Novartis Tafinlar + Mekinist receives FDA approval for first tumor-agnostic indication for BRAF V600E solid tumors

• Tafinlar + Mekinist, the worldwide targeted therapy leader in BRAF/MEK-inhibition, is the first and only therapy to be approved with a tumor-agnostic indication for adult and pediatric patients with solid tumors that have a BRAF V600E mutation^1,2
• Approval supported by results from Phase II ROAR and NCI-MATCH studies demonstrating overall response rates up to 80% in patients with BRAF V600E solid tumors^1,2
• BRAF mutations drive tumor growth across more than 20 tumor types, including thyroid, brain and gynecologic cancers^3,4

EAST HANOVER, N.J., June 22, 2022 /PRNewswire/ -- Novartis today announced the US Food and Drug Administration (FDA) granted accelerated approval for Tafinlar^® (dabrafenib) + Mekinist^® (trametinib) for the treatment of adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options^1,2. In accordance with the Accelerated Approval Program, continued approval for this indication may be contingent upon  verification and description of clinical benefit in a confirmatory trial(s). Tafinlar + Mekinist is the first and only BRAF/MEK inhibitor to be approved with a tumor-agnostic indication for solid tumors carrying the BRAF V600E mutation, which drives tumor growth in more than 20 different tumor types, and it is the only BRAF/MEK inhibitor approved for use in pediatric patients^1,2.   

"The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple BRAF-positive tumor types, including in some patients with rare cancers who have no other treatment options available," said principal investigator Dr. Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, Texas. "Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors." 

The FDA approval was based on clinical efficacy and safety demonstrated in three clinical trials. In the Phase II ROAR (Rare Oncology Agnostic Research) basket study and the NCI-MATCH Subprotocol H study, Tafinlar + Mekinist resulted in overall response rates of up to 80% in patients with BRAF V600E solid tumors, including high- and low-grade glioma, biliary tract cancer and certain gynecological and gastrointestinal cancers. An additional study (Study X2101) demonstrated the clinical benefit and acceptable safety profile of Tafinlar + Mekinist in pediatric patients^1,2. 

"Tackling cancer is complex, which is why it is so important that we continue to follow the science as we pursue meaningful advances and new approaches to treating cancer," said Reshema Kemps-Polanco, Head, Novartis Oncology US. "We are grateful to the patients, and to the multitude of individuals and teams working together to make this latest approval possible as we strive to do more for more people living with cancer." 

The safety profile of Tafinlar + Mekinist observed in these studies was consistent with the known safety profile in other approved indications.  

BRAF mutations have been identified as drivers of cancer growth across a wide range of solid tumors, including in rare cancer types that can be challenging to study in Phase III trials and often have limited treatment options^3,4. BRAF V600E is the most common type of BRAF mutation, accounting for up to 90% of BRAF-mutant cancers³.  

Full prescribing information for Tafinlar + Mekinist can be found at
https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf and
https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.  

About Tafinlar + Mekinist 
The combination of Tafinlar + Mekinist, the worldwide targeted therapy leader in BRAF/MEK-inhibition research and patients reached, may help to slow tumor growth by blocking signals associated with the BRAF and MEK kinases that are implicated in the growth of various types of cancer^1-5. Tafinlar + Mekinist has been studied in more than 6,000 BRAF-positive patients in more than 20 ongoing and completed trials, including in pediatric patients 1 year of age and older, and has been prescribed to more than 200,000 patients worldwide⁵. 

Tafinlar + Mekinist is also approved for use in BRAF-positive unresectable or metastatic melanoma, as an adjuvant treatment for BRAF-positive melanoma after surgery, in BRAF-positive metastatic non-small cell lung cancer, and in BRAF-positive anaplastic thyroid cancer^1,2. Tafinlar + Mekinist is not indicated for treatment of patients with colorectal cancer or for treatment of patients with wild-type BRAF solid tumors. 

