Advanced Cancer
Conditions
Keywords
Advanced cancer, Metastatic cancer, Oncology
Brief summary
The study is to determine the recommended Phase 2 regimen of study drug that may be safely administered to participants with advanced and or metastatic cancer. The study consists of two parts: a dose escalation and a dose confirmation.
Detailed description
Phase 1, first human dose study
Interventions
DRUGFGF Receptor
LY2874455 administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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 (solid tumors, lymphoma, or chronic lymphocytic leukemia) that is advanced and/or metastatic and for which all standard therapies have failed * Have the presence of measurable or non-measurable disease * Have given written informed consent prior to any study-specific procedures * Have adequate organ function including: * Hematologic: Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10(9)/L platelets equal to or greater than 100 x 10(9)/L, and hemoglobin equal to or greater than 8 g/dL. Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin until 14 days after the erythrocyte transfusion * Hepatic: Bilirubin equal to or less than 1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) equal to or less than 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling equal to or less than 5 times ULN are acceptable * Renal: Serum creatinine less than or equal to 1.2 times ULN or calculated creatinine clearance greater than or equal to 60 milliliters per minute using the Standard Cockcroft and Gault Creatinine Clearance Calculation * Calcium and phosphate less than or equal to 1.1 times ULN * Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued chemotherapy and cancer-related hormonal therapy with commercially available agents for at least 21 days (6 weeks for mitomycin-C or nitrosoureas) and radiotherapy for at least 14 days prior to study enrollment and recovered from the acute effects of therapy. Hormone refractory prostate cancer participants receiving gonadotropin releasing hormone (GnRH) agonist therapy or breast cancer participants on antiestrogen therapy (for example, an aromatase inhibitor) prior to entrance on the study may have that treatment continued while they are enrolled in the study * Females with childbearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug. Males and females with reproductive potential must agree to use 2 medically approved contraceptive methods during the trial and for 3 months following the last dose of study drug. Female participants must agree to use 2 medically acceptable methods of contraception, 1 being an oral contraceptive, dermal patch, or progestin (implantation or injection), and the other being a medically acceptable barrier method; alternatively, 2 medically acceptable barrier methods may be used. Medically acceptable barrier methods of contraception that may be used by the participant and/or his/her partner include: abstinence; diaphragm with spermicide; intrauterine device (IUD); condom together with foam, spermicide, or vaginal spermicidal suppository. Prohibited methods include the rhythm method, withdrawal, condoms alone, or diaphragm alone * Have an estimated life expectancy of greater than or equal to 12 weeks
Exclusion criteria
* Have received treatment with an investigational drug, which has not received regulatory approval for any indication, within 28 days of study treatment with LY2874455 * Currently taking agents to control serum phosphate or calcium levels. This includes dietary restrictions * Have medical conditions that, in the opinion of the investigator, would preclude participation in this study * Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastases is not required * Have a history of major organ transplant (for example: heart, lungs, liver, and kidney) * Have current acute leukemia * Females who are pregnant or nursing * An untreated or uncontrolled acute infection, including urinary tract infection, within 7 days of study entry * Have Bazett's corrected QT (QTcB) greater than 470 msec (female) or greater than 450 msec (male), history of unexplained recurrent syncope, history of congenital long QT syndrome, family history of sudden death, or the presence in the screening electrocardiogram (ECG) of a conduction abnormality that in the opinion of the investigator would preclude safe participation in this study * Have had an autologous or allogenic bone marrow transplant * Previously treated with LY2874455
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD) | Baseline Up to 32 Weeks | MTD was determined after the evaluation of Part A portion of the trial. Dose escalation proceeded at 1.3 times the preceding cohort once a Grade 3 non-laboratory toxicity or Grade 2 laboratory toxicity was noted in ≥ 1 participant until MTD was achieved. Doses up to 24 mg (48 mg/day) were evaluated in Part A. The effects at this dose and at 18 mg (36 mg/day) suggested that a reasonable number of participants might not tolerate LY2874455 for chronic administration at these dose levels because of the constellation of effects observed individually or in combination in participants at these dose levels. Therefore, the dose of 16 mg BID of LY2874455 (total dose 32 mg per day) was selected as the initial dose for Part B. Selection of the dose level was based on the tolerability of this dose and without specific toxicities identified. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | Baseline Up to 60 Weeks | Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section. |
| Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | BORR: Baseline Up to 60 Weeks ; ORR: Baseline Up to 60 Weeks | BORR is evaluated using response evaluation criteria in solid tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). Partial Response (PR): 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. Best overall response rate = (unconfirmed CR+ unconfirmed PR) / subjects in efficacy population. Objective response rate = (confirmed CR+ confirmed PR) / subjects in efficacy population. |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Part A and B: Cycle 1, Day 1, Pre-Dose, 0.5 Hr (H), 1 H, 2 H, 4H,8 H,12 H,24 H; Day 28, Pre-Dose, 0.5 H, 1 H, 2 H, 4 H, 8 H | Maximum observed concentration during a dosing interval. |
| Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Part A and B: Cycle 1, Day 1, Pre-Dose, 0.5 Hr (H), 1 H, 2 H, 4H,8 H,12 H,24 H; Day 28, Pre-Dose, 0.5 H, 1 H, 2 H, 4 H, 8 H | Area under the concentration-time curve from time 0 to the end of the dosing interval (e.g., BID) calculated by a combination of linear and logarithmic trapezoidal methods (linear-up/log-down method). |
Countries
Australia, South Korea
Participant flow
Pre-assignment details
A participant was defined as completer of the study after 2 cycles while a participant who discontinued was classified as a discontinuation prior to completing 2 cycles or a discontinuation after 2 cycles. Final disposition for the study is provided.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 2 mg FGF Receptor QD Part A: Dose escalation 2 milligrams (mg) FGF receptor given orally once daily (QD) for a minimum of (1) 28 day cycle. | 3 |
| Part A: 4 mg FGF Receptor QD Part A: Dose escalation 4 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle. | 3 |
| Part A: 10 mg FGF Receptor QD Part A: Dose escalation 10 mg FGF receptor given orally QD for a minimum of (1) 28 day cycle. | 6 |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders Part A: Dose escalation 10 mg FGF receptor + phosphate binders given QD for a minimum of (1) 28 day cycle | 3 |
| Part A: 8 mg FGF Receptor BID Part A: Dose escalation 8 mg of FGF receptor given orally twice a day (BID) for a minimum of (1) 28 day cycle | 3 |
| Part A: 10 mg FGF Receptor BID Part A: Dose escalation 10 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle. | 3 |
| Part A: 14 mg FGF Receptor BID Part A: Dose escalation 14 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle. | 3 |
| Part A: 18 mg FGF Receptor BID Part A: Dose escalation18 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle. | 3 |
| Part A: 24 mg FGF Receptor BID Part A: Dose escalation 24 mg FGF receptor given orally BID for a minimum of (1) 28 day cycle. | 3 |
| Part A: 18 mg FGF Receptor BID Extension Part A: Dose escalation 18 mg FGF Receptor given orally BID for a minimum of (1) 28 day cycle. | 3 |
| Part A: 16 mg FGF Receptor BID Part A: Dose escalation 16 mg FGF Receptor given orally BID for a minimum of (1) 28 day cycle | 3 |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer ) Part B: Dose determined by part a dose escalation 16 mg FGF Receptor given orally BID for a minimum of (1) 28 day cycle | 58 |
| Total | 94 |
Baseline characteristics
| Characteristic | Part A: 2 mg FGF Receptor QD | Total | Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer ) | Part A: 16 mg FGF Receptor BID | Part A: 18 mg FGF Receptor BID Extension | Part A: 24 mg FGF Receptor BID | Part A: 18 mg FGF Receptor BID | Part A: 14 mg FGF Receptor BID | Part A: 10 mg FGF Receptor BID | Part A: 8 mg FGF Receptor BID | Part A: 10 mg FGF Receptor QD + Phosphate Binders | Part A: 10 mg FGF Receptor QD | Part A: 4 mg FGF Receptor QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 15.3 | 57.7 years STANDARD_DEVIATION 11.2 | 58.3 years STANDARD_DEVIATION 9.5 | 62.7 years STANDARD_DEVIATION 14.2 | 52.0 years STANDARD_DEVIATION 24.8 | 55.7 years STANDARD_DEVIATION 6.7 | 44.3 years STANDARD_DEVIATION 3.8 | 56.7 years STANDARD_DEVIATION 13.2 | 52.0 years STANDARD_DEVIATION 11.5 | 65.7 years STANDARD_DEVIATION 9.5 | 63.7 years STANDARD_DEVIATION 10.5 | 57.8 years STANDARD_DEVIATION 18.1 | 59.3 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 94 Participants | 58 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 69 Participants | 52 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 25 Participants | 6 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Australia | 3 Participants | 27 Participants | 7 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants |
| Region of Enrollment South Korea | 0 Participants | 67 Participants | 51 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 30 Participants | 19 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 64 Participants | 39 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 5 Participants | 3 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 58 / 58 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 1 / 6 | 0 / 3 | 2 / 3 | 1 / 3 | 0 / 3 | 2 / 3 | 0 / 3 | 1 / 3 | 1 / 3 | 18 / 58 |
