Prescribing information

 

   

Robust response in patients with BRAF-positive metastatic melanoma and brain metastases

TAFINLAR (dabrafenib) + MEKINIST (trametinib) is a targeted therapy demonstrating clinical evidence of activity in the brain1–3

 

Metastatic melanoma has a high risk of spreading to the central nervous system.4,5

40% to 60% of patients with metastatic melanoma develop brain metastases as their disease progresses.6

TAFINLAR + MEKINIST demonstrates an intracranial response (IR) in patients with BRAF V600-positive metastatic melanoma and brain metastases.1–3

Key Clinical Data Insights From COMBI-MB Trial

In the COMBI-MB trial, TAFINLAR + MEKINIST had a robust response in patients with BRAF V600-positive metastatic melanoma and brain metastases3

COMBI-MB was an open-label Phase II trial that evaluated TAFINLAR + MEKINIST in four patient cohorts with melanoma brain metastases (n=125).3

 

Key eligibility criteria3

  • Cutaneous melanoma metastatic to the brain

  • BRAF V600D/E/K/R mutation positive

  • <2 prior metastatic melanoma systemic treatments (prior treatment with BRAF or MEK inhibitors was not permitted)

  • Corticosteroids permitted; stable or decreasing dose only for Cohorts A-C

Chart showing the patient eligibility criteria

BID, twice daily; ECOG PS, Eastern Cooperative Oncology Group performance status; PFS, progression-free survival; QD, once daily.

 

Primary endpoint: investigator-assessed IR in Cohort A (BRAF V600E-positive patients with asymptomatic melanoma brain metastases, no local brain-directed therapy, and ECOG performance status of 0 or 1).*

Secondary endpoints: IR rate in Cohorts B, C, and D; extracranial response (ER) and overall response (OR) rates; intracranial, extracranial, and overall DCRs; duration of IR, ER, and OR; PFS; OS; and safety.

 

*Null hypothesis: IR rate of <35% in Cohort A (based on activity of dabrafenib monotherapy in the BREAK-MB trial).7

In the COMBI-MB clinical trial, 44 (58%; 95% CI 46–69) of 76 patients in Cohort A had an investigator-assessed IR3*

 

Intracranial Response (Cohort A)3*

Pie chart highlighting an Intracranial Response (Cohort A) or 58%. The graph also shows that 78% of patients had intercranaial disease control and 4% acheived complete response

*Patient cohorts: Cohort A included patients with BRAF V600E mutation, asymptomatic melanoma brain metastases, without local brain-directed therapy, and ECOG PS ≤1 (n=76); Cohort B included patients with BRAF V600E mutation, asymptomatic melanoma brain metastases, with local brain-directed therapy, and ECOG PS ≤1 (n=16); Cohort C included patients with BRAF V600D/K/R mutation, asymptomatic melanoma brain metastases, with or without local brain-directed therapy, and ECOG PS ≤1 (n=16); Cohort D included patients with BRAF V600D/E/K/R mutation, symptomatic melanoma brain metastases, with or without prior local brain-directed therapy, and ECOG PS ≤2 (n=17). Due to small sample size, results in Cohorts B, C and D should be interpreted with caution. CR, complete response; PR, partial response; SD, stable disease.

  • Overall, the median duration of IR was 6.5 months (95% CI, 4.9-10.3).3
  • IR rates of 56% (n=9/16), 44% (n=7/16), and 59% (n=10/17) in Cohorts B, C, and D, respectively.3

 

Safety data: COMBI-MB Trial Results

  • Adverse events (AEs) of any grade were observed in 98% of patients (n=123/125), with 48% of patients (n=60/125) reporting one or more Grade 3/4 event.3
  • Dose interruptions and reductions due to AEs were observed in 50% (n=62/125) and 22% (n=28/125) of patients, respectively.3
  • Discontinuations due to AEs occurred in 10% of patients (n=12/125).3
  • The most common AEs in this study included pyrexia (54%, n=67/125), nausea (32%, n=40/125), and chills (30%, n=37/125).3

References

  1. TAFINLAR (dabrafenib) Summary of Product Characteristics.
  2. MEKINIST (trametinib) Summary of Product Characteristics.
  3. Davies MA, et al. Lancet Oncol 2017;18:863-873.
  4. Cohen JV, et al. Pigment Cell Melanoma Res 2016;29:627-642.
  5. Sampson JH, et al. J Neurosurg 1998;88:11-20.
  6. Zhang D, et al. Melanoma Res 2019;29:77-84.
  7. Long GV, et al. Lancet Oncol 2012;13:1087-1095.
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UK | April 2022 | 142953
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
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