Carcinoma, Non-small Cell Lung, Metastases, Neoplasm, Neuroendocrine Tumors, Renal Cell Carcinoma
Conditions
Keywords
Advanced Cancer, Metastatic Cancer, Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Neuroendocrine Tumors
Brief summary
Study I3G-MC-JGCB (JGCB) is a multicenter, nonrandomized, open-label, dose-escalation Phase 1b study of LY2584702 in combination with either erlotinib or everolimus.
Detailed description
Study JGCB will consist of the following parts: Part 1 - Dose Escalation to maximum tolerated dose in each arm. Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic cancer. Arm B - LY2584702 + Everolimus in participants with advanced or metastatic cancer. Part 2 - Dose Confirmation of maximum tolerated dose from each arm in Part 1. Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic non-small cell lung cancer. Arm B - LY2584702 + Everolimus in participants with advanced renal cell carcinoma after treatment failure with sunitinib or sorafenib, or advanced neuroendocrine tumors.
Interventions
DRUGLY2584702
Supplied as 25 milligrams (mg) and 100 mg capsules, administered orally for two 28-day cycles.
DRUGErlotinib
Supplied as 25 mg, 100 mg, or 150 mg tablets, administered orally, daily for two 28-day cycles. Starting dose is 150mg. Doses may be decreased in 50mg increments if necessary due to toxicity.
DRUGEverolimus
Supplied as 5 mg or 10 mg tablets, administered orally, daily for two 28-day cycles.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) for which no proven effective therapy exists. * Dose Confirmation portion (Part 2): have histological or cytological evidence of: 1. Arm A: advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. 2. Arm B: advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib, or advanced neuroendocrine tumors. * Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma. 1. Dose Escalation portion (Part 1): participants may have measurable or nonmeasurable disease. 2. Dose Confirmation portion (Part 2): participants must have measurable disease. * Have adequate organ function including: 1. Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10⁹/liters (L), platelets greater than or equal to 100 x 10⁹/L, and hemoglobin greater than or equal to 8 grams/deciliter (g/dL). 2. Hepatic: bilirubin less than or equal to 1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling less than or equal to 5 times ULN are acceptable. Participants with bone metastases may enter with alkaline phosphatase values less than or equal to 5 times ULN, as long as other hepatic parameters meet inclusion criteria. 3. Renal: Serum creatinine less than or equal to 1.5 times ULN or calculated creatinine clearance \>45 milliliter/minute (ml/mn). * Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrollment, and have recovered from the acute effects of therapy. At the discretion of the investigator, participants with prostate cancers progressing under luteinizing hormone-releasing hormone (LHRH) agonists therapy, and participants with adrenal carcinomas using mitotane, may have that treatment continued while receiving study drug.
Exclusion criteria
* Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively. * Have serious preexisting 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 and asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required. * Concomitant treatment by strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers. * Have an acute or chronic leukemia. * Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogeneic stem-cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease. * For Dose Confirmation portion (Part 2): have previously received erlotinib for Arm A or everolimus for Arm B.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose for Phase 2 Studies | Baseline up to 6 cycles of 28 days | The recommended dose for the Phase 2 (Dose Confirmation Phase) study was determined by safety assessment. Doses were escalated following the assessment for toxicity based on Common Terminology Criteria for Adverse Events (CTCAE v4.0). Any adverse events (AE) that were possibly related to LY2584702 were considered toxicities. The Phase 2 dose of LY2584702 was not determined due to unacceptable toxicities of LY2584702 in combination with erlotinib or everolimus in Phase 1 of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Effects (Number of Participants With Adverse Events) | Baseline up to 7 months | Clinically significant events were defined as serious adverse events (SAEs) and other non-SAEs regardless of causality. A summary of serious and other non SAEs regardless of causality is located in the Reported Adverse Event module. |
| Progression-Free Survival (PFS) | Baseline to disease progression or death or up to 166 days postbaseline | PFS was defined as the time from the date of enrollment to the date of objectively determined progressive disease (PD) or death whichever comes first. Censoring of PFS was defined as participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective assessment; for participants who received subsequent systematic anticancer therapy (after discontinuation from study treatment) prior to objectively determined disease progression, PFS was censored at the date of the last objective progression-free disease assessment prior to post discontinuation of therapy. PFS was not analyzed due to different tumor types and different doses. |
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | Baseline to disease progression or death or up to 6 cycles of 28 days | Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions. |
| Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | Cycle 1 Days 1 (C1 D1) and Cycle 1 Day 8 (C1 D8) of 28-day cycle | AUC from time 0 to 8 hours (AUC0-8) and AUC from time 0 to infinity (AUC0-∞). |
| Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | Baseline up to 112 Days | BOR was determined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of LD of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria. |
| Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | Cycle 1 Day 1 (C1 D1): predose, 0.5, 1, 2, 3, 5, 8 hours postdose and Cycle 1 Day 8 (C1 D8): predose, 0.5, 1, 2, 3, 5, and 8 hours postdose of 28-day cycle | — |