Outcome results
Primary
Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD)
MTD was determined after the evaluation of Part A portion of the trial. Dose escalation proceeded at 1.3 times the preceding cohort once a Grade 3 non-laboratory toxicity or Grade 2 laboratory toxicity was noted in ≥ 1 participant until MTD was achieved. Doses up to 24 mg (48 mg/day) were evaluated in Part A. The effects at this dose and at 18 mg (36 mg/day) suggested that a reasonable number of participants might not tolerate LY2874455 for chronic administration at these dose levels because of the constellation of effects observed individually or in combination in participants at these dose levels. Therefore, the dose of 16 mg BID of LY2874455 (total dose 32 mg per day) was selected as the initial dose for Part B. Selection of the dose level was based on the tolerability of this dose and without specific toxicities identified.
Time frame: Baseline Up to 32 Weeks
Population: All participants who received at least one dose of study drug in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Participants | Recommended Dose for Phase 2 Studies : Maximum Tolerated Dose (MTD) | 16 mg |
Secondary
Number of Participants With Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are events which were not present at baseline or pre-existing conditions at baseline that worsened in severity following the start of treatment. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline Up to 60 Weeks
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Participants | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 4 mg FGF Receptor QD | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 10 mg FGF Receptor QD | Number of Participants With Treatment-Emergent Adverse Events | 6 Participants |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 8 mg FGF Receptor BID | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 10 mg FGF Receptor BID | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 14 mg FGF Receptor BID | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 18 mg FGF Receptor BID | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 24 mg FGF Receptor BID | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 18 mg FGF Receptor BID Extension | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part A: 16 mg FGF Receptor BID | Number of Participants With Treatment-Emergent Adverse Events | 3 Participants |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Number of Participants With Treatment-Emergent Adverse Events | 58 Participants |
Secondary
Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR)
BORR is evaluated using response evaluation criteria in solid tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). Partial Response (PR): 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. Best overall response rate = (unconfirmed CR+ unconfirmed PR) / subjects in efficacy population. Objective response rate = (confirmed CR+ confirmed PR) / subjects in efficacy population.
Time frame: BORR: Baseline Up to 60 Weeks ; ORR: Baseline Up to 60 Weeks
Population: All participants who received at least one dose of study drug and who had CT Scan and progressed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Participants | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A Participants | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 4 mg FGF Receptor QD | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 4 mg FGF Receptor QD | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 10 mg FGF Receptor QD | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 10 mg FGF Receptor QD | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 8 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 8 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 10 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 10 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 14 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 14 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 33.3 percentage of participants |
| Part A: 18 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 18 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 24 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 24 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 18 mg FGF Receptor BID Extension | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part A: 18 mg FGF Receptor BID Extension | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 16 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part A: 16 mg FGF Receptor BID | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 0 percentage of participants |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Objective Response Rate | 0 percentage of participants |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Percentage of Participants With Best Overall Response Rate (BORR) and Objective Response Rate (ORR) | Best Overall Response Rate | 1.9 percentage of participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455
Area under the concentration-time curve from time 0 to the end of the dosing interval (e.g., BID) calculated by a combination of linear and logarithmic trapezoidal methods (linear-up/log-down method).
