BRAF Mutation: Consider BRAF Inhibitors (e.g. PLX4032) & Ipilimumab/Yervoy

Your data matches Subtype 1.1 defined in the Melanoma Molecular Disease Model (MMDM). This subtype harbors mutations in the BRAF gene, the most common of which is the V600E mutation. Several classes of drugs (summarized below) may be relevant to this subtype. Investigational drugs within each class are being tested in melanoma.

Top drugs to consider:

PLX4032: This BRAF inhibitor has shown widespread efficacy in clinical trials on patients with the BRAF mutation, V600E. It is currently available from Roche on a compassionate use basis (see trial).

Ipilimumab/Yervoy: This CTLA-4 inhibitor has demonstrated increased overall survival in a small subset of melanoma patients. It was approved by the FDA in March 2011 for advanced melanoma and is also currently available from Bristol-Myers Squibb on a compassionate use basis (see trial).

GSK2118436: This BRAF inhibitor has shown robust efficacy in clinical trials on patients with the BRAF mutation, V600E. Interestingly, this drug resulted in shrinkage of brain metastatic lesions in some patients and is currently in Phase 2 trial for BRAF mutant patients with brain metastases (see trial).

Summary

Subtype

Subtype 1.1

Potentially Relevant Drug Classes

Clinical Trials

Details of your condition will determine eligibility for any specific trial. To select clinical trials for which you may be qualified, click here. Also, ask your doctor for more information.

Select Clinical Trials

Trial	Status	Phase
A Study of RO5185426 in Patients With Metastatic Melanoma [NCT01248936]		Expanded access
A Study of RO5185426 in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3) [NCT01006980]		Phase 3
Compassionate Use Trial for Unresectable Melanoma With Ipilimumab [NCT00495066]		Expanded access
A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma [NCT01153763]		Phase 2
Study of XL281 in Adults With Solid Tumors [NCT00451880]		Phase 1
A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma [NCT00304525]		Phase 1
Investigate Safety, Pharmacokinetics and Pharmacodynamics of GSK2118436 and GSK1120212 [NCT01072175]		Phase 1
A Phase I Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2118436 in Subjects With Solid Tumors [NCT00880321]		Phase 1
AZD8330 First Time in Man in Patients With Advanced Malignancies [NCT00454090]		Phase 1
MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery [NCT00866177]		Phase 2
Brief Title: Study to Determine Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Subjects Previously Treated With a BRAF Inhibitor [NCT01037127]		Phase 2
A Dose-Escalating Study of RO4987655 in Patients With Advanced Solid Tumors [NCT00817518]		Phase 1
Open-label Study to Investigate the Safety, PK, and Pharmacodynamics of GSK1120212 in Subjects With Solid Tumors or Lymphoma [NCT00687622]		Phase 1
Phase 1 Dose-escalation PK/PD Trial in Advanced Cancer Patients [NCT00610194]		Phase 1
RDEA119 and Sorafenib Combination Dose Escalation Study [NCT00785226]		Phase 1
Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients [NCT00936221]		Phase 2
Safety Study of PLX4032 in Patients With Solid Tumors [NCT00405587]		Phase 1
Randomised Study to Compare the Efficacy of AZD6244 vs TMZ [NCT00338130]		Phase 2
A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma [NCT01001299]		Phase 1
A Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma [NCT00949702]		Phase 2

Potentially Relevant Drugs

Drug	Other names	Drug Target	Manufacturer	Status
PLX4032	RO5185426, RG7204	BRAF	Hoffmann-La Roche	In clinical development for melanoma, also available on a compassionate use basis.
Ipilimumab	Yervoy, MDX-010, MDX-101, BMS-734016	CTLA-4	Bristol-Myers Squibb	Approved for metastatic melanoma, in development for non small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and metastatic hormone-refractory prostate cancer.
GSK2118436		BRAF	GlaxoSmithKline	In phase 3 trial for BRAF mutant patients with advanced melanoma and in phase 2 trial for BRAF mutant patients with brain metastases
RAF265	CHIR-265	ARAF	Novartis	In Phase 1 for malignant melanoma
XL281		RAF	Exelixis	In Phase I for solid tumors
AZD8330	-	MEK	AstraZeneca	In Phase I for advanced malignancies
AZD6244	ARRY-142886	MEK	AstraZeneca	In phase 2 development for various cancers including melanoma, breast cancer, colon cancer, lung cancer, kidney cancer etc.
GSK1120212	-	MEK	GlaxoSmithKline	In phase 2/3 for melanoma; In phase 1 for solid tumors/ lymphoma
RDEA119	-	MEK	Ardea Biosciences	In Phase I for advanced cancer
RO4987655	-	MEK	Roche	In Phase I with advanced solid tumors
XL518	GDC-0973	MEK	Genentech	In Phase I for solid tumors
AT13387	-	Hsp90	Astex	In Phase I for solid tumors

Publication	Reference
B-RAF inhibitors: an evolving role in the therapy of malignant melanoma	Shepherd C, Puzanov I, Sosman JA. Curr Oncol Rep. 2010 May;12(3):146-52.
Inhibition of mutated, activated BRAF in metastatic melanoma.	Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. N Engl J Med. 2010 Aug 26;363(9):809-19.
Improved survival with ipilimumab in patients with metastatic melanoma.	Hodi FS et.al. N Engl J Med. 2010 Aug 19;363(8):711-23

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BRAF Mutation: Consider BRAF Inhibitors (e.g. PLX4032) & Ipilimumab/Yervoy

Summary

Details of your condition will determine eligibility for any specific trial. To select clinical trials for which you may be qualified, click here. Also, ask your doctor for more information.