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A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung
Phase 1 trial testing Binimetinib in Lungcancer in 13 participants. Completed in 4 July 2019.
| Lead sponsor | University Health Network, Toronto |
|---|---|
| Phase | Phase 1 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | na |
| Design | single group |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 13 |
| Start date | 7 March 2017 |
| Primary completion | 4 July 2019 |
| Estimated completion | 4 July 2019 |
| Sites | 4 locations across Canada |
University Health Network, Toronto
Adults 18 to 90, any sex, with Lungcancer. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
To determine the recommended dose in milligrams per day of the combination of MEK162 with standard therapy pemetrexed and carboplatin as determined by toxicity.
| Group | Value | 95% CI |
|---|---|---|
| Binimetinib Dose Level 1 & 2 (30mg BID & 45mg BID) | 30 |
The size of tumors in centimeters before and after treatment. The measurements will be compared against the RECIST v1.1 criteria to ascertain response as defined in the protocol. Objective response rate (ORR) was defined as the percentage of patients who achieved a complete or partial response as the best overall response.
| Group | Value | 95% CI |
|---|---|---|
| Binimetinib Dose Level 1 (30mg BID) | 4 | |
| Binimetinib Dose Level 2 (45mg BID) | 2 |
Exploratory analysis of mutation subtypes using next generation sequencing (NGS).
| Group | Value | 95% CI |
|---|---|---|
| KRAS/NRAS-mutated Patients | 62.5 | |
| KRAS/NRAS Wild-type Patients | 25 |
Evaluation progression-free survival rate (PFS) for patients with and without KRAS mutation in tumor tissue. PFS is defined as the time from start of treatment to disease progression or death. PFS rate is measured over 6 months period (26 weeks). PFS rate is calculated as a percentage of participants achieving a 6 months (26 weeks) period of progression free survival.
| Group | Value | 95% CI |
|---|---|---|
| Overall Study Progression Free Survival Rate | 38.5 | 19.3 – 76.5 |
Time frame: Adverse events (AE) were recorded for 22 weeks of treatment.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Binimetinib Dose Level 1 (… | Binimetinib Dose Level 2 (… | Binimetinib Dose Level -1 … |
|---|---|---|---|---|
| Diverticulitis (grade 3) | Gastrointestinal disorders | — | — | — |
| Febrile neutropenia (grade 3) | Immune system disorders | — | — | — |
| Pulmonary infection (grade 2) | Respiratory, thoracic and mediastinal disorders | — | — | — |
| Anemia (grade 3) | Blood and lymphatic system disorders | — | — | — |
| Confusion | Nervous system disorders | — | — | — |
| Cerebral metastases | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — | — | — |
| Reaction | System | Binimetinib Dose Level 1 (… | Binimetinib Dose Level 2 (… | Binimetinib Dose Level -1 … |
|---|---|---|---|---|
| Dry skin/Rash | Skin and subcutaneous tissue disorders | — | — | — |
| Ocular toxicity | Eye disorders | — | — | — |
| Diarrhea | Gastrointestinal disorders | — | — | — |
| Fatigue | General disorders | — | — | — |
| Mucositis (Oral, Nasal) | Gastrointestinal disorders | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — |
| Edema | General disorders | — | — | — |
| Anemia | Blood and lymphatic system disorders | — | — | — |
| Joint Pain | Musculoskeletal and connective tissue disorders | — | — | — |
| Neutrophil Count Decrease | Immune system disorders | — | — | — |
| ALT Increase | Hepatobiliary disorders | — | — | — |
| AST Increase | Hepatobiliary disorders | — | — | — |
| Anorexia | Gastrointestinal disorders | — | — | — |
| Bilateral Leg Weakness | Musculoskeletal and connective tissue disorders | — | — | — |
| Bilirubin Increase | Hepatobiliary disorders | — | — | — |
| Dysuria/Hematuria | Renal and urinary disorders | — | — | — |
| Ejection Fraction Decrease | Cardiac disorders | — | — | — |
| Epistaxis | Blood and lymphatic system disorders | — | — | — |
| Hypokalemia | Metabolism and nutrition disorders | — | — | — |
| Palpitations/Sinus tachycardia | Cardiac disorders | — | — | — |
| Paronychia | Infections and infestations | — | — | — |
| Serum Amylase Increase | Hepatobiliary disorders | — | — | — |
| Vertigo | Nervous system disorders | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — |
| Weight Gain | Metabolism and nutrition disorders | — | — | — |
| Weight Loss | Metabolism and nutrition disorders | — | — | — |
| White Blood Cell Decrease | Immune system disorders | — | — | — |
Most-reported serious reactions: Diverticulitis (grade 3), Febrile neutropenia (grade 3), Pulmonary infection (grade 2), Anemia (grade 3), Confusion, Cerebral metastases.
Data from ClinicalTrials.gov NCT02185690 adverse events section.
MEK162 has shown significant inhibition of tumor growth as a single agent in NSCLC xenograft models in mice and human cancer cells in vitro, which have KRAS and/or other mutations. These data suggest that MEK162 may provide a potential benefit in cancer indications harboring these mutations. MEK162 is currently being investigated in phase I clinical testing and has been well tolerated up to an MTD of 45mg BID in cancer patients. There has been little change in survival benefit for patients with non-small cell lung cancer in recent years. Emerging new treatment options relying on molecular and genetic markers are being studied extensively. Thus, there has been a shift to manage non-small cell lung cancer with molecular targeted therapies in combination with standard chemotherapy. This study will be targeting patients with KRAS mutations.
7 peer-reviewed publications reference this trial (live from Europe PMC):
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