Cosibelimab Shows Promising Efficacy and Safety in Cutaneous CSCC

According to Jason J. Luke, MD, FACP, director of the Immunotherapy and Drug Development Center, associate director of Clinical Research, and associate professor of medicine at the University of Pittsburgh and University of Pittsburgh Hillman Cancer Center, and melanoma editorial board member of ONCOLOGY®, results from a phase 1 CK-301-101 trial (NCT03212404) seem to support the use of cosibelimab (Unloxcyt) in the treatment of patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC).

CancerNetwork® spoke with Luke prior to the FDA approval of cosibelimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiotherapy.¹ He reiterated that the data from the trial was promising and enters cosibelimab into the conversation of treatment alongside cemiplimab (Libtayo) and pembrolizumab (Keytruda). Luke rejected criticisms that the fact that the supporting data comes from a phase 1 trial weakens the drug’s case because of how difficult it can be to enroll patients who have this disease.

Of the supporting data, Luke specifically cited a strong overall response rate (ORR). In the trial, the ORR was 47% (95% CI, 36%-59%). For patients with metastatic disease and 48% (95% CI, 30%-67%) for those with locally advanced disease. The median duration of response was not reached (range, 1.4+ to 34.1+ months) in the metastatic group and 17.7 months (range, 3.7+ to 17.7) in the locally advanced group.

On safety, Luke stated that the AE profile appears similar to other in-class agents, and he also affirmed that he would have no worries about treating any specific patient subgroups outside of what was already known. Regarding adverse effects, the most common were fatigue (26.9%), rash (16.7%), and anemia (15.4%).²

Transcript:

The data looks quite promising in terms of the overall response rate that we would see. I don’t think it should be a big criticism that the data came from a phase 1 trial. This is a treatment population that, while common in general oncology practice, is very difficult to accrue patients to because the patients who have this disease very commonly have comorbidities or other medical problems that make them difficult clinical trial candidates. For all the reasons that we have standardized clinical trials for data interpretation…this is a population where it’s not so easy to accrue hundreds of [patients], for example. Therefore, we need to do what we can to generate high-quality evidence, but [also] realize that we’re not going to have huge studies in this disease setting.

If you look at the approvals of cemiplimab and pembrolizumab, they come from data series that are slightly larger but approximately the same size. What we know about those drugs is we have a much longer runway, including in other cancers, for their effectiveness. Here, this drug has been developed, specifically in cutaneous squamous cells, so we don’t have that other comparison point. I don’t criticize these data. I do want to see more data, of course, but I think these data are promising, and they suggest this is an active agent.

This is one of those questions [that’s] a little bit hard to tell given the modest number of people we have to look at so far. My take on it has been that we see the same adverse effect profile that we would expect with the other in-class agents. I haven’t seen anything that makes me especially worried that there would be a group of patients I wouldn’t want to treat outside of what we already understand about autoimmunity and the frailty of patients… That just emphasizes this treatment population tends to be older folks, and their ability to tolerate a lot of AEs is always a question mark. We have to be very careful about that. I haven’t seen anything specifically with cosibelimab that would make me worried that there’s a problem.

References

1. FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. News release. FDA. December 13, 2024. Accessed December 16, 2024. https://tinyurl.com/2wdtzrxa
2. Clingan P, Ladwa R, Brungs D, et al. Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma. J Immunother Cancer. 2023;11(10):e007637. doi:10.1136/jitc-2023-007637