohort 3 | Part A: Cohort 2 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 14.57 | 63.1 years STANDARD_DEVIATION 11.92 | 64.0 years STANDARD_DEVIATION 12.47 | 62.5 years STANDARD_DEVIATION 10.59 | 65.6 years STANDARD_DEVIATION 11.34 | 60.7 years STANDARD_DEVIATION 14.05 | 67.3 years STANDARD_DEVIATION 7.37 | 57.2 years STANDARD_DEVIATION 14.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 80 Participants | 38 Participants | 18 Participants | 7 Participants | 6 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 79 Participants | 36 Participants | 18 Participants | 7 Participants | 6 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 3 Participants | 84 Participants | 40 Participants | 19 Participants | 7 Participants | 6 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 23 Participants | 8 Participants | 6 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 61 Participants | 32 Participants | 13 Participants | 5 Participants | 3 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 3 / 3 | 6 / 6 | 7 / 7 | 19 / 19 | 40 / 40 |
| serious Total, serious adverse events | 0 / 3 | 3 / 6 | 0 / 3 | 3 / 6 | 1 / 7 | 4 / 19 | 10 / 40 |
Outcome results
Primary
Recommended Phase 2 Dose: Maximum Tolerated Dose
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest tested dose that had \<33% probability of causing a DLT in Cycle 1 of Part A.
Time frame: Time to First Dose to the End of Cycle 1 of Part A (Up To 28 Days)
Population: Part A participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Part A Participants | Recommended Phase 2 Dose: Maximum Tolerated Dose | 400 milligrams (mg) |
Secondary
Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR])
Clinical Benefit Rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions.
Time frame: Baseline to Disease Progression or Death Due to Any Cause (Up To 32 Months)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Part A Participants | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 2 Participants |
| 100 mg Taladegib | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 1 Participants |
| 200 mg Taladegib | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 2 Participants |
| 400 mg Taladegib | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 1 Participants |
| 600 mg Taladegib | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 2 Participants |
| Part C | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 4 Participants |
| Part D | Number of Participants With Clinical Benefit Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]) | 37 Participants |
Secondary
Part C and D: Progression Free Survival (PFS)
For each participant in Part C and D who is not known to have died or to have had a progression of disease as of the data inclusion cut-off date, PFS was censored at the date of last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Progressive disease (PD) was determined using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: Baseline to Progressive Disease or Death from Any Cause (Up To 32 Months)
Population: Part C and Part D participants who received at least one dose of study drug and had evaluable PFS data. Participants censored were Part C=8 and Part D=22. Per protocol, Part A data were not collected for PFS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Part A Participants | Part C and D: Progression Free Survival (PFS) | 1.74 months |
| 100 mg Taladegib | Part C and D: Progression Free Survival (PFS) | 9.07 months |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])
Pharmacokinetics (PK): 1.Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC\[0-∞\])
Time frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h
Population: All participants who received at least one dose of study drug and had evaluable PK data. All participants who received 400 mg taladegib were analyzed together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Part A Participants | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 1 | NA nanogram*hour/milliliter (μg*h/mL) | — |
| All Part A Participants | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 15 | NA nanogram*hour/milliliter (μg*h/mL) | — |
| 100 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 1 | 8.70 nanogram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 101 |
| 100 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 15 | 12.4 nanogram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 113 |
| 200 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 1 | NA nanogram*hour/milliliter (μg*h/mL) | — |
| 200 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 15 | NA nanogram*hour/milliliter (μg*h/mL) | — |
| 400 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 15 | 93.8 nanogram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 103 |
| 400 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 1 | 53.7 nanogram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 99.1 |
| 600 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 1 | 96.2 nanogram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 74.8 |
| 600 mg Taladegib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Cycle 1, Day 15 | NA nanogram*hour/milliliter (μg*h/mL) | — |
Secondary
PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556
PK: Area Under the Plasma Concentration-time Curve from time Zero to 24 Hours (AUC\[0-24\]) of LSN3185556
Time frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h
Population: All participants who received at least one dose of study drug and had evaluable PK data. All participants who received 400 mg taladegib were analyzed together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Part A Participants | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 1 | NA microgram*hour/milliliter (μg*h/mL) | — |
| All Part A Participants | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 15 | NA microgram*hour/milliliter (μg*h/mL) | — |
| 100 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 1 | 7.91 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 50.1 |
| 100 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 15 | 22.9 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 67.6 |
| 200 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 1 | NA microgram*hour/milliliter (μg*h/mL) | — |
| 200 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 15 | NA microgram*hour/milliliter (μg*h/mL) | — |
