High-risk patients with cutaneous squamous cell carcinoma (CSCC) have an unmet need with regard to systemic adjuvant medical options after the gold standard of surgery and radiotherapy to reduce the risk of locoregional advanced disease or distant metastases. The safety profile of adjuvant cemiplimab is favorable. Professor Danny Rischin (Director of the Division of Cancer Medicine and Head of the Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia presented a phase 3 trial in progress at the American Society of Clinical Oncology (ASCO) 2022 Annual meeting, which was held 3-7 June 2022, in Chicago, IL.

The C-POST trial (NCT03969004) aims to compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy.

Although the surgical cure rate for CSCC is high, some individuals have a high risk of recurrence. Radiotherapy after surgery mitigates that risk for recurrence, but local recurrence or metastases can still occur. There is currently no systemic medical adjuvant intervention for these high-risk patients. C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for patients with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative radiotherapy (minimum total dose 50Gy, within 10 weeks prior to randomization)

The study (n=412) comprises 2 stages: Part 1 (blinded), patients are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks, and the optional Part 2 (unblinded), in which patients in the placebo arm who experience disease recurrence and patients in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The primary endpoint is disease-free survival; key secondary objectives are overall survival, locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. The COVID-19 pandemic interrupted enrollment,  but it has since re-opened.

 Physician’s Weekly was able to interview Prof. Rischin while he was at ASCO.

Could you tell me a little bit about the C-POST protocol?

“Yes. The C-POST trial is a large international trial, which is testing the potential benefit of adjuvant anti-PD-1 cemiplimab in patients with high-risk cutaneous squamous cell carcinoma.

This trial has been designed for patients who are receiving standard treatment for patients with high-risk disease, which for these patients is based on the primary tumor or their nodal disease, they undergo an initial surgery followed by post-operative radiotherapy. Standard treatment currently dictates that there is no further treatment beyond surveillance. However, in this trial, patients are then randomized in a blinded fashion between cemiplimab for 12 months, or have placebo for 12 months. The trial is trying to see if there’s a difference in disease-free survival with the addition of adjuvant cemiplimab.”

What do you hope to achieve in this trial?

“The trial is still accruing. Cutaneous squamous cell carcinoma is amongst the diseases in which anti PD-1 drugs have the most activity, and there are robust response rates in the recurrent metastatic setting. Patients with the disease where there are no further surgical radiotherapy options or if they have many metastases approaches 50%, with a significant proportion of those patients having long-term survival, which now extends from the earliest trials for several years. So the activity is quite remarkable in this disease.

We are hoping that by using it in an earlier stage of disease we can see the benefit and improve outcomes so that these patients don’t relapse. So similar to melanoma, where adjuvant anti PD-1 has been shown be beneficial. we’re optimistic that this trial may show a similar benefit in this disease.”

Are there any investigational studies looking at neoadjuvant treatment with cemiplimab?

“Yes. There was a pilot study of 20 patients that came out of the MD Anderson, led by Prof. Neil Gross (NCT03565783), which showed very encouraging results with 2 cycles of neoadjuvant PD-1 inhibition [2].

It was only 20 patients, but with 2 cycles of cemiplimab, 50% of patients had a complete pathologic response and there’s been a follow-up trial of about 80 patients which was an international trial, which will be presented later this year. The results are not yet available.”

What is the tolerability of and expected safety profile for this group of patients?

“I think the toxicity profile is very similar to other anti PD-1 drugs. It is generally well tolerated, but you do have the risk that a proportion of patients have immune-related adverse events. These are usually fairly easy to manage with steroids, those 10 to 15% of patients who will develop an immune-related adverse event. While that always remains a risk, for the great majority of patients cemiplimab is well tolerated.

With C-POST, we want to get the answer. We don’t want to be left in doubt at the end of the study about whether adjuvant cemiplimab works or it doesn’t work. These high-risk patients need systemic therapy to reduce their risk, and we just hope this can offer them a good option.”

 

  1. Rischin D et al, C-POST protocol update: A phase 3, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients with high-risk cutaneous squamous cell carcinoma (CSCC). ASCO 2022 Annual Meeting, Abstract TPS9592
  2. Ferrarotto R, et al. Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck. Clin Cancer Res. 2021 Aug 15;27(16):4557-4565.