Neoplasm Metastasis, Neoplasms
Conditions
Brief summary
The main purpose of this study is to evaluate the safety of a study drug known as LY3164530 in participants with cancer that is advanced and/or has spread to another part(s) of the body.
Interventions
DRUGLY3164530
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 advanced or metastatic cancer and be an appropriate candidate for experimental therapy. * Have adequate organ function. * Prior Treatments: * Systemic treatments: Must have discontinued previous systemic treatments for cancer and recovered from the acute effects of therapy. Participants must have discontinued: * Cytotoxic therapies or targeted agents that are small molecule inhibitors for 5 half-lives or at least 28 days. * Mitomycin-C or nitrosourea therapy for at least 42 days and biologic agents for at least 28 days. * Radiation therapy and surgery must be completed 4 weeks prior to therapy, except for limited field radiation therapy, which must be completed 2 weeks before therapy. * If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for three months following the last dose of study drug. * If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 14 days of the first dose of study drug and must not be breast feeding.
Exclusion criteria
* Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment. * Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C. * Must not have a serious preexisting medical conditions or concomitant disorders. * Must not have leukemia. * Must not have QT interval of \>470 millisecond. * Must not have a serious cardiac condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose of LY3164530: Maximum Tolerated Dose (MTD) | Cycle 1 (Cycle = 28 days) | Recommended Phase 2 Dose of LY3164530: MTD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1) | Cmax in Schedule (Sched) 1 Cycle 1 (C1) and Cycle 2 (C2) and Sched. 2 C1 and C2 dose escalation based on EGFR specific ELISA assay. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion. |
| Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1) | Cmax in Schedule 1 Cycles 1 and 2 and Schedule 2 Cycles 1 and 2 based on the MET-specific ELISA assay. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion. |
| Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1) | Area under the serum concentration-time curve of LY3164530 over the dosing interval (AUC\[0-τ\]) from time 0 to 336 hours (τ) \[Schedule 1\] or from time 0-168 hours (τ) \[Schedule 2\]. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion. |
| Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1) | Area under the serum concentration-time curve of LY3164530 over the dosing interval (AUC\[0-τ\]) from time 0 to 336 hours (τ) \[Schedule 1\] or from time 0-168 hours (τ) \[Schedule 2\]. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion. |
| Number of Participants With Tumor Response | Baseline Through Study Completion (Up to 6 Months) | Number of Participants with Tumor Response |
Countries
United States
Participant flow
Pre-assignment details
Participants, who completed at least 1 cycle of treatment or discontinued due to an adverse event during Cycle 1 and completed the required post-treatment safety assessment, were considered to have completed the study.
Participants by arm
| Arm | Count |
|---|---|
| 300 mg LY3164530 Schedule 1 300 mg LY3164530 given intravenously (IV) on Days 1 and 15 of each 28 day cycle. | 3 |
| 600 mg LY3164530 Schedule 1 600 mg LY3164530 given IV on Days 1, and 15 of each 28 day cycle. | 3 |
| 1000 mg LY3164530 Schedule 1 1000 mg LY3164530 given IV on Days 1 and 15 of each 28 day cycle. | 11 |
| 1250 mg LY3164530 Schedule 1 1250 mg LY3164530 given IV on Days 1 and 15 of each 28 day cycle. | 3 |
| 500 mg LY3164530 Schedule 2 500 mg LY3164530 given IV on Days 1, 8, 15, and 22 of each 28 day cycle. | 5 |
| 600 mg LY3164530 Schedule 2 600 mg LY3164530 given IV on Days 1, 8, 15, and 22 of each 28 day cycle. | 4 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 4 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | 600 mg LY3164530 Schedule 1 | 1000 mg LY3164530 Schedule 1 | 1250 mg LY3164530 Schedule 1 | 300 mg LY3164530 Schedule 1 | 500 mg LY3164530 Schedule 2 | 600 mg LY3164530 Schedule 2 |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 1 Participants | 8 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 3 Participants | 11 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants |
| Region of Enrollment United States | 29 Participants | 3 Participants | 11 Participants | 3 Participants | 3 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 12 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 17 Participants | 3 Participants | 8 Participants | 1 Participants | 1 Participants | 3 Participants | 1 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 0 / 11 | 0 / 3 | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 11 / 11 | 3 / 3 | 5 / 5 | 4 / 4 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 3 / 11 | 0 / 3 | 0 / 5 | 0 / 4 |
Outcome results
Primary
Recommended Phase 2 Dose of LY3164530: Maximum Tolerated Dose (MTD)
Recommended Phase 2 Dose of LY3164530: MTD
Time frame: Cycle 1 (Cycle = 28 days)
Population: All participants who receive at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Schedule 1 | Recommended Phase 2 Dose of LY3164530: Maximum Tolerated Dose (MTD) | 1000 milligrams (mg) |
| Schedule 2 | Recommended Phase 2 Dose of LY3164530: Maximum Tolerated Dose (MTD) | 500 milligrams (mg) |
Secondary
Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay
Area under the serum concentration-time curve of LY3164530 over the dosing interval (AUC\[0-τ\]) from time 0 to 336 hours (τ) \[Schedule 1\] or from time 0-168 hours (τ) \[Schedule 2\]. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion.