| 400 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 15 | 121 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 81 |
| 400 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 1 | 36.6 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 70.1 |
| 600 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 1 | 67.4 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 67.7 |
| 600 mg Taladegib | PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of LSN3185556 | Cycle 1, Day 15 | NA microgram*hour/milliliter (μg*h/mL) | — |
Secondary
PK: Maximum Observed Drug Concentration (Cmax)
PK: Maximum Observed Drug Concentration (Cmax)
Time frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h
Population: All participants who received at least one dose of study drug and had evaluable PK data. All participants who received 400 mg taladegib were analyzed together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Part A Participants | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 1 | NA microgram per milliliter (μg/mL) | — |
| All Part A Participants | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 15 | NA microgram per milliliter (μg/mL) | — |
| 100 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 1 | 0.45 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 59.87 |
| 100 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 15 | 0.71 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 71.67 |
| 200 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 1 | 1.29 microgram per milliliter (μg/mL) | — |
| 200 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 15 | NA microgram per milliliter (μg/mL) | — |
| 400 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 15 | 3.62 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 59 |
| 400 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 1 | 2.07 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 66.39 |
| 600 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 1 | 3.28 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 34.36 |
| 600 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) | Cycle 1, Day 15 | NA microgram per milliliter (μg/mL) | — |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556
PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556
Time frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h
Population: All participants who received at least one dose of study drug and had evaluable PK data. All participants who received 400 mg taladegib were analyzed together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Part A Participants | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 15 | NA microgram per milliliter (μg/mL) | — |
| All Part A Participants | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 1 | NA microgram per milliliter (μg/mL) | — |
| 100 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 15 | 1.53 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 60.18 |
| 100 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 1 | 0.51 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 37.28 |
| 200 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 1 | NA microgram per milliliter (μg/mL) | — |
| 200 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 15 | NA microgram per milliliter (μg/mL) | — |
| 400 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 1 | 2.27 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 62.82 |
| 400 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 15 | 7.18 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 72.2 |
| 600 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 15 | NA microgram per milliliter (μg/mL) | — |
| 600 mg Taladegib | PK: Maximum Observed Drug Concentration (Cmax) of LSN3185556 | Cycle 1, Day 1 | 4.18 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 73.72 |
Secondary
PK: Time of Maximal Concentration (Tmax)
PK: Time of Maximal Concentration (Tmax)
Time frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h
Population: All participants who received at least one dose of study drug and had evaluable PK data. All participants who received 400 mg taladegib were analyzed together.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Part A Participants | PK: Time of Maximal Concentration (Tmax) | Cycle 1, Day 1 | 2.03 hour (h) |
| All Part A Participants | PK: Time of Maximal Concentration (Tmax) | Cycle 1,Day 15 | 2.0 hour (h) |
| 100 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1, Day 1 | 3.92 hour (h) |
| 100 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1,Day 15 | 4.10 hour (h) |
| 200 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1, Day 1 | 1.22 hour (h) |
| 200 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1,Day 15 | 1.00 hour (h) |
| 400 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1,Day 15 | 2.00 hour (h) |
| 400 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1, Day 1 | 2.00 hour (h) |
| 600 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1, Day 1 | 3.82 hour (h) |
| 600 mg Taladegib | PK: Time of Maximal Concentration (Tmax) | Cycle 1,Day 15 | 4.08 hour (h) |
Secondary
PK: Time of Maximal Concentration (Tmax) of LSN3185556
PK: Time of Maximal Concentration (Tmax)
Time frame: Cycle 1, Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 hour(h), Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10,11, 12 h
Population: All participants who received at least one dose of study drug and had evaluable PK data. All participants who received 400 mg taladegib were analyzed together.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Part A Participants | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1, Day 1 | 24.25 hour (h) |
| All Part A Participants | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1,Day 15 | 8.00 hour (h) |
| 100 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1, Day 1 | 16.81 hour (h) |
| 100 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1,Day 15 | 8.99 hour (h) |
| 200 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1, Day 1 | 6.00 hour (h) |
| 200 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1,Day 15 | 8.00 hour (h) |
| 400 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1,Day 15 | 1.74 hour (h) |
| 400 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1, Day 1 | 22.67 hour (h) |
| 600 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1, Day 1 | 24.00 hour (h) |
| 600 mg Taladegib | PK: Time of Maximal Concentration (Tmax) of LSN3185556 | Cycle 1,Day 15 | 8.00 hour (h) |