Locally Advanced, Metastatic Solid Tumors
Conditions
Keywords
Tumors, cancer
Brief summary
The purpose of this study is to compare the safety and tolerability of several dose levels of MK-2206 in combination with chemotherapy and targeted therapy agents in participants with locally advanced or metastatic solid tumors. The primary hypotheses are that administration of MK-2206 in combination with either carboplatin + paclitaxel, docetaxel, or erlotinib in participants with locally advanced or metastatic solid tumors will have acceptable tolerability, a dose limiting toxicity (DLT) rate of ≤30%, plasma exposure and pharmacodynamics that exceed target thresholds, and allow for definition of a maximum tolerated dose (MTD) in each of the 3 combinations.
Interventions
DRUGMK-2206
MK-2206 given by mouth (PO) on Days 1, 3, 5, and 7 of each 21-day cycle (30 mg, 45 mg, or 60 mg) OR MK-2206 PO on Day 1 of each 21-day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg)
DRUGdocetaxel
Administered as an IV infusion on Day 1 of each 21-day cycle
DRUGerlotinib
Administered daily (QD) PO in each 21-day cycle
DRUGcarboplatin
Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle
DRUGpaclitaxel
Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle
DRUGcorticosteroid
Administered PO twice a day (BID) on Days 1-3 of each 21-day cycle
Sponsors
Merck Sharp & Dohme LLC
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
: * Participants must have locally advanced or metastatic solid tumors. * Participant is male or female greater than or equal to 18 years of age. * Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale * Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. * Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases. * Participant is able to swallow capsules and has no surgical or anatomical condition that will prevent the Participant from swallowing.
Exclusion criteria
* Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks. * Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration. * Participant is currently participating or has participated in a study with an investigational compound or device within 30 days. * Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Participant with a primary central nervous system tumor. * Participant has known hypersensitivity to the components of study drug. * Participant has a history or current evidence of heart disease. * Participant has evidence of clinically significant bradycardia (slow heart rate). * Participant has uncontrolled high blood pressure. * Participant at significant risk for hypokalemia (low potassium levels). * Participant is a known diabetic * Participant has known psychiatric or substance abuse disorders. * Participant is a user of illicit drugs. * Participant is pregnant or breastfeeding. * Participant is Human Immunodeficiency Virus (HIV) positive. * Participant has known history of Hepatitis B or C or active Hepatitis A. * Participant has symptomatic ascites or pleural effusion. * Participant is receiving treatment with oral corticosteroids. * Participant is using a potent cytochrome P(450) 3A4 (CYP3A4) inhibitor or inducer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | At designated time points on Cycle 1 Day 1 (Up to 48 hours) | Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented. |
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | Cycle 1 (Up to 21 days) | A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented. |
| MTD of MK-2206 Administered Q3W in Combination With Docetaxel | Cycle 1 (up to 21 days) | Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. |
| Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel | Cycle 1 (Up to 21 days) | Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. |
| MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel | Cycle 1 (up to 21 days) | Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. |
| MTD of MK-2206 Administered QOD in Combination With Docetaxel | Cycle 1 (up to 21 days) | Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. |
| MTD of MK-2206 Administered QOD in Combination With Erlotinib | Cycle 1 (up to 21 days) | Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. |
| MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib | Cycle 1 (up to 21 days) | Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. |
| Maximum Plasma Concentration of MK-2206 (Cmax) | At designated time points on Cycle 1 Day 1 (Up to 96 hours) | Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented. |
| Time to Maximum Plasma Concentration of MK-2206 (Tmax) | At designated time points on Cycle 1 Day 1 (Up to 96 hours) | Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented. |
| Minimum Plasma Concentration of MK-2206 (Ctrough) | At designated time points on Cycle 1 Day 1 (Up to 48 hours) | Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | Up to approximately 4 months (6 cycles) | Tumor response was assessed using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and was recorded from the start of the study treatment until the end of treatment. Response categories included: Complete Response (CR): disappearance of all target lesions and Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions. The number of participants who had a tumor response of either CR or PR is presented. |
Participant flow
Recruitment details
77 participants were allocated to one of 3 treatment combinations with MK-2206 according to clinical presentation but 5 participants were not treated due to disease progression before initiation of treatment.