Time frame: Part A and B: Cycle 1, Day 1, Pre-Dose, 0.5 Hr (H), 1 H, 2 H, 4H,8 H,12 H,24 H; Day 28, Pre-Dose, 0.5 H, 1 H, 2 H, 4 H, 8 H
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Participants | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 32.7 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 62.6 |
| Part A Participants | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 31.1 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 92.1 |
| Part A: 4 mg FGF Receptor QD | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 89.7 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.8 |
| Part A: 4 mg FGF Receptor QD | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 76.9 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 66.7 |
| Part A: 10 mg FGF Receptor QD | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 202 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 13.4 |
| Part A: 10 mg FGF Receptor QD | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 224 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 36.1 |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 421 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 18.1 |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 427 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 11.1 |
| Part A: 8 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 106 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 7.28 |
| Part A: 8 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 229 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 13.2 |
| Part A: 10 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 301 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 38.2 |
| Part A: 10 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 140 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.3 |
| Part A: 14 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 301 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 18.4 |
| Part A: 14 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 566 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 9.83 |
| Part A: 18 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 589 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 24.8 |
| Part A: 18 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 325 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 85.8 |
| Part A: 24 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 500 Hour*nanogram per milliliter (h*ng/mL) | — |
| Part A: 24 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 532 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 33.4 |
| Part A: 18 mg FGF Receptor BID Extension | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 381 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 133 |
| Part A: 18 mg FGF Receptor BID Extension | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 171 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 77.2 |
| Part A: 16 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 291 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 55.8 |
| Part A: 16 mg FGF Receptor BID | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 511 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 64.9 |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 28 | 578 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 47.3 |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Pharmacokinetics (PK): Area Under the Concentration vs Time Curve 0 to Tau ( AUC[0-t]) of LY2874455 | Day 1 | 258 Hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 66 |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455
Maximum observed concentration during a dosing interval.
Time frame: Part A and B: Cycle 1, Day 1, Pre-Dose, 0.5 Hr (H), 1 H, 2 H, 4H,8 H,12 H,24 H; Day 28, Pre-Dose, 0.5 H, 1 H, 2 H, 4 H, 8 H
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Participants | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 6.25 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 59 |
| Part A Participants | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 5.97 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 66.3 |
| Part A: 4 mg FGF Receptor QD | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 8.99 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.1 |
| Part A: 4 mg FGF Receptor QD | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 17.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 55.9 |
| Part A: 10 mg FGF Receptor QD | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 38.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.3 |
| Part A: 10 mg FGF Receptor QD | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 32.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 91.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15.1 |
| Part A: 10 mg FGF Receptor QD + Phosphate Binders | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 36.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 205 |
| Part A: 8 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 43.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15.2 |
| Part A: 8 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 27.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17.1 |
| Part A: 10 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 35.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 52.1 |
| Part A: 10 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 63.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 10.3 |
| Part A: 14 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 58.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12.2 |
| Part A: 14 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 64.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26.9 |
| Part A: 18 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 59.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 76.3 |
| Part A: 18 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 88.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26.7 |
| Part A: 24 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 107 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 19.6 |
| Part A: 24 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 127 nanogram per milliliter (ng/mL) | — |
| Part A: 18 mg FGF Receptor BID Extension | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 29.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 75.6 |
| Part A: 18 mg FGF Receptor BID Extension | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 50.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 167 |
| Part A: 16 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 79.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44.9 |
| Part A: 16 mg FGF Receptor BID | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 63.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 52.2 |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 28 | 99.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.7 |
| Part B: 16 mg FGF Receptor BID (NSCLS & Gastric Cancer) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY2874455 | Day 1 | 57.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 61.7 |