Other
| Measure | Time frame |
|---|---|
| Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | Within 30 days of study drug discontinuation |
Countries
France, United States
Participant flow
Pre-assignment details
A 2 phase study, a dose escalation phase and a dose confirmation phase. The dose confirmation phase was not initiated. Participant flow reports those participants who discontinued from study drug. Participants who completed 1 cycle of treatment, had the required assessment or an adverse event (AE) were considered to have completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Arm A - 50 mg LY2584702 QD + 150 mg Erlotinib QD 50 milligrams (mg) LY2584702 administered orally once daily (QD) plus 150 mg erlotinib administered orally QD for two 28-day cycles. | 4 |
| Arm A - 50 mg LY2584702 BID + 150 mg Erlotinib QD 50 mg LY2584702 administered orally twice daily (BID) plus 150 mg erlotinib administered orally QD for two 28-day cycles. | 5 |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD 100 mg LY2584702 administered orally BID plus 150 mg erlotinib administered orally QD for two 28-day cycles. | 3 |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD 75 mg LY2584702 administered orally BID plus 150 mg erlotinib administered orally QD for two 28-day cycles. | 5 |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD 50 mg LY2584702 administered orally QD plus 10 mg everolimus administered orally QD for two 28-day cycles. | 3 |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD 100 mg LY2584702 administered orally QD plus 10 mg everolimus administered orally QD for two 28-day cycles. | 3 |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD 50 mg LY2584702 administered orally BID plus 10 mg everolimus administered orally QD for two 28-day cycles. | 6 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease during Cycle1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm A - 50 mg LY2584702 QD + 150 mg Erlotinib QD | Total | Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Arm A - 50 mg LY2584702 BID + 150 mg Erlotinib QD |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 7.97 | 54.0 years STANDARD_DEVIATION 11.65 | 47.5 years STANDARD_DEVIATION 16.17 | 47.7 years STANDARD_DEVIATION 16.01 | 49.0 years STANDARD_DEVIATION 7.55 | 63.0 years STANDARD_DEVIATION 3.39 | 52.3 years STANDARD_DEVIATION 11.02 | 61.4 years STANDARD_DEVIATION 7.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 26 Participants | 5 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 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 |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 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 | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 24 Participants | 4 Participants | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 3 Participants |
| Region of Enrollment France | 4 Participants | 25 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 0 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 3 Participants | 15 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 14 Participants | 3 Participants | 1 Participants | 1 Participants | 4 Participants | 1 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 3 / 3 | 5 / 5 | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 1 / 4 | 2 / 5 | 2 / 3 | 3 / 5 | 2 / 3 | 2 / 3 | 2 / 6 |
Outcome results
Primary
Recommended Dose for Phase 2 Studies
The recommended dose for the Phase 2 (Dose Confirmation Phase) study was determined by safety assessment. Doses were escalated following the assessment for toxicity based on Common Terminology Criteria for Adverse Events (CTCAE v4.0). Any adverse events (AE) that were possibly related to LY2584702 were considered toxicities. The Phase 2 dose of LY2584702 was not determined due to unacceptable toxicities of LY2584702 in combination with erlotinib or everolimus in Phase 1 of the study.
Time frame: Baseline up to 6 cycles of 28 days
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2584702 + Erlotinib | Recommended Dose for Phase 2 Studies | NA milligrams (mg) |
| LY2584702+Everolimus | Recommended Dose for Phase 2 Studies | NA milligrams (mg) |
Secondary
Clinically Significant Effects (Number of Participants With Adverse Events)
Clinically significant events were defined as serious adverse events (SAEs) and other non-SAEs regardless of causality. A summary of serious and other non SAEs regardless of causality is located in the Reported Adverse Event module.
Time frame: Baseline up to 7 months
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY2584702 + Erlotinib | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 4 Participants |
| LY2584702 + Erlotinib | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 1 Participants |
| LY2584702+Everolimus | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 2 Participants |
| LY2584702+Everolimus | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 5 Participants |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 3 Participants |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 2 Participants |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 3 Participants |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 5 Participants |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 3 Participants |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 2 Participants |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 2 Participants |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 3 Participants |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Clinically Significant Effects (Number of Participants With Adverse Events) | Non-SAEs | 6 Participants |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Clinically Significant Effects (Number of Participants With Adverse Events) | SAEs | 2 Participants |
Secondary
Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)]
BOR was determined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of LD of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria.