Participants by arm
| Arm | Count |
|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. | 7 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. | 9 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. | 6 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. | 5 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. | 6 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. | 5 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. | 3 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. | 5 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. | 4 |
| MK-2206 45 mg QOD+Erlotinib 100 mg Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle. | 9 |
| MK-2206 45 mg QOD+Erlotinib 150 mg Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle. | 4 |
| MK-2206 135 mg QW+Erlotinib 100 mg Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle. | 6 |
| MK-2206 135 mg QW+Erlotinib 150 mg Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle. | 8 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 2 | 0 | 0 | 1 |
| Overall Study | Progressive disease before treatment | 1 | 5 | 1 | 3 | 4 | 4 | 2 | 1 | 2 | 7 | 3 | 6 | 2 |
| Overall Study | Progressive disease during treatment | 3 | 0 | 3 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Total | MK-2206 135 mg QW+Erlotinib 150 mg | MK-2206 135 mg QW+Erlotinib 100 mg | MK-2206 45 mg QOD+Erlotinib 150 mg | MK-2206 45 mg QOD+Erlotinib 100 mg | MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | MK-2206 60 mg QOD+Carboplatin+Paclitaxel |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.6 Years STANDARD_DEVIATION 15.3 | 56.2 Years STANDARD_DEVIATION 12.4 | 54.1 Years STANDARD_DEVIATION 10.9 | 55.7 Years STANDARD_DEVIATION 12.7 | 61.0 Years STANDARD_DEVIATION 6.4 | 61.6 Years STANDARD_DEVIATION 6.1 | 54.0 Years STANDARD_DEVIATION 9.4 | 57.4 Years STANDARD_DEVIATION 8 | 64.7 Years STANDARD_DEVIATION 12 | 57.4 Years STANDARD_DEVIATION 19.7 | 38.8 Years STANDARD_DEVIATION 12.4 | 63.6 Years STANDARD_DEVIATION 7.8 | 56.2 Years STANDARD_DEVIATION 10.4 | 58.4 Years STANDARD_DEVIATION 13.6 |
| 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 | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 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 | 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 | 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 | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 72 Participants | 8 Participants | 6 Participants | 4 Participants | 8 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 36 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 41 Participants | 4 Participants | 4 Participants | 3 Participants | 7 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 4 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 | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 1 / 9 | 0 / 5 | 0 / 5 | 0 / 6 | 1 / 5 | 0 / 3 | 0 / 4 | 0 / 4 | 1 / 9 | 0 / 4 | 1 / 6 | 1 / 6 |
| other Total, other adverse events | 6 / 6 | 8 / 9 | 5 / 5 | 5 / 5 | 5 / 6 | 5 / 5 | 3 / 3 | 3 / 4 | 4 / 4 | 9 / 9 | 4 / 4 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 8 / 9 | 3 / 5 | 1 / 5 | 2 / 6 | 5 / 5 | 1 / 3 | 3 / 4 | 3 / 4 | 6 / 9 | 1 / 4 | 4 / 6 | 5 / 6 |
Outcome results
Primary
Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented.
Time frame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Population: All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 1630 nmol•hr/L | Standard Deviation 496 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 2700 nmol•hr/L | Standard Deviation 619 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 4130 nmol•hr/L | Standard Deviation 1520 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 7420 nmol•hr/L | Standard Deviation 1250 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 9730 nmol•hr/L | Standard Deviation 2320 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 1320 nmol•hr/L | Standard Deviation 395 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 3000 nmol•hr/L | Standard Deviation 1250 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 8090 nmol•hr/L | Standard Deviation 542 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 7690 nmol•hr/L | Standard Deviation 1550 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 1460 nmol•hr/L | Standard Deviation 417 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 2110 nmol•hr/L | Standard Deviation 637 |
| MK-2206 135 mg QW+Erlotinib 100 mg | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 6420 nmol•hr/L | Standard Deviation 2760 |
| MK-2206 135 mg QW+Erlotinib 150 mg | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) | 6560 nmol•hr/L | Standard Deviation 2650 |
Primary
Maximum Plasma Concentration of MK-2206 (Cmax)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented.
Time frame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Population: All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Maximum Plasma Concentration of MK-2206 (Cmax) | 57.7 nmol/L | Standard Deviation 13.8 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | Maximum Plasma Concentration of MK-2206 (Cmax) | 88.3 nmol/L | Standard Deviation 24.2 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | Maximum Plasma Concentration of MK-2206 (Cmax) | 144 nmol/L | Standard Deviation 57 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | Maximum Plasma Concentration of MK-2206 (Cmax) | 247 nmol/L | Standard Deviation 52.5 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | Maximum Plasma Concentration of MK-2206 (Cmax) | 431 nmol/L | Standard Deviation 249 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | Maximum Plasma Concentration of MK-2206 (Cmax) | 42.9 nmol/L | Standard Deviation 13.3 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | Maximum Plasma Concentration of MK-2206 (Cmax) | 106 nmol/L | Standard Deviation 42.5 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | Maximum Plasma Concentration of MK-2206 (Cmax) | 278 nmol/L | Standard Deviation 35.5 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | Maximum Plasma Concentration of MK-2206 (Cmax) | 287 nmol/L | Standard Deviation 67.6 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | Maximum Plasma Concentration of MK-2206 (Cmax) | 48.8 nmol/L | Standard Deviation 11.2 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | Maximum Plasma Concentration of MK-2206 (Cmax) | 65.6 nmol/L | Standard Deviation 29.3 |
| MK-2206 135 mg QW+Erlotinib 100 mg | Maximum Plasma Concentration of MK-2206 (Cmax) | 212 nmol/L | Standard Deviation 75.9 |
| MK-2206 135 mg QW+Erlotinib 150 mg | Maximum Plasma Concentration of MK-2206 (Cmax) | 244 nmol/L | Standard Deviation 84.2 |
Primary
Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time frame: Cycle 1 (Up to 21 days)
Population: All participants who received MK-2206 QOD+carboplatin+paclitaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel | NA mg |
Primary
Minimum Plasma Concentration of MK-2206 (Ctrough)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration.
