Primary Outcome Measures: | |
1. |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Assessed up to 6 months from time of first dose ]
Incidence and severity of treatment-emergent AEs and serious AEs |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Assessed up to 6 months from time of first dose ]
Incidence and severity of treatment-emergent AEs and serious AEs |
2. |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Assessed up to 6 months from time of first dose ]
Objective response rate (ORR) based on assessment of radiographic imaging RECIST v1.1 |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Assessed up to 6 months from time of first dose ]
Objective response rate (ORR) based on assessment of radiographic imaging RECIST v1.1 |
3. |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Study Day 1 up to Day 29 ]
Maximum plasma concentration of ERAS-254 and trametinib |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Study Day 1 up to Day 29 ]
Maximum plasma concentration of ERAS-254 and trametinib |
4. |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Study Day 1 up to Day 29 ]
Time to achieve maximum plasma concentration of ERAS-254 and trametinib |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Study Day 1 up to Day 29 ]
Time to achieve maximum plasma concentration of ERAS-254 and trametinib |
5. |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Study Day 1 up to Day 29 ]
Area under the plasma concentration-time curve |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 [ Time Frame: Study Day 1 up to Day 29 ]
Area under the plasma concentration-time curve |
6. |
Stage 2: To compare PFS and OS for patients who are randomized to receive the combination of naporafenib + trametinib to that of patients who receive physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) [ Time Frame: Assessed up to 24 months from time of first dose ]
- Progression free survival (PFS) based on assessment of radiographic imaging per RECIST v1.1
- Survival status
|
Stage 2: To compare PFS and OS for patients who are randomized to receive the combination of naporafenib + trametinib to that of patients who receive physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) [ Time Frame: Assessed up to 24 months from time of first dose ]
- Progression free survival (PFS) based on assessment of radiographic imaging per RECIST v1.1
- Survival status
|
Secondary Outcome Measures: | |
1. |
Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
Incidence and severity of treatment-emergent AEs and serious AEs |
Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
Incidence and severity of treatment-emergent AEs and serious AEs |
2. |
Duration of Response (DOR) [ Time Frame: Assessed up to 24 months from time of first dose] ]
Based on assessment of radiographic imaging per RECIST version 1.1 |
Duration of Response (DOR) [ Time Frame: Assessed up to 24 months from time of first dose] ]
Based on assessment of radiographic imaging per RECIST version 1.1 |
3. |
Time to Response (TTR) [ Time Frame: Assessed up to 24 months from time of first dose] ]
Based on assessment of radiographic imaging per RECIST version 1.1 |
Time to Response (TTR) [ Time Frame: Assessed up to 24 months from time of first dose] ]
Based on assessment of radiographic imaging per RECIST version 1.1 |
4. |
Disease Control Rate (DCR) [ Time Frame: Assessed up to 24 months from time of first dose] ]
Based on assessment of radiographic imaging per RECIST version 1.1 |
Disease Control Rate (DCR) [ Time Frame: Assessed up to 24 months from time of first dose] ]
Based on assessment of radiographic imaging per RECIST version 1.1 |
5. |
Overall Response Rate (ORR) [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on the assessment of radiographic imaging per RECIST version 1.1 |
Overall Response Rate (ORR) [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on the assessment of radiographic imaging per RECIST version 1.1 |
6. |
Plasma concentration (Cmax):Stage 1 only [ Time Frame: Study Day 1 up to Day 29 ]
Maximum plasma concentration of ERAS-254 and trametinib |
Plasma concentration (Cmax):Stage 1 only [ Time Frame: Study Day 1 up to Day 29 ]
Maximum plasma concentration of ERAS-254 and trametinib |
7. |
Area under the curve (AUC):Stage 1 only [ Time Frame: Study Day 1 up to Day 29 ]
Area under the plasma concentration-time curve |
Area under the curve (AUC):Stage 1 only [ Time Frame: Study Day 1 up to Day 29 ]
Area under the plasma concentration-time curve |
8. |
Quality of Life: To assess disease and treatment-related QOL in patients with NRASm melanoma. [ Time Frame: Assessed up to 24 months from time of first dose ]
Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire [QLQ]-C30 subscales and PRO CTCAE® symptom items specific to the potential cutaneous toxicities. |
Quality of Life: To assess disease and treatment-related QOL in patients with NRASm melanoma. [ Time Frame: Assessed up to 24 months from time of first dose ]
Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire [QLQ]-C30 subscales and PRO CTCAE® symptom items specific to the potential cutaneous toxicities. |
Other Outcome Measures: | |
1. |
Duration of Response (DOR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) |
Duration of Response (DOR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) |
2. |
Overall Response Rate (ORR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) |
Overall Response Rate (ORR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) |
3. |
Disease Control Rate (DCR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) |
Disease Control Rate (DCR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]
Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) |