Cemiplimab Offers Hope in Metastatic CSCC

Danny Rischin, MD, MBBS, FRACP

If approved by the FDA, the PD-1 inhibitor cemiplimab may become a standard of care for select patients with metastatic and locally advanced cutaneous squamous cell carcinoma (CSCC), said Danny Rischin, MD, MBBS, FRACP, as there are currently no available agents in the landscape.

In April 2018, cemiplimab was granted a priority review by the FDA for the treatment of patients with metastatic CSCC and locally advanced CSCC who are not eligible for surgery. The priority review was based on phase I/II findings from the EMPOWER-CSCC 1 study (NCT02760498), which showed an overall response rate (ORR) of 46.3% in patients with advanced CSCC.¹ In data from a phase II study presented at the 2018 ASCO Annual Meeting and published in the New England Journal of Medicine, cemiplimab induced an ORR of 47.5% in patients with metastatic CSCC.^2,3

Also in the phase II study presented at ASCO, 28 of 59 patients had a response at a median follow-up of 7.9 months, including 4 (6.8%) partial responses and 24 (40.7%) complete responses. Of the 28 responders, 57% had responses over 6 months, and 82% had an ongoing response and continued to receive cemiplimab. The FDA is scheduled to make its decision on the cemiplimab application by October 28, 2018.

“These patients often have advanced disease with limited treatment options, and are often elderly with comorbidities,” said Rischin. “Some patients on the trial were only estimated to live for a few months, and are back to living normal lives at nearly 2 years now. It’s quite remarkable compared with the options previously.”

OncLive: Can you share the background of this study?

What is the design of the study?

What was the activity reported with cemiplimab?

In an interview with OncLive^®, Rischin, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, discussed the potential for cemiplimab as a novel PD-1 inhibitor for patients with metastatic and locally advanced CSCC.Rischin: There are no approved agents for metastatic CSCC. CSCC is a common disease, but there is a group of patients who progress after standard treatment of surgery, and up to now, there have not been any treatments for these patients. There are a couple of features of CSCC that led us to believe that it might be particularly responsive to immunotherapy. This tumor has one of the highest tumor mutational burdens and it is associated with immunosuppression. These 2 features have led us to believe immune checkpoint inhibitors were worth exploring. That was the background hypothesis that led to the phase II study.This was a single-arm, phase II study for patients with metastatic CSCC with distant metastases or with metastases to lymph nodes that were no longer amenable to any curative surgery or radiotherapy. The eligibility was restricted to immune-competent patients, so those on immunosuppressive therapy, with chronic lymphocytic leukemia, or transplant recipients were eligible. We enrolled 59 patients on this trial. Typical for a CSCC population, they were elderly with a median age of 71—in fact, the oldest patient on the trial was 93. Most of these patients had been heavily pretreated; 85% had previously received radiotherapy and 56% had previous systemic therapy of some kind.The primary objective was to determine the response rate, which was evaluated using RECIST v1.1 criteria and independent central review. The ORR was 47.5%, so just under half of patients had a response. We also found that more than 60% of patients had what we call durable disease control—so either a response or lack of progression for over 105 days. A large proportion of patients derived significant benefit.

Can you discuss the tolerability of this agent?

What are the next steps following these findings?

The other thing that was striking about these responses is that they were rapid and appeared to be durable, with the caveat of a relatively short duration. A very high proportion of patients, about 56%, remain on treatment. Of the 28 who responded, only 3 have subsequently progressed. This is very encouraging, both in terms of the level of activity and the durability of those responses.Bearing in mind that this is an elderly population, it was well tolerated. The toxicity profile was very similar to what has been seen with other anti—PD-1 drugs in other trials. There were no new toxicity signals at all; there were only 3 patients that had to stop treatment due to adverse events.The trial had multiple cohorts. We are waiting for the results from the additional cohort of locally advanced patients to mature. The drug itself is under priority review with the FDA. It is also being reviewed by the European Medicines Agency. One would expect that it would gain approval and become the standard of care in a disease for which there are no approved agents and no effective treatment options.

It is also likely that beyond treatment of these patients with recurrent or metastatic disease, an approval could provide the opportunity to look at new treatment paradigms for patients with advanced CSCC. We will explore that in future trials of earlier stages of disease.

Although the large percentage of patients respond, there are a group of patients who did not. Translational studies are being incorporated into these trials and may give us some clues about other combinations with cemiplimab that may increase the response rate, or may work in patients who do not respond to single agents.

References

1. Papadopoulos KP, Owonikoko TK, Johnson ML, et al. REGN2810: A fully human anti-PD-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study. J Clin Oncol. 2017;35(suppl; abstr 9503).
2. Rischin CD, Migden MR, Chang A, et al. Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC). J Clin Oncol. 2018;36(suppl; abstr 9519).
3. Migden MR, Rischin CD, Schmults A, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379:341-351. doi: 10.1056/NEJMoa1805131.