Time frame: Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | NA micrograms*milliliter per hour(µg*mL/hr) | — |
| Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 5580 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 28 |
| Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 6690 micrograms*milliliter per hour(µg*mL/hr) | — |
| Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 13700 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 15 |
| Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 9870 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 23 |
| Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA micrograms*milliliter per hour(µg*mL/hr) | — |
| 1000 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 42700 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 39 |
| 1000 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 37000 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 42 |
| 1000 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 43000 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 55 |
| 1250 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 81400 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 31 |
| 1250 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 57500 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 28 |
| 1250 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 51500 micrograms*milliliter per hour(µg*mL/hr) | — |
| 500 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 25500 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 35 |
| 500 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 16700 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 37 |
| 500 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 26300 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 35 |
| 600 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 19800 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 21 |
| 600 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA micrograms*milliliter per hour(µg*mL/hr) | — |
| 600 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 EGFR Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 34900 micrograms*milliliter per hour(µg*mL/hr) | Geometric Coefficient of Variation 31 |
Secondary
Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay
Area under the serum concentration-time curve of LY3164530 over the dosing interval (AUC\[0-τ\]) from time 0 to 336 hours (τ) \[Schedule 1\] or from time 0-168 hours (τ) \[Schedule 2\]. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion.
Time frame: Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | NA µg*hr/mL | — |
| Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 6150 µg*hr/mL | Geometric Coefficient of Variation 26 |
| Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 6800 µg*hr/mL | — |
| Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 12900 µg*hr/mL | Geometric Coefficient of Variation 14 |
| Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 10900 µg*hr/mL | Geometric Coefficient of Variation 27 |
| Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA µg*hr/mL | — |
| 1000 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 43000 µg*hr/mL | Geometric Coefficient of Variation 34 |
| 1000 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 37500 µg*hr/mL | Geometric Coefficient of Variation 41 |
| 1000 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 44700 µg*hr/mL | Geometric Coefficient of Variation 45 |
| 1250 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 82000 µg*hr/mL | Geometric Coefficient of Variation 33 |
| 1250 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 57300 µg*hr/mL | Geometric Coefficient of Variation 31 |
| 1250 mg LY3164530 Schedule 1 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 46400 µg*hr/mL | — |
| 500 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 24800 µg*hr/mL | Geometric Coefficient of Variation 29 |
| 500 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 16300 µg*hr/mL | Geometric Coefficient of Variation 22 |
| 500 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 24800 µg*hr/mL | Geometric Coefficient of Variation 34 |
| 600 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 17500 µg*hr/mL | Geometric Coefficient of Variation 20 |
| 600 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA µg*hr/mL | — |
| 600 mg LY3164530 Schedule 2 | Area Under the Serum Concentration-Time Curve (AUC[0-τ]) of LY3164530 MET Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1 Day 2 | 31200 µg*hr/mL | Geometric Coefficient of Variation 30 |
Secondary
Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay
Cmax in Schedule (Sched) 1 Cycle 1 (C1) and Cycle 2 (C2) and Sched. 2 C1 and C2 dose escalation based on EGFR specific ELISA assay. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion.
