Editor's Note: Malignant melanocytes can appear in various tissues throughout the body, most commonly in the skin and mucous membranes, and are highly aggressive. With continuous advancements in targeted therapy, immunotherapy, and biological therapy, even advanced melanoma can, in many cases, be managed as a chronic disease. Looking back at 2024, what were the key research developments and treatment strategies in systemic therapy for melanoma? Oncology Frontier invited Dr. Jun Guo, Vice President of the Chinese Society of Clinical Oncology (CSCO) and professor at Peking University Cancer Hospital, to provide an expert review and summary. From Professor Guo’s annual analysis, it is evident that numerous novel treatment strategies have already begun or are poised to impact clinical practice, including some pioneering approaches originating from China.

Oncology Frontier: Melanoma has long been considered a “testing ground” for innovative therapies. Looking back at 2024, multiple novel drugs were approved or had their indications expanded both domestically and internationally. What does this reflect about the trends in melanoma treatment innovation?

Dr. Jun Guo: In December 2024, former U.S. President Jimmy Carter passed away. Beyond witnessing the establishment of U.S.-China diplomatic relations, President Carter also lived through the emergence of the “immunotherapy era.” A decade ago, he received PD-1 immune checkpoint inhibitor therapy for melanoma with liver metastases, and this treatment helped him live to the age of 100. The impact of melanoma immunotherapy, often referred to as the “Carter Effect,” is comparable to the influence of Angelina Jolie’s advocacy for breast cancer genetic testing. Both the general public and pharmaceutical companies have been significantly motivated by the “Carter Effect.”

Over the past decade, melanoma drug therapy has continued to evolve, moving from targeted therapy and immunotherapy to oncolytic virus therapy, tumor-infiltrating lymphocyte (TIL) therapy, and chimeric antigen receptor T-cell (CAR-T) therapy. In 2024, several novel therapies were approved worldwide. In February, the U.S. FDA granted accelerated approval for Lifileucel, the world’s first TIL therapy, for advanced melanoma patients who had failed PD-1 therapy. In September, the FDA also granted IBI363 a Fast Track designation for treating advanced melanoma. IBI363 is a novel bispecific antibody fusion protein targeting PD-1 and IL-2α.

In China, in March 2024, the National Medical Products Administration (NMPA) approved Trametinib for NRAS-mutant advanced melanoma patients who had failed PD-1/PD-L1 therapy. This is the world’s first and only MEK inhibitor approved for this indication. The approval was primarily based on a Phase II study published in European Journal of Cancer in May 2024 by a team from Peking University Cancer Hospital, reporting an objective response rate (ORR) of 35.8% for Trametinib in advanced melanoma, with an ORR of 40.6% in patients previously treated with immunotherapy. Furthermore, due to the success of the MELATORCH trial, a Phase III study evaluating Toripalimab as first-line treatment for advanced melanoma, the NMPA recently converted its conditional approval for second-line treatment into full approval.

These approvals in 2024 highlight the diversity of novel melanoma therapies, ranging from new immune-based treatments such as TIL therapy and bispecific antibodies to China’s pioneering NRAS-targeted therapy, marking a new era of diverse therapeutic options in melanoma treatment.

Oncology Frontier: Major oncology conferences such as ASCO, ESMO, and CSCO in 2024 showcased significant advances in systemic therapy for advanced melanoma. What were the key clinical developments and areas of focus?

Dr. Jun Guo: A decade ago, the global medical community established immunotherapy as the standard treatment for melanoma. President Carter’s long survival after immunotherapy is not an isolated case—clinical trials and real-world data confirm that many advanced melanoma patients achieve long-term survival.

At the 2024 ESMO Congress, long-term follow-up data from the CheckMate-067 and KEYNOTE-006 Phase III trials were presented, tracking patients who received first-line immunotherapy for ten years.

In CheckMate-067, the nivolumab + ipilimumab (NIVO + IPI) combination (HR 0.53, 95% CI: 0.44-0.65) and nivolumab monotherapy (HR 0.63, 95% CI: 0.52-0.76) both significantly improved overall survival (OS) compared to ipilimumab monotherapy. The 10-year OS rates were 43%, 37%, and 19%, respectively.

In KEYNOTE-006, pembrolizumab demonstrated a superior OS compared to ipilimumab (HR 0.71, 95% CI: 0.60-0.85), with 10-year OS rates of 34% and 23.6%, respectively.

China also introduced its first-line immunotherapy regimen. At the 2024 CSCO conference, we presented results from the MELATORCH trial, a Phase III study comparing Toripalimab vs. Dacarbazine. Toripalimab significantly improved progression-free survival (PFS) (2.3 vs. 2.1 months, HR 0.708; 95% CI: 0.526-0.954, P=0.0209), while also showing a trend towards OS benefit (15.1 vs. 9.4 months, HR 0.680, 95% CI: 0.486-0.951).

Another major topic in 2024 was sequencing targeted and immunotherapy for BRAF V600-mutant melanoma. Several new trials—EBIN and ImmunoCobiVem—were presented. The EBIN trial, presented at ASCO 2024, compared sequential targeted therapy + immunotherapy vs. immunotherapy alone but found no significant advantage for sequential therapy (HR 0.87, 95% CI: 0.67-1.12, P=0.360). The ImmunoCobiVem trial, reported at ESMO 2024, tested three months of targeted therapy (lead-in phase) before switching to immunotherapy. While targeted therapy improved initial PFS (13 vs. 5.9 months, HR 0.61), there was no significant difference in long-term survival (PFS2) between the groups (12.6 vs. 14.6 months, HR 1.29, P=0.41).

Oncology Frontier: Neoadjuvant therapy for melanoma remains an emerging field with no established standard. In 2024, your team achieved a breakthrough in this area. Could you share some insights?

Dr. Jun Guo: Melanoma is a highly immunogenic tumor, and neoadjuvant immunotherapy has delivered promising results in recent years.

The NADINA trial, presented at ASCO 2024 and published in NEJM, found that nivolumab + ipilimumab neoadjuvant therapy achieved a pathological complete response (pCR) rate of 47.2% and significantly improved 1-year event-free survival (EFS) by 26.5% (83.7% vs. 57.2%, HR 0.32, P<0.0001).

Most Western studies focus on cutaneous melanoma, but our team led a Phase Ib trial published in Nature STTT in November 2024, evaluating an oncolytic virus + Toripalimab for high-risk acral melanoma. The study achieved a pCR rate of 77.8%, with 1-year RFS and EFS rates of 85.2% and 83%, respectively, making it the first published neoadjuvant study for acral melanoma.

Oncology Frontier: Looking ahead, how can Chinese researchers continue making internationally impactful contributions in melanoma research?

Dr. Jun Guo: We must leverage the unique molecular and immune characteristics of melanoma in China to develop precision medicine approaches, drive mechanistic research, foster multidisciplinary collaboration, and accelerate new drug development. With continued efforts, we will contribute more China-specific treatment strategies to the global melanoma field.