Cemiplimab Offers Hope in Metastatic CSCC


Danny Rischin, MD, MBBS, discusses the phase II activity with cemiplimab as a novel PD-1 inhibitor for patients with metastatic and locally advanced CSCC.

Danny Rischin, MD, MBBS

Danny Rischin, MD, MBBS

With the FDA approval of cemiplimab (Libtayo) for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or those with locally advanced CSCC who are not candidates for curative surgery or curative radiation, there is finally a standard of care available.

The August 2018 approval is based on a combined analysis of data from the phase II EMPOWER-CSCC-1 (Study 1540) trial and 2 advanced CSCC expansion cohorts from a phase I trial (Study 1423). The combined analysis included 75 patients with metastatic CSCC and 33 patients with locally advanced CSCC.

At a median follow-up of 8.9 months and across the entire population, the overall response rate (ORR) was 47.5% (95% CI, 38%-57%); the complete response rate was 4% and the partial response rate was 44%. The duration of response (DOR) ranged from 1 month to more than 15 months, and 61% of patients had a duration of response ≥6 months.

Moreover, in data from a phase II study presented at the 2018 American Society of Clinical Oncology Annual Meeting and published in theNew England Journal of Medicine, cemiplimab induced an ORR of 47.5% in patients with metastatic CSCC.1,2

Follow-up results from an open-label, multicenter, ascending dose-escalation phase I trial (NCT02383212) of cemiplimab in this patient population continued to show efficacy, with an ORR of 50.0% (95% CI, 29.9%-70.1%) and a disease control rate of 57.7% (95% CI, 36.9%-76.6%).3Rapid, deep, and durable target lesion reductions were reported in the majority of patients who underwent at least 1 tumor assessment while receiving treatment. At the time of data cutoff, the median DOR had not been reached.

In an interview withTargeted Oncology, Danny Rischin, MD, MBBS, Director, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, discussed the phase II activity with cemiplimab as a novel PD-1 inhibitor for patients with metastatic and locally advanced CSCC.

Targeted Oncology: Could you share the background of the phase II study?

Rischin: CSCC is a common disease, but there is a group of patients who progress after standard treatments of surgery and radiotherapy, and up to now, there have not been any treatments for these patients. A couple of features of CSCC led us to believe that it might be particularly responsive to immunotherapy and that immune checkpoint inhibitors were worth exploring: This tumor has one of the highest tumor mutational burdens, and it is associated with immunosuppression. That was the background hypothesis that led to the phase II study.

Targeted Oncology: What is the study design?

Rischin: 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 transplant recipients, patients with chronic lymphocytic leukemia, and those on immunosuppressive therapy were ineligible. 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.

Targeted Oncology: What was the activity reported with cemiplimab?

Rischin: 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 defined as durable disease control—so either a response or lack of progression for more than 105 days. A large proportion of patients derived significant benefit.

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 of follow-up. A very high proportion of patients, about 56%, remain on treatment. Of the 28 who responded, only 3 had subsequently progressed at the time of the data cutoff. This is very encouraging, both in terms of the level of activity and the durability of those responses.

Targeted Oncology: Can you discuss the tolerability of this agent?

Rischin: 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 who had to stop treatment due to adverse events.

Targeted Oncology: What are the next steps following these findings?

Rischin: The trial had multiple cohorts. We are waiting for the results from the additional cohort of locally advanced patients to mature. [Cemiplimab] is being reviewed by the European Medicines Agency. One would expect that it would gain approval and also become the standard of care in Europe for a disease for which there were previously 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 targeting patients with earlier stages of disease.

Although a large percentage of patients responded, 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.


  1. Rischin D, 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(15 suppl; abstr 9519). doi:10.1200/JCO.2018.36.15_suppl.9519.
  2. Migden MR, Rischin CD, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma.N Engl J Med. 2018;379(4):341-351. doi: 10.1056/NEJMoa1805131.
  3. Owonlkoko TK, Papadopoulos KP, Gil-Martin M, et al. Phase 1 study of cemiplimab, a human monoclonal anti-PD-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): longer follow-up efficacy and safety data [published online October 23, 2018].Ann Oncol. doi:10.1093/annonc/mdy289.048.
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