Advanced/Metastatic Solid Tumors
Conditions
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
Brief summary
This study will examine the safety, pharmacokinetics, and efficacy of escalating doses of selumetinib (MK-5618) in combination with intravenous (IV) pembrolizumab (MK-3475) for participants with advanced / metastatic solid tumors.
Interventions
DRUGSelumetinib
Selumetinib oral capsules administered BID at escalating dose levels. Selumetinib administered only in weeks 1&2 of each 3-week treatment cycle.
DRUGPembrolizumab
Pembrolizumab administered by IV infusion at 200 mg Q3W, given on cycle day 1 of each 3-week treatment cycle.
Sponsors
Merck Sharp & Dohme LLC
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
* Has a histologically or cytologically confirmed advanced or metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit. * Has measurable disease by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by local site investigator/radiology. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Is able to swallow and retain oral medication and has no clinically significant gastrointestinal abnormalities that might alter absorption. * Has adequate organ function. * If male, agree to use a contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. * If female, is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP). If a WOCBP, agree to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention. * For Human immunodeficiency virus (HIV) infected participants, must have well controlled HIV on a stable regimen of anti-retroviral therapy (ART). Participants on ART must have been without changes in drugs or dose modification for at least 4 weeks prior to study entry.
Exclusion criteria
* Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study treatment, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related AEs). Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study. * Has clinically active central nervous system metastases and/or carcinomatous meningitis. * Has had a severe hypersensitivity reaction (≥ Grade 3) to treatment with a monoclonal antibody/component of the study treatment, and/or has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents and/or excipients used in the study. * Has an active infection requiring therapy. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment and is allowed. Use of non-systemic steroids is permitted. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to allocation. * Has known Hepatitis B or C infection. * For HIV infected participants, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Has undergone major surgery and has not recovered adequately from any toxicity and/or complications from the intervention prior to starting study therapy. * Has baseline peripheral neuropathy/paresthesia Grade 1. * Has any medical, psychiatric, cognitive, or other condition that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol, or complete the study, in the opinion of the treating investigator. * Participants with clinically significant cardiovascular disease as defined by the following: 1) Uncontrolled hypertension; 2) Left ventricular ejection fraction (LVEF) \<55%; 3) Symptomatic heart failure (New York Heart Association (NYHA) Grade II to IV), prior or current cardiomyopathy, or severe valvular heart disease; 4) Uncontrolled angina; 5) Clinically significant cardiac arrhythmia and/or conduction abnormality ≤6 months prior to start of study treatment; 6) Myocardial infarction or acute coronary syndrome ≤6 months prior to start of study treatment; 7) Mean QT interval calculated according to the Frederica method (QTcF) interval: Male \>450 ms; Female \>470 ms. * Has a history of thromboembolic or cerebrovascular event(s) within 6 months prior to study enrollment, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism. * Has a neuromuscular disorder associated with an elevated creatine kinase (e.g., inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy. * Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes). * Has retinal degenerative disease. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study treatments hazardous or make it difficult to monitor adverse effects such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator. * Has a known psychiatric or substance abuse disorder that would interfere with the Participant's ability to cooperate with the requirements of the study. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. * Has received a live-virus vaccine within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. * Is currently participating and receiving study treatment in a study of an investigational agent or has participated and received study treatment in a study of an investigational agent or has used an investigational device within 28 days of administration of selumetinib. * Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | Up to 21 days | DLT was defined as toxicities that: 1) were possibly, probably, or definitely related to study therapy, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma; and 2) met pre-defined severity criteria. For each arm, the number of participants experiencing DLTs were assessed. |
| Number of Participants Who Experienced Adverse Event (AE) | Up to ~28 months | An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed. |
| Number of Participants Discontinuing Study Treatment Due to an Adverse Event | Up to ~28 months | An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated withthe use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC) of Selumetinib. | Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14. | Plasma selumetinib concentration was quantified for each arm to determine AUC, defined as the area under the concentration-time curve for selumetinib. AUC(0-last) is area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration. AUC (0-12) is area under the concentration-time curve from dosing (time 0) to 12 hours. |
| Maximum Observed Plasma Concentration (Cmax) of Selumetinib | Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14. | Plasma selumetinib concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of selumetinib in plasma. |
| Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14. | Plasma selumetinib concentration was quantified for each arm to determine Cmin, defined as the minimum observed concentration of selumetinib in plasma. |
Countries
Canada, United States
Participant flow
Recruitment details
Though the total planned enrollment for this study was 50 participants. Only 32 participants were allocated and included in Part 1, dose escalation for analysis. Part 2 cohort expansion was not initiated. The study was terminated after completion of dose escalation due to reasons unrelated to safety or tolerability.
