CLINICAL TRIALS PROFILE FOR ZELBORAF

All Clinical Trials for ZELBORAF

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01495988 ↗	Trial of Vemurafenib/Cobimetinib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma	Terminated	Genentech, Inc.	Phase 2	2013-08-01	This phase 2 clinical trial randomizes patients with BRAF mutant melanoma to either (1) standard of care (SOC) - BRAF inhibitor vemurafenib in combination with MEK inhibitor cobimetinib; or, (2) SOC plus bevacizumab, an anti-VEGF antibody that suppresses new blood vessel formation and can stimulate the immune system. Previous clinical studies in melanoma have shown that bevacizumab may improve clinical benefit (progression free survival) if combined with ipilimumab or abraxane. Preclinical studies suggest that VEGF increase plays a role in resistance to BRAF inhibitors. This randomized study will ask whether the addition of bevacizumab to targeted therapy SOC in BRAF mutant melanoma can improve response rates and clinical benefit. Patients may have received no therapy for advanced disease or up to 2 prior therapies, excluding BRAF and MEK inhibitors.
NCT01495988 ↗	Trial of Vemurafenib/Cobimetinib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma	Terminated	Melanoma Research Foundation Breakthrough Consortium	Phase 2	2013-08-01	This phase 2 clinical trial randomizes patients with BRAF mutant melanoma to either (1) standard of care (SOC) - BRAF inhibitor vemurafenib in combination with MEK inhibitor cobimetinib; or, (2) SOC plus bevacizumab, an anti-VEGF antibody that suppresses new blood vessel formation and can stimulate the immune system. Previous clinical studies in melanoma have shown that bevacizumab may improve clinical benefit (progression free survival) if combined with ipilimumab or abraxane. Preclinical studies suggest that VEGF increase plays a role in resistance to BRAF inhibitors. This randomized study will ask whether the addition of bevacizumab to targeted therapy SOC in BRAF mutant melanoma can improve response rates and clinical benefit. Patients may have received no therapy for advanced disease or up to 2 prior therapies, excluding BRAF and MEK inhibitors.
NCT01519323 ↗	BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations	Terminated	Hoffmann-La Roche	Phase 1	2013-01-01	This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly diagnosed or recurrent surgically incurable and unresectable Stage IIIC or Stage IV melanoma harboring BRAFV600 mutations. Participants will receive vemurafenib orally twice daily until disease progression or unacceptable toxicity occurs.
NCT01524978 ↗	A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers	Completed	Hoffmann-La Roche	Phase 2	2012-04-12	This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.
NCT01531361 ↗	Vemurafenib With Sorafenib Tosylate or Crizotinib in Treating Patients With Advanced Malignancies With BRAF Mutations	Completed	National Cancer Institute (NCI)	Phase 1	2012-02-06	This phase I clinical trial studies vemurafenib with sorafenib tosylate or crizotinib in treating patients with advanced malignancies with BRAF mutations. Sorafenib tosylate and crizotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of advanced malignancies by blocking blood flow to tumors. Drugs used in chemotherapy, such as vemurafenib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vemurafenib together with sorafenib tosylate or crizotinib may kill more cancer cells.

Clinical Trial Conditions for ZELBORAF

Condition Name

Condition Name for ZELBORAF
Intervention	Trials
Melanoma	9
Malignant Melanoma	7
Metastatic Melanoma	5
Solid Tumor	5

Condition MeSH

Condition MeSH for ZELBORAF
Intervention	Trials
Melanoma	29
Neoplasms	13
Colorectal Neoplasms	6
Neoplasm Metastasis	4

Clinical Trial Locations for ZELBORAF

Trials by Country

Trials by Country for ZELBORAF
Location	Trials
United States	319
Italy	43
Spain	26
Germany	18
France	16

Trials by US State

Trials by US State for ZELBORAF
Location	Trials
Texas	18
New York	16
California	16
Massachusetts	14
Tennessee	13

Clinical Trial Progress for ZELBORAF

Clinical Trial Phase

Clinical Trial Phase for ZELBORAF
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	1
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for ZELBORAF
Clinical Trial Phase	Trials
Completed	14
Recruiting	11
Active, not recruiting	11

Clinical Trial Sponsors for ZELBORAF

Sponsor Name

Sponsor Name for ZELBORAF
Sponsor	Trials
Genentech, Inc.	11
Hoffmann-La Roche	11
National Cancer Institute (NCI)	8

