Reviewing the Skin Cancer Pipeline: A Look at the Last 10 Years

The US Food and Drug Administration (FDA) has approved several therapies for patients with skin cancer over the years. From innovations such as combination therapy approvals to the clearance of artificial intelligence devices, research and stamps of approval have led to significant improvements in patient care.

This Skin Cancer Awareness Month, Dermatology Times is recapping the last 10 years of news in the skin cancer drug pipeline.

November 2015: Cobimetinib is approved by the FDA

On November 10, 2015, the FDA approved Genentech's Cotellic (cobimetinib) for use with Zelboraf (vemurafenib) in treating advanced melanoma with BRAF V600E or V600K mutations. The approval was based on the phase III coBRIM study, which showed that the combination therapy significantly improved progression-free survival and overall survival compared to Zelboraf alone. Patients receiving the combination therapy had a median progression-free survival of 12.3 months versus 7.2 months with Zelboraf alone.¹

June 2018: Binimetinib is approved by the FDA

On June 27, 2018, the FDA approved the combination of encorafenib (Braftovi) and binimetinib (Mektovi) for treating patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. This approval followed results from the COLUMBUS trial, which included 577 patients. The trial demonstrated that patients receiving the combination therapy had a median progression-free survival (PFS) of 14.9 months compared to 7.3 months for those receiving vemurafenib alone. Additionally, the THxID BRAF Kit was approved as a companion diagnostic for these treatments.²

September 2018: Cemiplimab-rwlc is approved by the FDA

On September 28, 2018, the FDA approved cemiplimab-rwlc (Libtayo) for patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation. The approval was based on significant and durable objective response rates observed in two clinical trials, R2810-ONC-1423 and R2810-ONC-1540, involving patients with advanced CSCC. In these trials, the overall response rate was 47%, with some patients achieving complete or partial responses. The responses were durable, with a median response duration not reached and 61% of responses lasting six months or more.³

December 2021: Pembrolizumab is approved by the FDA

On December 3, 2021, the FDA approved pembrolizumab (Keytruda) for the adjuvant treatment of adults and children (12 years and older) with stage IIB or IIC melanoma after complete resection. The approval was based on the KEYNOTE-716 trial, a randomized, double-blind, placebo-controlled study involving patients with resected stage IIB or IIC melanoma. Participants received either pembrolizumab or a placebo every three weeks for up to a year. The primary measure of efficacy was recurrence-free survival (RFS), with results showing a significant improvement in the pembrolizumab group (hazard ratio of 0.65).⁴

October 2023: Nivolumab is approved by the FDA

On October 13, 2024, the FDA approved nivolumab (Opdivo) from Bristol Myers Squibb for the adjuvant treatment of patients with completely resected stage IIB or IIC melanoma. This decision was based on the phase 3 CheckMate -76K trial, which showed nivolumab significantly improved recurrence-free survival (RFS) compared to placebo. The safety profile was consistent with previous studies.⁵

January 2024: DermaSensor device is cleared by the FDA

The FDA approved DermaSensor, a handheld device, for detecting skin cancers such as melanoma, basal cell carcinoma, and squamous cell carcinoma. The AI-powered device is designed for use by primary care physicians and utilizes elastic scattering spectroscopy to analyze suspicious skin lesions.⁶

In a multicenter study, DermaSensor showed a sensitivity of 95.5% and specificity of 32.5%, with a positive predictive value of 16.0% and a negative predictive value of 98.1%. Earlier studies demonstrated a sensitivity of 94% for high-risk lesions and 23% specificity for low-risk lesions.⁶

February 2024: Lifileucel is granted accelerated approval by the FDA

In February, Iovance Biotherapeutics announced the accelerated FDA approval of lifileucel (Amtagvi) for treating adult patients with unresectable or metastatic melanoma who have previously been treated with a PD-1 blocking antibody, and, if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. The approval was based on the overall response rate and duration of response from the C-144-01 clinical trial.⁷

The C-144-01 trial showed a 31.5% objective response rate in 73 patients, with a median duration of response not reached at 18.6 months follow-up, and 43.5% of responses lasting over 12 months. A pooled analysis of 153 patients showed a 31.4% response rate, with 54.2% of responses lasting more than 12 months.⁷

References

1. FDA approves Genentech’s Cotellic (cobimetinib) in combination with Zelboraf (vemurafenib) in advanced melanoma. News release. Genetech. November 10, 2015. Accessed May 20, 2024. https://www.gene.com/media/press-releases/14611/2015-11-10/fda-approves-genentechs-cotellic-cobimet
2. FDA approves encorafenib and binimetinib in combination for unresectable or metastatic melanoma with BRAF mutations. News release. US FDA. Updated June 27, 2018. Accessed May 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-encorafenib-and-binimetinib-combination-unresectable-or-metastatic-melanoma-braf#:~:text=On%20June%2027%2C%202018%2C%20the,by%20an%20FDA%2Dapproved%20test
3. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. News release. US FDA. Updated January 18, 2019. Accessed May 20, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma
4. FDA approves pembrolizumab for adjuvant treatment of Stage IIB or IIC melanoma. News release. US FDA. Updated December 6, 2021. Accessed May 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-stage-iib-or-iic-melanoma
5. US Food and Drug Administration approves Bristol Myers Squibb’s nivolumab for Opdivo (nivolumab) as an adjuvant treatment for patients with completely resected stage IIB or IIC melanoma. News release. Bristol Myers Squibb. October 13, 2023. Accessed May 20, 2024. https://news.bms.com/news/corporate-financial/2023/U.S.-Food-and-Drug-Administration-Approves-Opdivonivolumab-as-Adjuvant-Treatment-for-Eligible-Patients-with-Completely-Resected-Stage-IIB-or-Stage-IIC-Melanoma1/default.aspx
6. FDA clearance granted for first AI-powered medical device to detect all three common skin cancers (melanoma, basal cell carcinoma and squamous cell carcinoma). News release. DermaSensor. January 17, 2024. Accessed May 20, 2024. https://www.dermasensor.com/fda-clearance-granted-for-first-ai-powered-medical-device-to-detect-all-three-common-skin-cancers-melanoma-basal-cell-carcinoma-and-squamous-cell-carcinoma/
7. Iovance’s AMTAGVI (lifileucel) receives US FDA accelerated approval for advanced melanoma. News release. Iovance Biotherapeutics. February 16, 2024. Accessed May 20, 2024. https://ir.iovance.com/news-releases/news-release-details/iovances-amtagvitm-lifileucel-receives-us-fda-accelerated