A new phase 3 study has begun enrolling patients with high-risk, locally advanced cutaneous squamous cell carcinoma (cSCC) to evaluate the curative potential of adjuvant pembrolizumab. Cleveland Clinic oncologist Jessica Geiger, MD, introduced the study — called KEYNOTE-630 (NCT03833167) — in a presentation at the 2019 American Society of Clinical Oncology Annual Meeting.
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“This is one of the first randomized, double-blind, placebo-controlled phase 3 trials incorporating immunotherapy in cSCC in the curative setting,” says Dr. Geiger, co-principal investigator. “The results could be practice-changing.”
Not your typical squamous cell carcinoma
The second most common non-melanoma skin cancer, cSCC is usually treated with local therapies by dermatologists. However, aggressive cSCC requires more extensive resection and radiotherapy. Medical and radiation oncologists treat this aggressive disease, which often appears on the head and neck area, similarly to head and neck squamous cell carcinoma (HNSCC).
“CSCC does not behave like traditional mucosal head and neck squamous cell carcinomas,” says Dr. Geiger. “Though the way we treat them is similar to other head and neck cancers — resection, followed by radiation and potentially systemic therapy — cSCC is a different disease with a different biology, and the patient population tends to be different than mucosal HNSCC.”
Until recently, there were no systemic therapies approved for cSCC by the U.S. Food and Drug Administration (FDA). That changed in 2018 when PD-1 inhibitor cemiplimab was approved to treat metastatic and other advanced cSCC in patients who were not candidates for resection or radiation.
“We know immunotherapy works in cSCC,” says Dr. Geiger. “But can it be used with resection and radiation to prevent recurrence or metastasis? That’s what KEYNOTE-630 will help us determine.”
Recurrence or metastasis occurs in 40-50% of patients with high-risk, locally advanced cSCC.
KEYNOTE-630 will study the PD-1 inhibitor pembrolizumab, already FDA-approved for a wide range of other malignancies, including HNSCC. Dr. Geiger says oncologists have been using it off-label in cSCC and have noted its effectiveness.
Eligible patients who have had surgical resection and radiotherapy for high-risk, locally advanced cSCC will receive either pembrolizumab (400 mg, intravenous, every six weeks) or placebo for up to nine cycles (about one year of therapy). They will have regular imaging to assess their response to treatment.
Recurrence-free survival will be the primary end point. Secondary end points will include overall survival, quality of life and incidence of adverse events.
Ongoing recruitment in 19 countries
Recruitment started in March 2019 and is underway in 19 countries.
“Our goal is 570 patients, so it will require multi-institutional involvement since advanced cases of cSCC are relatively rare,” says Dr. Geiger. “We look forward to collecting sufficient data that we expect will show that pembrolizumab provides a durable response in these patients.”
For more information about this trial, see clinicaltrials.gov/ct2/show/NCT03833167.
Image credit: National Cancer Institute