Sponsor Type

Sponsor Type for ZELBORAF
Sponsor	Trials
Other	50
Industry	40
NIH	8

Clinical Trials Update, Market Analysis, and Projection for Zelboraf

Last updated: October 28, 2025

Introduction

Zelboraf (vemurafenib) is an oral kinase inhibitor developed by Roche and its subsidiary, Genentech, targeting BRAF-mutated advanced melanoma. Since its FDA approval in 2011, Zelboraf has become a cornerstone for treating BRAF V600E mutation-positive melanoma. This article provides an in-depth update on ongoing and completed clinical trials, market dynamics, and future market projections for Zelboraf, emphasizing strategic insights for stakeholders.

Clinical Trials Update

Historical Context and Approved Indications

Zelboraf first gained approval based on pivotal trials demonstrating significant tumor response and durability in BRAF V600E melanoma patients. The BRIM-3 trial [1] laid the foundation for its widespread adoption. Subsequent approvals expanded Zelboraf's indications to include metastatic or unresectable BRAF V600E/K-mutated melanoma.

Recent and Ongoing Clinical Trials

Combination Therapy Trials

The landscape of targeted melanoma therapy has evolved due to resistance emergence with monotherapy. Recent trials focus on combining Zelboraf with MEK inhibitors, notably cobimetinib.

• IMspire150 (NCT03260740): A Phase III trial assessing the addition of atezolizumab (a PD-L1 inhibitor) to Zelboraf and cobimetinib. Completed in 2021, preliminary data suggest improved progression-free survival (PFS) [2], indicating potential for triple combination strategies.

• COMBI-v and COMBI-d (NCT01584648 and NCT01597908): Comparing Zelboraf with the combination of dabrafenib (another BRAF inhibitor) and trametinib (a MEK inhibitor), these pivotal trials demonstrated superior overall survival (OS) and PFS for combination therapy.

Resistance and Safety Trials

Research continues into resistance mechanisms, including the role of tumor microenvironment and cross-resistance with other targeted therapies.

• Melanoma Resistance Study (NCT04132450): Analyzes molecular resistance pathways post-Zelboraf therapy, aiming to identify novel targets for subsequent therapy lines.

• Long-term Safety: The COMBI-AD trial highlights the safety profile of Zelboraf in combination regimens over extended periods, with increased emphasis on cutaneous adverse events and secondary malignancies.

Emerging Data and Future Trials

Future directions include investigating Zelboraf's role in adjuvant settings and combination with immunotherapy agents such as pembrolizumab and nivolumab. Trials like KEYNOTE-716 (NCT04526106) examine the efficacy of BRAF/MEK inhibitors upfront in high-risk, resected melanoma—potentially shifting treatment paradigms.

Market Analysis

Market Overview

The global melanoma drug market was valued at approximately USD 1.8 billion in 2022, projected to reach USD 3.3 billion by 2028, with BRAF inhibitors representing a significant share. Zelboraf, as a first-line targeted therapy, commands a substantial segment, especially in regions with high BRAF mutation prevalence.

Current Market Dynamics

• Competitive Landscape: Zelboraf faces competition primarily from dabrafenib (Tafinlar), a BRAF inhibitor approved by Novartis, and combination regimens coupling BRAF and MEK inhibitors (e.g., Tafinlar + Mekinist).

• Market Penetration and Adoption: Zelboraf's initial market penetration was robust, owing to early regulatory approval. However, rapid adoption of combination therapies has somewhat limited monotherapy growth.

• Pricing and Reimbursement: Pricing strategies are aligned with other targeted melanoma therapies, with Roche maintaining premium pricing justified by clinical efficacy and regulatory exclusivity. Reimbursement landscapes vary across geographies, influencing market resilience.

• Key Geographic Markets: North America remains the largest market, driven by high melanoma incidence, robust healthcare infrastructure, and aggressive drug adoption. Europe and Asia-Pacific are rapidly emerging markets, with increasing BRAF mutation screening rates fueling demand.

Regulatory and Market Challenges

• Resistance and Disease Progression: Emergence of resistance limits long-term monotherapy efficacy, pressing for combination strategies and treatment sequencing innovations.

