An Open-label Study of GSK1120212 Compared with Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer
Trial overview
Progression-Free Survival (PFS) as assessed by the investigator (INV)
Timeframe: From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)
Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated clinical chemistry parameters: Randomized Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated clinical chemistry parameters: Crossover Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated hematology parameters: Randomized Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated hematology parameters: Crossover Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated clinical chemistry parameters: Randomized Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated clinical chemistry parameters: Crossover Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated hematology parameters: Randomized Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated hematology parameters: Crossover Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
Number of participants with any serious adverse event (SAE) or non-serious adverse event (AE): Randomized Phase
Timeframe: From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months)
Number of participants with any SAE or non-serious AE: Crossover Phase
Timeframe: From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months)
Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
Change from Baseline in SBP and DBP: Crossover Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
Change from Baseline in heart rate: Randomized Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
Change from Baseline in heart rate: Crossover Phase
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
Number of participants with a best response of either a complete response (CR) or partial response (PR) as assessed by the investigator: Randomized Phase
Timeframe: From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months)
Number of participants with a best response of either a CR or PR as assessed by the investigator: Crossover Phase
Timeframe: From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months)
Duration of response (DOR) as assessed by the investigator: Randomized Phase
Timeframe: Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months)
Overall Survival (OS)
Timeframe: Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months)
GSK1120212 plasma pharmacokinetic (PK) concentration
Timeframe: Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose
Participation criteria
- At least 18 years old with histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage IV NSCLC with a positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene.
- Documented tumor progression after receiving at least one, but not more than one, prior approved platinum-containing chemotherapy regimen for advanced stage/metastatic NSCLC.
- History of another malignancy.
- Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures.
- At least 18 years old with histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage IV NSCLC with a positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene. -Documented tumor progression after receiving at least one, but not more than one, prior approved platinum-containing chemotherapy regimen for advanced stage/metastatic NSCLC. -Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. -Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale. -Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. -Life expectancy of at least three months in the opinion of the investigator. -Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization to study treatment and agree to use effective contraception. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the time of randomization to study medication until at least four weeks after the last dose of study treatment. -Adequate baseline organ function.
- History of another malignancy. -Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures. -Treatment with a BRAF or MEK inhibitor or docetaxel as monotherapy or as part of a combination regimen. -Anti-cancer therapy (including chemotherapy and radiation therapy) within the last three weeks. -History or current evidence / risk of retinal vein occlusion or central serous retinopathy. -Any current or history of tumor manifestation in the Central Nervous System. -History or evidence of cardiovascular risk, including QTcB >=480 msec, uncontrolled arrhythmias, acute coronary syndrome, coronary angioplasty, or stenting within 6 months prior to randomization, >=Class II congestive heart failure, treatment refractory hypertension, intra-cardiac defibrillators or permanent pacemakers or cardiac metastases. -Known Human Immunodeficiency Virus, Hepatitis B Virus (HBV), or Hepatitis C Virus (HBC) infection (with the exception of chronic or cleared HBV and HCV infection).
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.