Indication and Important Safety Information

TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

• that has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
• that has a certain type of abnormal "BRAF" (V600E or V600K mutation-positive) gene

TAFINLAR and MEKINIST are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal "BRAF" gene from coming back after the cancer has been removed by surgery.

TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal "BRAF V600E" gene.

TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

• that has spread to other parts of the body and you have no satisfactory treatment options and
• that has a certain type of abnormal "BRAF" gene

TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat solid tumors in adults and children 6 years of age and older:

• that cannot be removed by surgery or have spread to other parts of the body, and that have gotten worse (progressed) and you have no satisfactory treatment options and
• that have a certain type of abnormal "BRAF" gene

The effectiveness of TAFINLAR and MEKINIST in these patients is based on 2 adult studies and 1 pediatric study that measured 2 types of response to treatment (response rate and duration of response). No clinical information is available to show if these patients treated with TAFINLAR and MEKINIST live longer or if their symptoms improve. Ongoing studies exist to determine how TAFINLAR and MEKINIST works over a longer period.

 TAFINLAR, in combination with MEKINIST, is not for use in treating people with colorectal cancer or wild-type BRAF solid tumors. MEKINIST should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that TAFINLAR and MEKINIST, in combination, are right for you.

It is not known if TAFINLAR used in combination with MEKINIST is safe and effective in children younger than 6 years of age.

TAFINLAR and MEKINIST, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When TAFINLAR is used in combination with MEKINIST, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feeling weak, coughing up blood or blood clots, vomiting blood or their vomit looks like "coffee grounds," or red or black stools that look like tar.

MEKINIST, alone or in combination with TAFINLAR, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider right away if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

TAFINLAR, in combination with MEKINIST, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of TAFINLAR and MEKINIST can cause heart problems, including heart failure. A patient's heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

TAFINLAR, in combination with MEKINIST, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

TAFINLAR, in combination with MEKINIST, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with TAFINLAR in combination with MEKINIST but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of TAFINLAR in combination with MEKINIST. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with TAFINLAR in combination with MEKINIST. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.

TAFINLAR may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

TAFINLAR, in combination with MEKINIST, can cause new or worsening high blood pressure (hypertension). A patient's blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

For women of reproductive potential, TAFINLAR and MEKINIST, in combination, can harm your unborn baby. Your health care provider will do a test to see if you are pregnant before starting treatment with TAFINLAR and MEKINIST in combination. Use effective birth control (contraception) during treatment with TAFINLAR and MEKINIST in combination, and for 4 months after stopping treatment with TAFINLAR and MEKINIST.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with TAFINLAR and MEKINIST and for at least 4 months after the last dose of TAFINLAR and MEKINIST.

The most common side effects for patients with metastatic melanoma receiving the combination are pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma as adjuvant therapy receiving the combination are pyrexia, tiredness, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC receiving the combination are pyrexia, tiredness, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common side effects for adults with solid tumors that cannot be removed by surgery or have spread to other parts of the body who are receiving the combination are fever, tiredness, nausea, rash, chills, headache, bleeding, cough, vomiting, constipation, diarrhea, muscle and or joint aches, and swelling of arms and legs. The most common side effects for children with solid tumors that cannot be removed by surgery or have spread to other parts of the body who are receiving the combination are fever, rash, vomiting, tiredness, dry skin, cough, diarrhea, acne, headache, stomach-area (abdomen) pain, nausea, bleeding, constipation, and skin infection around fingernails or toenails.

Please see full Prescribing Information for TAFINLAR and MEKINIST at
https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf and
https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.

Disclaimer 
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "seek," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. 

About Novartis 
Novartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.  

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References 

1.     Tafinlar [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022. 
2.     Mekinist [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022. 
3.     Turski ML, et al. Mol Cancer Ther. 2016;15:533-547 
4.     Pratilas C, et al. Curr Top Microbiol Immunol. 2012;355:82-98. 
5.     Novartis data on file. 

SOURCE Novartis US