Melanoma Clinical Trials to Watch: March 2023

By Cody Barnett, MPH, MRA Senior Director of Communications & Patient Engagement | 27 March 2023 | News, Science, Treatment

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Clinical trials, and the patient volunteers who make them possible, are critical to advancing melanoma research. Clinical trials offer patients access to treatment approaches that may prove more beneficial than anything currently approved by the FDA. In addition, clinical trials drive our understanding of melanoma forward, improving future treatment options for all patients. Lack of awareness of and participation in clinical trials is one of the biggest obstacles to bringing new therapies to market1 and today there are more than 500 melanoma-focused clinical trials currently recruiting patients. 

In the Melanoma Clinical Trials to Watch article series, we’ll regularly highlight clinical trials that are currently recruiting patients, have recently shared exciting updates, or are blazing new trails.

Additional information about melanoma clinical trials – including questions to ask your doctor, benefits and risks, and tools to help you find trials that may be right for you – are available on MRA’s website.

Now Recruiting: Therapeutic Melanoma Vaccine for Patients with Advanced Melanoma:

Vaccines play an important role in keeping us healthy by protecting us from getting sick or by reducing the severity or duration of an illness. In addition to these preventive vaccines, researchers are also working to develop vaccines that treat disease, including melanoma, known as therapeutic vaccines.

BioNTech’s BNT111 investigational vaccine is made up of key mRNA sequences that teach your body how to make copies of four different antigens – or immune system triggers – that are found in melanoma (but not healthy cells). These antigen building instructions, completely harmless on their own, help to train the immune system to identify and seek out melanoma.

“With mRNA  vaccines, we hope to cut through the immune system clutter to create a robust immune response against melanoma,” said Dr. Adil Daud, professor and co-director of the Melanoma Center at the University of California, San Francisco (UCSF).

The BNT111-01 clinical trial is currently recruiting patients with advanced melanoma at 58 sites across the world. The Phase 2 clinical study testing BNT111, BioNTech’s mRNA melanoma vaccine, in combination with cemipilimab, a PD-1 checkpoint immunotherapy, or as single agents for patients with Stage 3 or 4 melanoma who have been previously treated with a PD-1 based checkpoint immunotherapy.

This Phase 2 trial is based on the Phase 1 Lipo-MERIT dose escalation trial (NCT02410733) that demonstrated BNT111’s favorable safety profile in 115 patients with unresectable melanoma that had prior immune checkpoint inhibitor therapy. In addition, the experimental vaccine generated durable responses, as a single agent and in combination with a PD-1 based checkpoint immunotherapy. “The results, published in the medical journal Nature, give us confidence in the scientific merit of expanding study of BNT111 into a wider patient population,” says Dr. Daud.

Learn more about the BNT111-01 Clinical Trial

Neoadjuvant Outperforms Adjuvant Therapy for Patients with Stage 3 & 4 Melanoma:

Results from a Phase 2 clinical trial of 314 patients (NCT03698019), led by MRA-funded investigator Dr. Sapna Patel (MD Anderson Cancer Center), showed that Keytruda delivered prior to surgery (what is called neoadjuvant therapy) led to better event-free survival (EFS) than the same medication delivered after surgery (what is called adjuvant therapy).

In this study, EFS was measured by the absence of:

  • melanoma progression or toxicity that prevented a patient from having surgery,
  • adjuvant therapy not initiated within 84 days of surgery,
  • postoperative relapse or recurrence of melanoma, or
  • death due to any cause. 

At two years, patients treated with Keytruda before surgery had a 23% higher EFS than those treated with Keytruda following surgery (72% versus 49%). In addition, rates of side effects were similar among both groups of patients.

“It's not just what you give, it's when you give it. The S1801 study demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes,” said Dr. Patel.

The findings are notable because neoadjuvant therapy is not FDA approved and is not regularly used outside of a clinical trial. However, based on these findings, “patients with high-risk melanoma should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the antitumor T cells are intact,” says Dr. Patel.

