Metastatic Cancer
Conditions
Brief summary
This study evaluates the safety and tolerability of different doses of an experimental treatment in participants with advanced cancer.
Interventions
DRUGLY3007113
Administered orally
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 for which available standard therapies have failed to provide clinical benefit for their disease * For Dose Escalation (Part A): cancer, either a solid tumor or a lymphoma * For Dose Confirmation (Part B): cancer, either a solid tumor or a lymphoma * Have the presence of measureable or non-measureable disease (Part A) or measureable disease (Part B) as defined by the Response Evaluation Criteria in Solid Tumors or the Revised Response Criteria for Malignant Lymphoma * Have adequate hematologic, hepatic and renal function * Have a performance status less than or equal to 2 on the Eastern Cooperative Oncology Group scale * Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents * Have an estimated life expectancy of greater than or equal to 12 weeks * Are able to swallow capsules
Exclusion criteria
* Have an echocardiogram with clinically significant abnormalities * For Dose Escalation (Part A): Have central nervous system malignancy or metastasis * For Dose Confirmation (Part B): Have symptomatic central nervous system malignancy or metastasis * Have an acute leukemia * Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and stopped all therapy for that disease for a minimum of 3 years * Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Adverse Events (AEs) (Physical Assessments and Clinical Lab Tests) | Baseline through Study Completion (up to 170 Days) | Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after randomization. A summary of serious AEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Who Achieved a Best Response of Either Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR) | Baseline through Study Completion (up to 170 Days) | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). PR was defined as having at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter without notable worsening of additional tumors that were qualitatively assessed. |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of Single Dose LY3007113 | Cycle 1 Days -3, -2, -1, 1: Predose to 48 hours Postdose | — |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From 0 to Tau (AUC[0-tau]) of Multiple Dose LY3007113 | Cycle 1 Days 28 and 29, Cycle 2 Day 1: Predose to 24 hours Postdose | — |
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Cycle 1 Day -3 (single dose): Predose to 48 hours Postdose; Day 28 (multiple dose): Predose to 24 hours Postdose | — |
Countries
United States
Participant flow
Pre-assignment details
For cohorts 1-3, participants completed the trial if they received at least 75% of planned doses of LY3007113 and completed at least 1 cycle. For Part B, participants completed the trial if they completed at least 2 cycles of study treatment and were assessed for response. (Cycle = 28 days.)
Participants by arm
| Arm | Count |
|---|---|
| 20 mg LY3007113 (Cohort 1) 20 mg LY3007113 administered once orally every 12 hours on Days 1 through 28. (28-day cycle.) Participants may have continued to receive study drug if discontinuation criterion was not met and there was evidence of clinical benefit. | 3 |
| 40 mg LY3007113 (Cohort 2) 40 mg LY3007113 administered once orally every 12 hours on Days 1 through 28. (28-day cycle.) Participants may have continued to receive study drug if discontinuation criterion was not met and there was evidence of clinical benefit. | 4 |
| 30 mg LY3007113 (Cohort 3) 30 mg LY3007113 administered once orally every 12 hours on Days 1 through 28. (28-day cycle.) Participants may have continued to receive study drug if discontinuation criterion was not met and there was evidence of clinical benefit. | 5 |
| 30 mg LY3007113 (Part B) 30 mg LY3007113 administered once orally every 12 hours on Days 1 through 28. (28-day cycle.) Participants may have continued to receive study drug if discontinuation criterion was not met and there was evidence of clinical benefit. | 15 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 20 mg LY3007113 (Cohort 1) | 40 mg LY3007113 (Cohort 2) | 30 mg LY3007113 (Cohort 3) | 30 mg LY3007113 (Part B) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants | 11 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 5 Participants | 13 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 3 Participants | 13 Participants | 22 Participants |
| Region of Enrollment United States | 3 Participants | 4 Participants | 5 Participants | 15 Participants | 27 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 3 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 5 / 5 | 14 / 15 |
| serious Total, serious adverse events | 1 / 3 | 1 / 4 | 2 / 5 | 5 / 15 |
Outcome results
Primary
Number of Participants With Clinically Significant Adverse Events (AEs) (Physical Assessments and Clinical Lab Tests)
Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after randomization. A summary of serious AEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline through Study Completion (up to 170 Days)
Population: Participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 20 mg LY3007113 (Cohort 1) | Number of Participants With Clinically Significant Adverse Events (AEs) (Physical Assessments and Clinical Lab Tests) | 2 Participants |
| 40 mg LY3007113 (Cohort 2) | Number of Participants With Clinically Significant Adverse Events (AEs) (Physical Assessments and Clinical Lab Tests) | 4 Participants |
| 30 mg LY3007113 (Cohort 3) | Number of Participants With Clinically Significant Adverse Events (AEs) (Physical Assessments and Clinical Lab Tests) | 4 Participants |
| 30 mg LY3007113 (Part B) | Number of Participants With Clinically Significant Adverse Events (AEs) (Physical Assessments and Clinical Lab Tests) | 8 Participants |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From 0 to Tau (AUC[0-tau]) of Multiple Dose LY3007113
Time frame: Cycle 1 Days 28 and 29, Cycle 2 Day 1: Predose to 24 hours Postdose
Population: Participants who received at least one dose of study drug and had sufficient evaluable AUC(0-tau) values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg LY3007113 (Cohort 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From 0 to Tau (AUC[0-tau]) of Multiple Dose LY3007113 | 1360 ng*hr/mL | Geometric Coefficient of Variation 23 |
| 40 mg LY3007113 (Cohort 2) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From 0 to Tau (AUC[0-tau]) of Multiple Dose LY3007113 | 3260 ng*hr/mL | Geometric Coefficient of Variation 46 |
| 30 mg LY3007113 (Cohort 3) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From 0 to Tau (AUC[0-tau]) of Multiple Dose LY3007113 | 2070 ng*hr/mL | Geometric Coefficient of Variation 68 |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of Single Dose LY3007113
Time frame: Cycle 1 Days -3, -2, -1, 1: Predose to 48 hours Postdose
Population: Participants who received at least one dose of study drug and had sufficient evaluable AUC(0-inf) values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg LY3007113 (Cohort 1) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of Single Dose LY3007113 | 1560 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| 40 mg LY3007113 (Cohort 2) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of Single Dose LY3007113 | 2480 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
| 30 mg LY3007113 (Cohort 3) | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf]) of Single Dose LY3007113 | 1810 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 67 |
Secondary
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113
Time frame: Cycle 1 Day -3 (single dose): Predose to 48 hours Postdose; Day 28 (multiple dose): Predose to 24 hours Postdose
Population: Participants who received at least one dose of study drug and had sufficient evaluable Cmax values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 20 mg LY3007113 (Cohort 1) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Single dose | 197 ng/mL | Geometric Coefficient of Variation 3 |
| 20 mg LY3007113 (Cohort 1) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Multiple dose | 178 ng/mL | Geometric Coefficient of Variation 31 |
| 40 mg LY3007113 (Cohort 2) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Single dose | 296 ng/mL | Geometric Coefficient of Variation 66 |
| 40 mg LY3007113 (Cohort 2) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Multiple dose | 489 ng/mL | Geometric Coefficient of Variation 31 |
| 30 mg LY3007113 (Cohort 3) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Single dose | 247 ng/mL | Geometric Coefficient of Variation 49 |
| 30 mg LY3007113 (Cohort 3) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY3007113 | Multiple dose | 386 ng/mL | Geometric Coefficient of Variation 64 |
Secondary
The Percentage of Participants Who Achieved a Best Response of Either Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR)
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). PR was defined as having at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter without notable worsening of additional tumors that were qualitatively assessed.
Time frame: Baseline through Study Completion (up to 170 Days)
Population: Participants in Part B who received at least one dose of study drug and were radiologically assessed for tumor response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 20 mg LY3007113 (Cohort 1) | The Percentage of Participants Who Achieved a Best Response of Either Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR) | CR | 0 percentage of participants |
| 20 mg LY3007113 (Cohort 1) | The Percentage of Participants Who Achieved a Best Response of Either Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR) | PR | 0 percentage of participants |