CLINICAL TRIALS PROFILE FOR BRAFTOVI

All Clinical Trials for BRAFTOVI

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03898908 ↗	Encorafenib and Binimetinib Before Local Treatment in Patients With BRAF Mutant Melanoma Metastatic to the Brain	Recruiting	MFAR	Phase 2	2019-07-18	Phase II clinical trial, with two cohorts of patients included in parallel, all with melanoma BRAF mutated and brain metastases without previous local treatment in the brain. Cohort 1 will include patients with asymptomatic brain metastases and cohort 2 will include patients with symptomatic brain metastasis.
NCT02902042 ↗	Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma	Completed	Prof. Dr. med. Dirk Schadendorf	Phase 1/Phase 2	2018-04-24	This study will investigate the influence of maintenance therapy on progression-free survival (PFS) and overall survival (OS) after combination therapy with BRAF/MEK (MAP-ERK kinase) inhibitors and PD-1 antibody pembrolizumab. In the safety phase I part the optimal dose of pembrolizumab in combination with BRAF inhibitor and MEK inhibitor and the safety of this three-drugs-combination regime will be determined. In the randomized part 2 different maintenance therapies will be tested for toxicity and efficacy. Patients with disease control after 6 months of triple therapy will be randomized to receive 2 different maintenance therapies further on, either continuation of triple therapy or administration of pembrolizumab alone.
NCT02910700 ↗	Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma	Recruiting	Bristol-Myers Squibb	Phase 2	2016-12-09	This phase II trial studies the side effects and how well nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib work in treating patients with BRAF-mutated stage III-IV melanoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Trametinib, dabrafenib, encorafenib, and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib may work better in treating patients with BRAF-mutated melanoma.
NCT02910700 ↗	Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma	Recruiting	National Cancer Institute (NCI)	Phase 2	2016-12-09	This phase II trial studies the side effects and how well nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib work in treating patients with BRAF-mutated stage III-IV melanoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Trametinib, dabrafenib, encorafenib, and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib may work better in treating patients with BRAF-mutated melanoma.
NCT02910700 ↗	Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma	Recruiting	M.D. Anderson Cancer Center	Phase 2	2016-12-09	This phase II trial studies the side effects and how well nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib work in treating patients with BRAF-mutated stage III-IV melanoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Trametinib, dabrafenib, encorafenib, and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib may work better in treating patients with BRAF-mutated melanoma.

Clinical Trial Conditions for BRAFTOVI

Condition Name

Condition Name for BRAFTOVI
Intervention	Trials
Metastatic Melanoma	4
Melanoma	4
Metastatic Rectal Adenocarcinoma	3
Metastatic Colon Adenocarcinoma	3

Condition MeSH

Condition MeSH for BRAFTOVI
Intervention	Trials
Melanoma	10
Colorectal Neoplasms	5
Adenocarcinoma	4
Brain Neoplasms	4

Clinical Trial Locations for BRAFTOVI

Trials by Country

+

−

Trials by Country for BRAFTOVI
Location	Trials
United States	63
Germany	17
Spain	12
Italy	7
Czechia	5

Trials by US State

+

−

Trials by US State for BRAFTOVI
Location	Trials
California	6
Texas	6
Michigan	4
Ohio	3
Florida	3

Clinical Trial Progress for BRAFTOVI

Clinical Trial Phase

Clinical Trial Phase for BRAFTOVI
Clinical Trial Phase	Trials
Phase 3	2
Phase 2/Phase 3	1
Phase 2	10

Clinical Trial Status

Clinical Trial Status for BRAFTOVI
Clinical Trial Phase	Trials
Recruiting	11
Not yet recruiting	7
Active, not recruiting	1

Clinical Trial Sponsors for BRAFTOVI

Sponsor Name

Sponsor Name for BRAFTOVI
Sponsor	Trials
National Cancer Institute (NCI)	9
Pfizer	5
M.D. Anderson Cancer Center	3

Sponsor Type

Sponsor Type for BRAFTOVI
Sponsor	Trials
Other	25
Industry	19
NIH	9

BRAFTOVI: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction to BRAFTOVI

BRAFTOVI (encorafenib), developed by Pfizer, is a BRAF kinase inhibitor that has been making significant strides in the treatment of various cancers, particularly those with the BRAF V600E mutation. This article will delve into the recent clinical trial updates, market analysis, and future projections for BRAFTOVI.

Clinical Trial Updates

PHAROS Trial: Long-Term Efficacy in NSCLC

The Phase 2 PHAROS clinical trial has provided compelling long-term data on the efficacy of BRAFTOVI in combination with MEKTOVI (binimetinib) for patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC). The trial demonstrated substantial antitumor activity, with a median progression-free survival (PFS) of 30.2 months and a median duration of response (DoR) of 40 months in treatment-naïve patients. For previously treated patients, the median PFS was 9.3 months and the median DoR was 16.7 months[1][4].

Objective Response Rates

The PHAROS trial showed an objective response rate (ORR) of 75% in treatment-naïve patients and 46% in previously treated patients. These results are among the longest observed for BRAF V600E-mutant metastatic NSCLC compared to historical outcomes, positioning BRAFTOVI + MEKTOVI as a promising first-line therapy[1][4].