TIL Therapy Beats Yervoy for Patients with Advanced Melanoma:

Results from a Phase 3 clinical trial (NCT02278887) of 168 patients with advanced melanoma, led by a team of investigators in the Netherlands, showed that patients treated with TIL Therapy (explained in the next paragraph) had better outcomes than those treated with an single-agent immunotherapy drug Yervoy (ipilimumab).

TILs, or tumor-infiltrating lymphocytes, are the white blood cells that have successfully fought their way into a tumor. TIL therapy works by harvesting TILs from a patient’s tumor, expanding their numbers greatly in a lab, and then administering these lab-grown TILs back into the patient’s body. These infused cells, already primed to successfully swarm the cancer, are then further activated with high-dose interleukin-2 (IL-2).

In the study, published December 8 in the New England Journal of Medicine, patients were divided between both treatments. Patients who received TIL therapy had a 50% reduction in disease progression and death, compared to those who were treated with ipilimumab.

While neither therapy worked in all patients, about 20% of the patients treated with TIL therapy had a complete remission (meaning all of their tumors disappeared) compared to only 7% of those treated with ipilimumab. Patients who achieve a complete remission go on to have an excellent prognosis and an estimated 80% may be fully ‘cured’ of melanoma.

“The TIL trial has shown that cell therapy using the patient’s own immune cells is an extremely powerful immunotherapy for metastatic melanoma, and that this therapy still offers a high chance of improvement, even if other immunotherapies fail,” said Dr. John Haanen who led the clinical trial.

The findings are notable because this is the first Phase 3 trial that directly compared patients treated with TIL therapy against a checkpoint immunotherapy (which is considered standard of care). It also foreshadows some of the results researchers hope to see in the clinical trials by Iovance Biotherapeutics who is working to receive FDA approval for a commercialized version of TIL therapy in 2023.

Now Recruiting: ARTISTRY-6 Trial for Patients with Advanced Cutaneous or Mucosal Melanoma

Despite improved outcomes for melanoma patients with the introduction of checkpoint inhibitors (CPIs), roughly 50% of patients do not respond. A subset of responders ultimately progress and have limited treatment options, underscoring a high unmet need for these patients. Patients with mucosal melanoma have lower response rates to all available treatments compared to cutaneous melanoma.

Nemvaleukin alfa (nemvaleukin, ALKS 4230) is an investigational drug currently being studied in clinical trials. The study drug nemvaleukin is a modified molecule that binds to a protein known as interleukin-2 receptor and was designed to stimulate the body’s immune system with the goal of fighting certain types of cancers.    

ARTISTRY-6 (NCT04830124) is an ongoing phase 2, global, multicenter, open-label cohort study of nemvaleukin alfa monotherapy administered subcutaneously in patients with advanced cutaneous melanoma or intravenously in patients with advanced mucosal or cutaneous melanoma who have previously received anti-PD-(L)1 therapy. It is a research study for adult patients with advanced cutaneous melanoma or advanced mucosal melanoma that is inoperable or has spread, who have received prior treatment with an anti-programmed death-ligand 1 (anti-PD(L)1) therapy. 

“Metastatic mucosal melanoma, though not as common as skin melanoma, tends to be very high-risk disease. Clinical trial ARTISTRY-6 is attempting to face this unmet need since there are no approved therapies for mucosal melanoma. Patient participation in trials is crucial in the mucosal melanoma space”, said trial investigator Dr. Inderjit Mehmi, a medical oncologist at The Angeles Clinic and Research Institute in Los Angeles.

The study is enrolling participants in 3 different treatment groups based on disease type and the way the drug is administered.

Your doctor can determine if you might be eligible to participate in this study if you:

  • Are 18 years of age or older 
  • Have a diagnosis of advanced cutaneous melanoma or advanced mucosal melanoma that is inoperable or has spread
  • Have received prior treatment with an anti-PD(L)1 with or without an anti-CTLA4 drug, and no more than one other prior treatment for your cancer (e.g., targeted therapy, chemotherapy)
  • Have not received similar medications in the past

[Additional criteria apply]

Learn more about the ARTISTRY-6 trial

Looking for more information about melanoma clinical trials?

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