Time frame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Population: All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Minimum Plasma Concentration of MK-2206 (Ctrough) | 24.9 nmol/L | Standard Deviation 10.7 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | Minimum Plasma Concentration of MK-2206 (Ctrough) | 40.6 nmol/L | Standard Deviation 11.2 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | Minimum Plasma Concentration of MK-2206 (Ctrough) | 1.36 nmol/L | Standard Deviation 0.898 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | Minimum Plasma Concentration of MK-2206 (Ctrough) | 4.67 nmol/L | Standard Deviation 3.33 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | Minimum Plasma Concentration of MK-2206 (Ctrough) | 2.21 nmol/L | Standard Deviation 1.04 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | Minimum Plasma Concentration of MK-2206 (Ctrough) | 17.1 nmol/L | Standard Deviation 3.66 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | Minimum Plasma Concentration of MK-2206 (Ctrough) | 2.27 nmol/L | Standard Deviation 1.04 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | Minimum Plasma Concentration of MK-2206 (Ctrough) | 3.80 nmol/L | — |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | Minimum Plasma Concentration of MK-2206 (Ctrough) | 3.24 nmol/L | Standard Deviation 0.638 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | Minimum Plasma Concentration of MK-2206 (Ctrough) | 23.8 nmol/L | Standard Deviation 8.12 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | Minimum Plasma Concentration of MK-2206 (Ctrough) | 36.8 nmol/L | Standard Deviation 10.6 |
| MK-2206 135 mg QW+Erlotinib 100 mg | Minimum Plasma Concentration of MK-2206 (Ctrough) | 96.6 nmol/L | Standard Deviation 43.6 |
| MK-2206 135 mg QW+Erlotinib 150 mg | Minimum Plasma Concentration of MK-2206 (Ctrough) | 95.5 nmol/L | Standard Deviation 43.1 |
Primary
MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time frame: Cycle 1 (up to 21 days)
Population: All participants who received MK-2206 Q3W+carboplatin+paclitaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel | NA mg |
Primary
MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time frame: Cycle 1 (up to 21 days)
Population: All participants who received MK-2206 QW+erlotinib and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib | NA mg |
Primary
MTD of MK-2206 Administered Q3W in Combination With Docetaxel
Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time frame: Cycle 1 (up to 21 days)
Population: All participants who received MK-2206 Q3W+docetaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | MTD of MK-2206 Administered Q3W in Combination With Docetaxel | NA mg |
Primary
MTD of MK-2206 Administered QOD in Combination With Docetaxel
Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time frame: Cycle 1 (up to 21 days)
Population: All participants who received MK-2206 QOD+docetaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | MTD of MK-2206 Administered QOD in Combination With Docetaxel | NA mg |
Primary
MTD of MK-2206 Administered QOD in Combination With Erlotinib
Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time frame: Cycle 1 (up to 21 days)
Population: All participants who received MK-2206 QOD+erlotinib and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | MTD of MK-2206 Administered QOD in Combination With Erlotinib | NA mg |
Primary
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented.
Time frame: Cycle 1 (Up to 21 days)
Population: All participants that have received one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 2 Participants |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 2 Participants |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 3 Participants |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
| MK-2206 45 mg QOD+Erlotinib 100 mg | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 2 Participants |
| MK-2206 45 mg QOD+Erlotinib 150 mg | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
| MK-2206 135 mg QW+Erlotinib 100 mg | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| MK-2206 135 mg QW+Erlotinib 150 mg | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
Primary
Time to Maximum Plasma Concentration of MK-2206 (Tmax)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented.
Time frame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Population: All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 4.0 hours |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 8.0 hours |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 6.0 hours |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 10.0 hours |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 5.0 hours |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 6.0 hours |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 4.0 hours |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 6.0 hours |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 6.0 hours |
| MK-2206 45 mg QOD+Erlotinib 100 mg | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 6.0 hours |
| MK-2206 45 mg QOD+Erlotinib 150 mg | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 7.0 hours |
| MK-2206 135 mg QW+Erlotinib 100 mg | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 6.0 hours |
| MK-2206 135 mg QW+Erlotinib 150 mg | Time to Maximum Plasma Concentration of MK-2206 (Tmax) | 4.0 hours |
Secondary
Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
Tumor response was assessed using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and was recorded from the start of the study treatment until the end of treatment. Response categories included: Complete Response (CR): disappearance of all target lesions and Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions. The number of participants who had a tumor response of either CR or PR is presented.
Time frame: Up to approximately 4 months (6 cycles)
Population: All participants who received at least one dose of study treatment and had measurable disease at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 1 Participants |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 3 Participants |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 1 Participants |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 1 Participants |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 45 mg QOD+Erlotinib 100 mg | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 45 mg QOD+Erlotinib 150 mg | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 135 mg QW+Erlotinib 100 mg | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |
| MK-2206 135 mg QW+Erlotinib 150 mg | Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) | 0 Participants |