Safety Profile

The safety profile of the BRAFTOVI + MEKTOVI combination has been consistent with previous findings, with no new safety concerns identified. Common treatment-related adverse events (TRAEs) included nausea, diarrhea, and fatigue, leading to dose reductions in 26% of patients and treatment discontinuation in 16% of patients[1][4].

Market Analysis

Market Share and Sales Projections

BRAFTOVI is poised to dominate the BRAF inhibitors market for melanoma, with forecasts indicating it will secure a 42% market share by 2028. This is expected to translate into $424 million in sales, surpassing Novartis' Tafinlar (dabrafenib), which is projected to capture 36% of the market with $364 million in sales[2][3].

Market Growth and Drivers

The BRAF kinase inhibitors market is anticipated to grow by USD 1.40 billion during 2023-2028, with a Compound Annual Growth Rate (CAGR) of 7.88%. Key drivers include the high target affinity and specificity of BRAF kinase inhibitors, patient assistance programs, and the increasing prevalence of cancer[5].

Competitive Landscape

BRAFTOVI, in combination with MEKTOVI, outperforms its competitors, such as Tafinlar (dabrafenib) combined with Mekinist (trametinib), in terms of efficacy, tolerability, and side effects. This combination is approved for melanoma that has spread or cannot be removed by surgery and is also effective in treating metastatic BRAF-mutated NSCLC[2][3].

Future Projections and Indications

Ongoing Clinical Trials

There are 27 ongoing Phase I-III clinical trials investigating the effectiveness of BRAFTOVI in various solid and hematological cancers. These trials include explorations of BRAFTOVI in earlier settings of metastatic colorectal cancer and the development of a next-generation brain-penetrant BRAF inhibitor[2][3].

Potential New Indications

BRAFTOVI is being explored for additional indications, such as relapsed multiple myeloma, metastatic brain tumors, and in combination with immunotherapy for melanoma. Approval for these indications could further strengthen its market position[2][3].

Regulatory Approvals

FDA and European Commission Approvals

BRAFTOVI + MEKTOVI was approved by the U.S. Food and Drug Administration (FDA) in October 2023 and by the European Commission in August 2024 for the treatment of metastatic BRAF-mutated NSCLC in newly diagnosed patients or those who received prior therapy but not BRAF inhibitors[1][3].

Key Takeaways

• Long-Term Efficacy: BRAFTOVI + MEKTOVI has shown sustained efficacy in patients with BRAF V600E-mutant metastatic NSCLC, with significant PFS and DoR.
• Market Dominance: BRAFTOVI is projected to command a 42% share of the BRAF inhibitors market for melanoma by 2028.
• Safety Profile: The combination has a manageable safety profile with common TRAEs including nausea, diarrhea, and fatigue.
• Future Indications: Ongoing trials are exploring BRAFTOVI in various cancers, including metastatic colorectal cancer and brain tumors.
• Regulatory Approvals: Recent approvals by the FDA and European Commission solidify its position in treating metastatic BRAF-mutated NSCLC.

FAQs

What is the current market share projection for BRAFTOVI in the BRAF inhibitors market for melanoma?

BRAFTOVI is projected to secure a 42% market share by 2028, with estimated sales of $424 million[2][3].

What are the key findings from the PHAROS trial for BRAFTOVI + MEKTOVI in NSCLC?

The PHAROS trial showed an ORR of 75% in treatment-naïve patients and 46% in previously treated patients, with median PFS and DoR that are among the longest observed for BRAF V600E-mutant metastatic NSCLC[1][4].

What are the common treatment-related adverse events associated with BRAFTOVI + MEKTOVI?

Common TRAEs include nausea, diarrhea, and fatigue, leading to dose reductions in 26% of patients and treatment discontinuation in 16% of patients[1][4].

What are the potential new indications being explored for BRAFTOVI?

BRAFTOVI is being explored for indications such as relapsed multiple myeloma, metastatic brain tumors, and in combination with immunotherapy for melanoma[2][3].

What regulatory approvals have been received for BRAFTOVI + MEKTOVI?

BRAFTOVI + MEKTOVI was approved by the FDA in October 2023 and by the European Commission in August 2024 for the treatment of metastatic BRAF-mutated NSCLC[1][3].

References

1. Pfizer's BRAFTOVI® + MEKTOVI® Shows Long-Term Clinically Meaningful Response in Patients with BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer. Pfizer Press Release, September 14, 2024.
2. Pfizer's Braftovi to command 42% share of BRAF inhibitors market for melanoma by 2028. Biopharma Reporter, March 21, 2024.
3. Pfizer's Braftovi to command 42 percent share of BRAF inhibitors market for melanoma by 2028. Financial Express, March 20, 2024.
4. Braftovi Plus Mektovi Demonstrates Sustained Efficacy in Patients with BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer. Pharm Exec, September 18, 2024.
5. BRAF Kinase Inhibitors Market 2024-2028. Research and Markets.