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Vemurafenib

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Valine

all eligible patients entering the study will receive oral Vemurafenib as monotherapy.

Vemurafenib ZELBORAF 240 mg tablets Per OS 960 mg twice daily, to a total daily dose of 1,920 mg Cycles are defined in 28-day periods Disease response will be assessed every 8 weeks Safety will be assessed continuously

Treatment will be pursed until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient refusal.

Vemurafenib is a low molecular weight, orally available, inhibitor of BRAF serine-threonine kinase. Mutations in the BRAF gene which substitute the valine at amino acid position 600 result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation

Jean-Yves PI Blay, MD

Patients with metastatic or unresectable locally advanced malignancies harboring BRAF genomic alterations, the biological target of vemurafenib, and who are no more amenable to curative treatment.

To explore the efficacy of vemurafenib as a single agent across diverse type of tumors guided by the presence of identified activating molecular alterations in the vemurafenib target gene, per cohort.

This is a biology driven, trans-tumoral, multicentric phase II trial assessing the efficacy and the safety of the targeted agent vemurafenib as a monotherapy in cohorts of patients with identified activating molecular alterations in BRAF gene. A cohort is defined by a pathology and a BRAF- alteration (eg ovarian cancer with BRAF V600 mutation).

To explore the efficacy of vemurafenib per pathology and per target. To assess the safety profile of vemurafenib. To explore whether molecularly driven, high quality multi-tumor screening phase II trials are feasible in the French multiinstitutional, multidisciplinary setting.

To investigate the additional molecular mechanisms in patients with tumor response versus patients without tumor response within the same cohort.

The study will include 11 cohorts of adult patients with the following cancers and alterations:

* NSCLC V600 mutated
* Ovarian cancer V600 mutated
* Cholangiocarcinoma V600 mutated
* Thyroid cancer V600 mutated
* Prostatic cancer V600 mutated
* Bladder cancer V600 mutated
* Sarcoma/GIST V600 mutated
* Multiple myeloma V600 mutated
* Chronic Lymphocytic Leukemia (CLL) V600 mutated
* Hairy cell leukaemia (HCL) V600 mutated (this excludes Hairy Cell Leukemia variant types, marginal zone splenic lymphoma (MZL), splenic red pulp lymphoma (SRPL) patients)
* Other pathology / other alteration than those pre-defined above.

The cohort named "Other" will include adult patients with tumor harboring BRAF genomic alterations only tested via emerging biomarkers programs or molecular pangenomic programs:

* with any other non-predefined pathology harboring a V600 mutation
* Same or other non-predefined pathology harboring non V600 activating mutations
* Same or other non-predefined pathology harboring BRAF amplifications.

Phase 2 Study Assessing Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations

Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations

RECIST for solid tumors, International Myeloma Working Group Response Criteria for myeloma, IWCLL for CLL, clinical exam, blood tests (blood count) and bone marrow exam for Hairy Cell Leukemia.

The assessment of safety will be based mainly on the frequency of adverse events coded using the common toxicity criteria (CTC-V4.0) grade.

National Cancer Institute, France

Fondation ARC

Hoffmann-La Roche

UNICANCER

Spots Global Cancer Trial Database for biological vemurafenib targets braf