Participants by arm
| Arm | Count |
|---|---|
| Selumetinib 50mg + Pembrolizumab Participants received 200 mg pembrolizumab (IV infusion; every three weeks \[Q3W\]) in combination with selumetinib 50mg orally twice daily \[BID\]) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib was administered only for the first two weeks. | 4 |
| Selumetinib 75mg + Pembrolizumab Participants received 200 mg pembrolizumab (IV infusion; every three weeks \[Q3W\]) in combination with selumetinib 75mg orally twice daily \[BID\]) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib was administered only for the first two weeks. | 3 |
| Selumetinib 100mg + Pembrolizumab Participants received 200 mg pembrolizumab (IV infusion; every three weeks \[Q3W\]) in combination with selumetinib 100mg orally twice daily \[BID\]) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib was administered only for the first two weeks. | 11 |
| Selumetinib 125mg + Pembrolizumab Participants received 200 mg pembrolizumab (IV infusion; every three weeks \[Q3W\]) in combination with selumetinib 125mg orally twice daily \[BID\]) for up to 35 treatment cycles (cycle length: 3 weeks). During each 3-week cycle, selumetinib was administered only for the first two weeks. | 14 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 2 | 9 | 11 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 1 | 3 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Selumetinib 125mg + Pembrolizumab | Selumetinib 100mg + Pembrolizumab | Selumetinib 75mg + Pembrolizumab | Selumetinib 50mg + Pembrolizumab |
|---|---|---|---|---|---|
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 64 years | 29 Participants | 12 Participants | 10 Participants | 3 Participants | 4 Participants |
| Age, Customized From 65 to 84 years | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 10 Participants | 11 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 11 Participants | 9 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 10 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 22 Participants | 11 Participants | 7 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 2 / 3 | 10 / 11 | 11 / 14 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 11 / 11 | 14 / 14 |
| serious Total, serious adverse events | 2 / 4 | 2 / 3 | 4 / 11 | 4 / 14 |
Outcome results
Primary
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated withthe use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE was assessed.
Time frame: Up to ~28 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selumetinib 50mg + Pembrolizumab | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 0 Participants |
| Selumetinib 75mg + Pembrolizumab | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 1 Participants |
| Selumetinib 100mg + Pembrolizumab | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 4 Participants |
| Selumetinib 125mg + Pembrolizumab | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 3 Participants |
Primary
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLT was defined as toxicities that: 1) were possibly, probably, or definitely related to study therapy, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma; and 2) met pre-defined severity criteria. For each arm, the number of participants experiencing DLTs were assessed.
Time frame: Up to 21 days
Population: All allocated participants who received at least one dose of study treatment and met the protocol-specified criteria for DLT evaluability.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selumetinib 50mg + Pembrolizumab | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Selumetinib 75mg + Pembrolizumab | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Selumetinib 100mg + Pembrolizumab | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Selumetinib 125mg + Pembrolizumab | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 3 Participants |
Primary
Number of Participants Who Experienced Adverse Event (AE)
An AE was any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.
Time frame: Up to ~28 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selumetinib 50mg + Pembrolizumab | Number of Participants Who Experienced Adverse Event (AE) | 4 Participants |
| Selumetinib 75mg + Pembrolizumab | Number of Participants Who Experienced Adverse Event (AE) | 3 Participants |
| Selumetinib 100mg + Pembrolizumab | Number of Participants Who Experienced Adverse Event (AE) | 11 Participants |
| Selumetinib 125mg + Pembrolizumab | Number of Participants Who Experienced Adverse Event (AE) | 14 Participants |
Secondary
Area Under the Concentration-Time Curve (AUC) of Selumetinib.
Plasma selumetinib concentration was quantified for each arm to determine AUC, defined as the area under the concentration-time curve for selumetinib. AUC(0-last) is area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration. AUC (0-12) is area under the concentration-time curve from dosing (time 0) to 12 hours.
Time frame: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.