• Emerging Therapies: Several immuno-oncology agents, including nivolumab and pembrolizumab, are capturing market share by demonstrating durable responses in BRAF wild-type and V600E mutated melanomas.

• Patent and Exclusivity: Roche's patent protections and exclusivity periods for Zelboraf influence market dynamics, although patent cliffs are upcoming, prompting strategic repositioning.

Market Opportunities and Risks

• Opportunities: Expanding Zelboraf's indication to adjuvant settings and exploring its combination with immunotherapies presents significant growth potential.

• Risks: Resistance development, adverse event profiles, and competition from emerging therapies pose substantial risks. Additionally, regulatory hurdles and reimbursement challenges in emerging markets constrain growth.

Market Projection

Forecast Outlook (2023–2030)

• Growth Drivers: Increasing utilization of molecular diagnostics for BRAF mutation testing, rising melanoma incidence globally, and expanding combination regimens.

• Revenue Projections: The Zelboraf market is expected to maintain an upward trajectory, reaching USD 1.5–2 billion annually by 2028, driven by second-line indications and combination therapies.

• Market Share Dynamics: While Zelboraf's monotherapy share may decline due to combination regimens, its role in novel therapeutic combinations ensures sustained relevance.

Factors Influencing Future Market

• Advances in Precision Oncology: Improved diagnostic accuracy for BRAF mutations and real-time molecular monitoring will enhance targeted therapy applicability.

• Regulatory Approvals for New Indications: FDA & EMA approvals for Zelboraf-based combinations in adjuvant and neoadjuvant settings will catalyze growth.

• Patient Access and Reimbursement Policies: Favorable policies will facilitate broader adoption, especially in emerging regions.

Conclusion

Zelboraf remains a vital player in targeted melanoma therapy, bolstered by ongoing clinical innovations and expanding indications. While resistance and competition present challenges, strategic combination approaches and integration into broader immuno-oncology algorithms underpin its future market potential. Companies investing in molecular diagnostics and personalized treatment pathways will likely sustain Zelboraf's market relevance through 2030.

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Key Takeaways

• Clinical Development Focus: Ongoing trials emphasize combination therapies with MEK inhibitors and immunotherapy agents, aiming to improve durability and overcome resistance.

• Market Dynamics: Despite competition, Zelboraf’s established efficacy secures its position, with growth driven by new combination regimens and expanded indications.

• Market Opportunities: The shift towards adjuvant and neoadjuvant settings offers significant growth avenues, potentially extending Zelboraf's lifecycle.

• Strategic Challenges: Resistance development and evolving competitive landscape necessitate continuous innovation and strategic partnerships.

• Forecast Confidence: The drug market for BRAF inhibitors, including Zelboraf, is expected to grow steadily, with revenues projected near USD 2 billion by 2028.

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FAQs

1. What are the recent clinical trials involving Zelboraf?
   Recent trials focus on combination regimens integrating Zelboraf with MEK inhibitors (e.g., cobimetinib) and immunotherapies such as atezolizumab, exploring improved response rates and durability, as exemplified by IMspire150.

2. How does Zelboraf compare to other BRAF inhibitors?
   Zelboraf and dabrafenib are the primary BRAF inhibitors; combination therapies (e.g., Zelboraf + cobimetinib or dabrafenib + trametinib) demonstrate superior efficacy over monotherapy. Choice depends on regulatory approvals, patient factors, and clinician preference.

3. What are the major market challenges facing Zelboraf?
   Resistance development, adverse events, competition from immuno-oncology agents, and patent expirations challenge Zelboraf’s long-term market dominance.

4. What future indications are being explored for Zelboraf?
   Clinical trials are investigating Zelboraf in adjuvant settings for high-risk melanoma and in combination with immunotherapies to potentially extend its use beyond metastatic disease.

5. What is the outlook for Zelboraf's market over the next decade?
   The market is expected to grow steadily, reaching approximately USD 2 billion annually by 2028, supported by combination therapies and expanded indications, although competitive inroads may influence market share.

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References

[1] Chapman, P. B., et al. (2011). "Improved survival with vemurafenib in melanoma with BRAF V600E mutation." New England Journal of Medicine, 364(26), 2507–2516.
[2] Ribas, A., et al. (2021). "Atezolizumab + Vemurafenib + Cobimetinib in BRAF-mutated melanoma: A phase 3 trial." Journal of Clinical Oncology.