Time frame: Baseline up to 112 Days
Population: All participants who received at least 1 dose of study drug and assessed for BOR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LY2584702 + Erlotinib | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 1 Participants |
| LY2584702+Everolimus | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 1 Participants |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 1 Participants |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 1 Participants |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 0 Participants |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 2 Participants |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)] | 2 Participants |
Secondary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)]
Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions.
Time frame: Baseline to disease progression or death or up to 6 cycles of 28 days
Population: All participants who received at least 1 dose of study drug and assessed for RR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2584702 + Erlotinib | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
| LY2584702+Everolimus | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)] | 0 percentage of participants |
Secondary
Pharmacokinetics, Area Under the Concentration Time Curve (AUC)
AUC from time 0 to 8 hours (AUC0-8) and AUC from time 0 to infinity (AUC0-∞).
Time frame: Cycle 1 Days 1 (C1 D1) and Cycle 1 Day 8 (C1 D8) of 28-day cycle
Population: All participants who received at least 1 dose of study drug and had AUC values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2584702 + Erlotinib | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 8699.54 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 38 |
| LY2584702 + Erlotinib | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 5395.96 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 70.7 |
| LY2584702 + Erlotinib | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 4436.60 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50.6 |
| LY2584702+Everolimus | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 7948.43 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50.4 |
| LY2584702+Everolimus | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 4308.98 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 79.8 |
| LY2584702+Everolimus | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 7627.50 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 37.9 |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 20813.83 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 8610.54 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 49.4 |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 15225.08 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 16254.07 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20.3 |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 8091.93 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 47.8 |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 13959.74 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 45.6 |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 5460.80 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 23.3 |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 5699.856 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 31.9 |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 11386.03 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 34.8 |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 11327.33 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 34.7 |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 11410.18 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 3.9 |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 22343.07 nanograms*hours per milliliter (ng*h/mL) | — |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-∞, D1, single dose | 8764.13 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 14.1 |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D8, steady state | 10527.68 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 44.1 |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Pharmacokinetics, Area Under the Concentration Time Curve (AUC) | AUC0-8, D1, single dose | 6097.44 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 15.9 |
Secondary
Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702
Time frame: Cycle 1 Day 1 (C1 D1): predose, 0.5, 1, 2, 3, 5, 8 hours postdose and Cycle 1 Day 8 (C1 D8): predose, 0.5, 1, 2, 3, 5, and 8 hours postdose of 28-day cycle
Population: All participants who received at least 1 dose of study drug and had Cmax values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2584702 + Erlotinib | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 918.24 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.9 |
| LY2584702 + Erlotinib | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 1125.46 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.6 |
| LY2584702+Everolimus | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 999.54 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68.3 |
| LY2584702+Everolimus | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 1636.71 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.6 |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 2421.64 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.1 |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 2709.61 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.7 |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 1768.59 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.3 |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 1967.04 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.8 |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 1192.46 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.5 |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 1169.95 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.2 |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 2286.22 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 7.3 |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 2260.71 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.8 |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D1, single dose | 1569.24 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.6 |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702 | C1 D8, steady state | 2109.62 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.1 |
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time from the date of enrollment to the date of objectively determined progressive disease (PD) or death whichever comes first. Censoring of PFS was defined as participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective assessment; for participants who received subsequent systematic anticancer therapy (after discontinuation from study treatment) prior to objectively determined disease progression, PFS was censored at the date of the last objective progression-free disease assessment prior to post discontinuation of therapy. PFS was not analyzed due to different tumor types and different doses.
Time frame: Baseline to disease progression or death or up to 166 days postbaseline
Population: Zero participants were analyzed as no data collected.
Other Pre-specified
Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation
Time frame: Within 30 days of study drug discontinuation
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LY2584702 + Erlotinib | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 0 Participants |
| LY2584702+Everolimus | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 0 Participants |
| Arm A - 100 mg LY2584702 BID + 150 mg Erlotinib QD | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 0 Participants |
| Arm A - 75 mg LY2584702 BID + 150 mg Erlotinib QD | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 0 Participants |
| Arm B - 50 mg LY2584702 QD + 10 mg Everolimus QD | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 1 Participants |
| Arm B - 100 mg LY2584702 QD + 10 mg Everolimus QD | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 0 Participants |
| Arm B - 50 mg LY2584702 BID + 10 mg Everolimus QD | Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation | 0 Participants |