2024 Breakthroughs in Skin Cancer

Image Credit: © InsideCreativeHouse - stock.adobe.com

In 2024, significant advancements reshaped skin cancer treatment. From FDA approvals of new therapies to updated clinical guidelines, the latest breakthroughs aim to improve outcomes for patients facing melanoma and nonmelanoma cancers. With new insights into therapies such as lifileucel and IBI363, updated protocols for radiation in basal and squamous cell carcinoma, and innovative immunotherapy combinations, these developments highlight the strides made in combating skin cancer’s toughest challenges.

Lifileucel Receives FDA Accelerated Approval for Advanced Melanoma

Iovance Biotherapeutics announced in February 2024 that the FDA approved lifileucel (Amtagvi) suspension for intravenous infusion for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. Lifileucel’sindication is FDA approved under an accelerated approval based on overall response rate and duration of response. Iovance is also conducting TILVANCE-301, a phase 3 trial to confirm the clinical benefit of lifileucel. The FDA accelerated approval of lifileucel is based on safety and efficacy data from the C-144-01 clinical trial.¹

IBI363 Monotherapy Granted Fast Track Designation in US for Advanced Melanoma

The US FDA granted fast track designation in September 2024 to Innovent Biologics’ IBI363, a PD-1/IL-2α bispecific antibody fusion protein therapy, for patients with unresectable, locally advanced or metastatic melanoma. The treatment is intended for individuals whose disease has progressed despite intervention with at least 1 prior PD-1/L1 inhibitor and systemic therapy. It is not intended for individuals with choroidal melanoma. Of 37 patients given IBI363 at 1 mg/kg, 11 demonstrated objective responses, with 1 complete response and 10 partial responses recorded. The overall response rate was 29.7% and the disease control rate was 73.0%.²

New Clinical Guidelines for Nonmelanoma Skin Cancer Published by Dermatology Association of Radiation Therapy

The Dermatology Association of Radiation Therapy (DART) recently announced the publication of new clinical guidelines for the treatment of nonmelanoma skin cancers basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The guidelines were developed collaboratively by DART’s education and research committees. At the core of the new guidelines is the emphasis on the use of image-guided superficial radiation therapy (IGSRT). This technique combines high-resolution dermal ultrasound imaging with superficial radiation therapy, allowing for precise targeting of cancerous tissues. The guidelines offer comprehensive criteria for the use of IGSRT in treating both BCC and SCC, covering aspects such as diagnosis and staging, indications and contraindications, treatment protocols, and follow-up procedures.³

FDA Updates PDUFA Date of Subcutaneous Nivolumab

Bristol Myers Squibb announced in May 2024 that the US FDA reassigned the previously determined Prescription Drug User Fee Act (PDUFA) action date of the biologics license application (BLA) for the subcutaneous formulation of nivolumab (Opdivo) to December 29, 2024. The original PDUFA date was February 28, 2025. The subcutaneous formulation of nivolumab is co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20) for all previously approved adult, solid tumor nivolumab indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy) combination therapy, or in combination with chemotherapy or cabozantinib. The acceptance of Bristol Myers Squibb’s BLA is based on data from the phase 3 CheckMate-67T study where subcutaneous nivolumab demonstrated noninferiority of Cavgd28 (time-averaged nivolumab serum concentration over 28 days) and Cminss (trough serum concentration at steady state), the study’s co–primary end points, compared with intravenous nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma who had received prior systemic therapy.⁴

Moderna and Merck Announce 3-Year Data for mRNA-4157 Combined With Pembrolizumab for High-Risk Stage III/IV Melanoma

Moderna and Merck announced new results in June 2024 from a planned analysis from the phase 2b randomized KEYNOTE-942 clinical trial (NCT03897881) evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy, in combination with pembrolizumab (Keytruda), Merck’s anti–PD-1 therapy, in patients with resected high-risk stage III/IV melanoma following complete resection (n = 157). After a median follow-up of 3 years (34.9 months), adjuvant treatment with mRNA-4157 in combination with pembrolizumab continued to show a clinically meaningful and durable improvement in the primary end point of recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR, 0.510; 95% CI, 0.288-0.906), compared with pembrolizumab as monotherapy. The combination of mRNA-4157 and pembrolizumab also demonstrated a meaningful improvement in one of the key secondary end points of distant metastasis-free survival compared with pembrolizumab as monotherapy, therefore reducing the risk of developing distant metastasis or death by 62% (HR, 0.384; 95% CI, 0.172-0.858).⁵

References

1. Iovance’s AMTAGVI (lifileucel) receives U.S. FDA accelerated approval for advanced melanoma. News release. Iovance Biotherapeutics. February 16, 2024. Accessed November 5, 2024. https://ir.iovance.com/news-releases/news-release-details/iovances-amtagvitm-lifileucel-receives-us-fda-accelerated
2. Innovent receives fast track designation from the U.S. FDA for IBI363 (PD-1/IL-2αbispecific antibody fusion protein) as monotherapy for advanced melanoma. News release. Innovent Biologics. September 3, 2024. Accessed November 5, 2024. https://www.prnewswire.com/news-releases/innovent-receives-fast-track-designation-from-the-us-fda-for-ibi363-pd-1il-2-bispecific-antibody-fusion-protein-as-monotherapy-for-advanced-melanoma-302236636.html
3. Dermatology Association of Radiation Therapy publishes new clinical guidelines for the treatment of nonmelanoma skin cancer. News release. Dermatology Association of Radiation Therapy. July 22, 2024. Accessed November 5, 2024. https://www.prnewswire.com/news-releases/dermatology-association-of-radiation-therapy-publishes-new-clinical-guidelines-for-the-treatment-of-nonmelanoma-skin-cancer-302202264.html
4. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 21, 2024. Accessed November 5, 2024. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx
5. Moderna & Merck announce 3-year data for mRNA-4157 (V940) in combination with Keytruda (pembrolizumab) demonstrated sustained improvement in recurrence-free survival & distant metastasis-free survival versus Keytruda in patients with high-risk stage III/IV melanoma following complete resection. News release. Merck. June 3, 2024. Accessed November 5, 2024. https://www.merck.com/news/moderna-merck-announce-3-year-data-for-mrna-4157-v940-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-recurrence-free-survival-distant-metastasis-free-su/