Time frame: Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | NA microgram per milliliter (µg/mL ) | — |
| Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 85.1 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 38 |
| Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 72.19 microgram per milliliter (µg/mL ) | — |
| Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 147 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 15 |
| Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 122 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 12 |
| Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA microgram per milliliter (µg/mL ) | — |
| 1000 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 348 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 34 |
| 1000 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 367 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 52 |
| 1000 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 357 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 35 |
| 1250 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 615 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 38 |
| 1250 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 496 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 30 |
| 1250 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 468.9 microgram per milliliter (µg/mL ) | — |
| 500 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 262 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 35 |
| 500 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 226 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 20 |
| 500 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 270 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 32 |
| 600 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 255 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 21 |
| 600 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA microgram per milliliter (µg/mL ) | — |
| 600 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Epidermal Growth Factor Receptor (EGFR) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 350 microgram per milliliter (µg/mL ) | Geometric Coefficient of Variation 20 |
Secondary
Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay
Cmax in Schedule 1 Cycles 1 and 2 and Schedule 2 Cycles 1 and 2 based on the MET-specific ELISA assay. Pharmacokinetic (PK) Time Frame Schedule 1:Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2 hours (hrs), 4hrs, 6hrs, 24 ±4hrs post-infusion; Day 3: anytime during day; Day 8 ±1 : anytime during day. Day 15: Pre-dose, End of infusion; 2hrs, 4hrs, 6hrs post-infusion; Day 22 ±2: anytime during day. Cycles 3-6: Pre-dose, End of infusion. PK Time Frame: Schedule 2: Cycle 1 and 2 (Day 1): Predose; Mid-infusion; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 3: anytime during day; Day 8: Pre-dose; End of infusion; Day 22: Pre-dose; End of infusion; 2hrs, 4hrs, 6hrs, 24 ±4hrs post-infusion (Cycle 1); Day 24: anytime during day. Cycles 3-6: Pre-dose; End of Infusion.
Time frame: Cycle 1 predose (Day 1) up to Cycle 6 end of infusion (Day 1)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | NA µg/mL | — |
| Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 82.5 µg/mL | Geometric Coefficient of Variation 41 |
| Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 72.32 µg/mL | — |
| Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 136 µg/mL | Geometric Coefficient of Variation 12 |
| Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 124 µg/mL | Geometric Coefficient of Variation 15 |
| Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA µg/mL | — |
| 1000 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 346 µg/mL | Geometric Coefficient of Variation 33 |
| 1000 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 365 µg/mL | Geometric Coefficient of Variation 46 |
| 1000 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 353 µg/mL | Geometric Coefficient of Variation 27 |
| 1250 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 587 µg/mL | Geometric Coefficient of Variation 35 |
| 1250 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 498 µg/mL | Geometric Coefficient of Variation 33 |
| 1250 mg LY3164530 Schedule 1 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 400.9 µg/mL | — |
| 500 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 260 µg/mL | Geometric Coefficient of Variation 32 |
| 500 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 208 µg/mL | Geometric Coefficient of Variation 23 |
| 500 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | 258 µg/mL | Geometric Coefficient of Variation 27 |
| 600 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 1; Schedule 2 Cycle 1 Day 1 | 221 µg/mL | Geometric Coefficient of Variation 21 |
| 600 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 2 Day 1; Schedule 2 Cycle 2 Day 1 | NA µg/mL | — |
| 600 mg LY3164530 Schedule 2 | Maximum Serum Concentration (Cmax) of LY3164530 Mesenchymal-Epithelial Transition Factor (MET) Specific ELISA Assay | Schedule 1 Cycle 1 Day 15;Schedule 2 Cycle 1Day 22 | 317 µg/mL | Geometric Coefficient of Variation 17 |
Secondary
Number of Participants With Tumor Response
Number of Participants with Tumor Response
Time frame: Baseline Through Study Completion (Up to 6 Months)
Population: All participants who received at least one dose of study drug and had at least one post-baseline tumor assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Schedule 1 | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| Schedule 1 | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| Schedule 1 | Number of Participants With Tumor Response | Stable Disease | 1 Participants |
| Schedule 1 | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| Schedule 2 | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| Schedule 2 | Number of Participants With Tumor Response | Stable Disease | 1 Participants |
| Schedule 2 | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| Schedule 2 | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 1000 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Stable Disease | 6 Participants |
| 1000 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 1000 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 1000 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Progressive Disease | 3 Participants |
| 1250 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 1250 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 1250 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Stable Disease | 1 Participants |
| 1250 mg LY3164530 Schedule 1 | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| 500 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| 500 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Partial Response | 2 Participants |
| 500 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 500 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Stable Disease | 1 Participants |
| 600 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Partial Response | 1 Participants |
| 600 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Stable Disease | 2 Participants |
| 600 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Progressive Disease | 1 Participants |
| 600 mg LY3164530 Schedule 2 | Number of Participants With Tumor Response | Complete Response | 0 Participants |