MAPK Inhibitors + Pembrolizumab for Melanoma
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores how a combination of drugs might treat melanoma that cannot be surgically removed or has spread. The study tests pembrolizumab (Keytruda) with trametinib (Mekinist) and dabrafenib (Tafinlar, a type of MAPK inhibitor) to determine if these drugs can work together against the cancer. Suitable participants have confirmed melanoma that is metastatic or inoperable and have not previously tried similar treatments. The trial divides participants into two groups based on specific genetic markers called BRAFV600 mutations. Participants must be willing to undergo biopsies and comply with trial requirements. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in melanoma treatment.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received chemotherapy, radiation, or certain other cancer treatments within 2 weeks before starting the trial. It's best to discuss your specific medications with the trial team.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that the combination of pembrolizumab, dabrafenib, and trametinib is generally safe for patients with melanoma. Studies found that patients with BRAFV600E/K-mutant melanoma tolerated the combination well, although some side effects occurred. These side effects were usually manageable and did not outweigh the treatment's benefits.
For the combination of pembrolizumab and trametinib, safety remained manageable. Some patients experienced side effects, but these were considered acceptable given the potential benefits.
This trial is in phase 2, indicating that the treatment has already passed initial safety tests in earlier trials. While risks remain, the treatments are generally well-tolerated.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination of MAPK inhibitors like Dabrafenib and Trametinib with Pembrolizumab for treating melanoma because these treatments target specific pathways that drive cancer growth. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Dabrafenib and Trametinib specifically inhibit proteins in the MAPK pathway, which is often mutated in melanoma. The combination with Pembrolizumab, an immunotherapy that helps the immune system recognize and fight cancer cells, offers a dual approach by not only halting tumor growth but also enhancing the body's natural defenses against the cancer. This targeted and comprehensive strategy has the potential to improve outcomes for patients with BRAFV600 mutations and those with wild-type BRAF, offering hope for more effective and personalized melanoma treatment.
What evidence suggests that this trial's treatments could be effective for melanoma?
Research has shown that using dabrafenib and trametinib together treats advanced melanoma more effectively than using either drug alone. In this trial, participants with BRAFV600 mutant melanoma will receive a combination of pembrolizumab, dabrafenib, and trametinib. Studies indicate that pembrolizumab alone is effective for advanced melanoma. Participants with BRAFV600 wild type melanoma in this trial will receive pembrolizumab combined with trametinib. Combining pembrolizumab with dabrafenib and trametinib has shown promising results, possibly surpassing the effectiveness of pembrolizumab alone. This combination has been linked to longer survival and better outcomes for patients with metastatic melanoma. These findings suggest that these drug combinations hold strong potential for treating this condition.16789
Who Is on the Research Team?
Ryan J Sullivan, MD
Principal Investigator
Massachusetts General Hospital
Are You a Good Fit for This Trial?
Adults with confirmed metastatic or unresectable melanoma, measurable disease, known BRAFV600 mutation status, and willing to undergo biopsies can join. They may have had certain prior treatments but not specific recent therapies or surgeries. Those with major organ function issues, active infections like HIV/Hepatitis B/C, autoimmune diseases requiring treatment in the past 2 years, a history of certain lung conditions, live vaccines within 30 days before the trial start date, pregnancy or other serious illnesses are excluded.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive pembrolizumab intravenously every three weeks, with dabrafenib and trametinib taken orally every twelve hours for BRAFV600 mutant, or trametinib alone for BRAFV600 wild type
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments for clinical benefit at 6 months
Long-term Follow-up
Overall survival and progression-free survival are assessed up to 62 months
What Are the Treatments Tested in This Trial?
Interventions
- Dabrafenib
- Pembrolizumab
- Trametinib
Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications:
- Unresectable or metastatic melanoma with a BRAF V600 mutation
- Adjuvant treatment of melanoma with a BRAF V600 mutation
- Unresectable or metastatic melanoma with a BRAF V600E mutation
- Adjuvant treatment of melanoma with a BRAF V600E or V600K mutation
- Metastatic non-small cell lung cancer with a BRAF V600E mutation
- Unresectable or metastatic melanoma with a BRAF V600 mutation
- Adjuvant treatment of melanoma with a BRAF V600 mutation
- Unresectable or metastatic melanoma with a BRAF V600 mutation
Find a Clinic Near You
Who Is Running the Clinical Trial?
Massachusetts General Hospital
Lead Sponsor
Merck Sharp & Dohme LLC
Industry Sponsor
Chirfi Guindo
Merck Sharp & Dohme LLC
Chief Marketing Officer since 2022
Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme LLC
Chief Executive Officer since 2021
JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University