Population: All allocated participants who were compliant with the study procedures and had AUC data available from at least 1 treatment dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Selumetinib 50mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-last | 2080 hr*ng/mL | Geometric Coefficient of Variation 71.4 |
| Selumetinib 50mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-12 | 2160 hr*ng/mL | Geometric Coefficient of Variation 73.1 |
| Selumetinib 75mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-12 | 4220 hr*ng/mL | Geometric Coefficient of Variation 8.5 |
| Selumetinib 75mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-last | 3800 hr*ng/mL | Geometric Coefficient of Variation 5.7 |
| Selumetinib 100mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-last | 4660 hr*ng/mL | Geometric Coefficient of Variation 51.2 |
| Selumetinib 100mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-12 | 5060 hr*ng/mL | Geometric Coefficient of Variation 47.7 |
| Selumetinib 125mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-last | 4430 hr*ng/mL | Geometric Coefficient of Variation 57.6 |
| Selumetinib 125mg + Pembrolizumab | Area Under the Concentration-Time Curve (AUC) of Selumetinib. | AUC0-12 | 4760 hr*ng/mL | Geometric Coefficient of Variation 62 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Selumetinib
Plasma selumetinib concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of selumetinib in plasma.
Time frame: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.
Population: All allocated participants who were compliant with the study procedures and had Cmax data available from at least 1 treatment dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Selumetinib 50mg + Pembrolizumab | Maximum Observed Plasma Concentration (Cmax) of Selumetinib | 852 ng/mL | Geometric Coefficient of Variation 79.5 |
| Selumetinib 75mg + Pembrolizumab | Maximum Observed Plasma Concentration (Cmax) of Selumetinib | 1400 ng/mL | Geometric Coefficient of Variation 33.4 |
| Selumetinib 100mg + Pembrolizumab | Maximum Observed Plasma Concentration (Cmax) of Selumetinib | 1690 ng/mL | Geometric Coefficient of Variation 90.4 |
| Selumetinib 125mg + Pembrolizumab | Maximum Observed Plasma Concentration (Cmax) of Selumetinib | 1410 ng/mL | Geometric Coefficient of Variation 70.5 |
Secondary
Minimum Observed Plasma Concentration (Cmin) of Selumetinib
Plasma selumetinib concentration was quantified for each arm to determine Cmin, defined as the minimum observed concentration of selumetinib in plasma.
Time frame: Pre-dose, 1, 2, 4, 6, between 8 and 12 hours post dose on Day 1; Time 0 pre-dose at Cycle 2 Day 1, Cycle 2 Day 14, Cycle 5 Day 1 and Cycle 5 Day 14.
Population: All allocated participants who were compliant with the study procedures and had Cmin data available from at least 1 treatment dose at each time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Selumetinib 50mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib-Cycle 2 Day 1 | NA %GCV | — |
| Selumetinib 50mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 2 Day 14 | 72.5 %GCV | Geometric Coefficient of Variation 54.4 |
| Selumetinib 50mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 1 | NA %GCV | — |
| Selumetinib 50mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 14 | 67.8 %GCV | — |
| Selumetinib 75mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 2 Day 14 | 218 %GCV | — |
| Selumetinib 75mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 1 | NA %GCV | — |
| Selumetinib 75mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 14 | NA %GCV | — |
| Selumetinib 75mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib-Cycle 2 Day 1 | NA %GCV | — |
| Selumetinib 100mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 1 | NA %GCV | — |
| Selumetinib 100mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 2 Day 14 | 225 %GCV | Geometric Coefficient of Variation 82.6 |
| Selumetinib 100mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 14 | 529 %GCV | Geometric Coefficient of Variation 98.3 |
| Selumetinib 100mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib-Cycle 2 Day 1 | NA %GCV | — |
| Selumetinib 125mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 14 | 175 %GCV | Geometric Coefficient of Variation 192.7 |
| Selumetinib 125mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 2 Day 14 | 283 %GCV | Geometric Coefficient of Variation 123.2 |
| Selumetinib 125mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib-Cycle 2 Day 1 | 2.05 %GCV | Geometric Coefficient of Variation 313.1 |
| Selumetinib 125mg + Pembrolizumab | Minimum Observed Plasma Concentration (Cmin) of Selumetinib | Selumetinib- Cycle 5 Day 1 | NA %GCV | — |