The purpose of this study is to determine the safety of an extracellular signal regulated kinase (ERK1/2) inhibitor LY3214996 administered alone or in combination with other agents in participants with advanced cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
210
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Florida Cancer Specialists
Sarasota, Florida, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs)
Time frame: Cycle 1 (21 Days)
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of LY3214996 Administered as Monotherapy and when Administered in Combination with Nab-Paclitaxel Plus Gemcitabine, Abemaciclib and Encorafenib Plus Cetuximab
Time frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles)
PK: AUC of Gemcitabine when Administered with LY3214996
Time frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
PK: AUC of Nab-Paclitaxel when Administered with LY3214996
Time frame: Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
PK: AUC of Abemaciclib and its Metabolites when Administered with LY3214996
Time frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
PK: AUC of Encorafenib when Administered with LY3214996
Time frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
PK: AUC of Cetuximab when Administered with LY3214996
Time frame: Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
PK: AUC of Midazolam and its 1'-Hydroxymidazolam Metabolite when Administered Alone and in Combination with LY3214996
Time frame: Cycle 1 Day 1 through Cycle 1 Day 16 (21 Day Cycles)
Objective Response Rate (ORR): Percentage of Participants With a Complete (CR) or Partial Response (PR)
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Administered IV
Administered IV
Administered orally
Administered IV
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Sarah Cannon Cancer Center
Nashville, Tennessee, United States
Tennessee Oncology PLLC
Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
St Vincent's Hospital
Sydney, New South Wales, Australia
Linear Clinical Research Ltd
Nedlands, Western Australia, Australia
...and 3 more locations
Time frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 6 Months)
Duration of Response (DoR)
Time frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 12 Months)
Time to First Response (TTR)
Time frame: Baseline to Date of CR or PR (Estimated up to 6 Months)
Progression Free Survival (PFS)
Time frame: Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months)
Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR
Time frame: Baseline through Measured Progressive Disease (Estimated up to 6 Months)
Overall Survival (OS) (Dose Expansion Arms Only)
Time frame: Baseline to Date of Death from Any Cause (Estimated up to 2 Years)