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EHA 2026 | Insights into the KEYFORM-008 trial: favezelimab plus pembrolizumab versus chemotherapy for HL
Guilherme Perini, MD, Hospital Israelita Albert Einstein, São Paulo, Brazil, presents findings from the Phase II KEYFORM-008 (NCT05508867) trial comparing the combination of favezelimab and pembrolizumab with standard chemotherapy in patients with relapsed/refractory classical Hodgkin lymphoma (HL). Dr Perini notes that, despite favorable efficacy outcomes observed in the favezelimab plus pembrolizumab group, which suggest that the dual blockade of anti-LAG-3 and PD-1 can improve responses, implementation in clinical practice remains challenging. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
The KEYFORM-008 was one trial looking at what we call the post-PD-1 scenario. We know that these patients with Hodgkin’s lymphoma that were treated with a checkpoint inhibitor such as pembrolizumab or nivolumab, especially in monotherapy in the relapsed/refractory setting, they will eventually progress on the therapy. And we don’t know yet how to treat these patients. So the idea was to test a combination of pembrolizumab with favelezumab, that’s an anti-LAG3 checkpoint inhibitor, in these patients as a way to regain sensitivity to PD-1 blockade...
The KEYFORM-008 was one trial looking at what we call the post-PD-1 scenario. We know that these patients with Hodgkin’s lymphoma that were treated with a checkpoint inhibitor such as pembrolizumab or nivolumab, especially in monotherapy in the relapsed/refractory setting, they will eventually progress on the therapy. And we don’t know yet how to treat these patients. So the idea was to test a combination of pembrolizumab with favelezumab, that’s an anti-LAG3 checkpoint inhibitor, in these patients as a way to regain sensitivity to PD-1 blockade. And it was a randomized trial against the investigator’s choice of chemotherapy. So the study was positive. The PFS was better with Pembrolizumab and favelezumab than with chemotherapy. The disease control rate was pretty similar, although we did see more complete responses in the chemotherapy arm. But these responses are very short-lived. As soon as the patient stops chemotherapy, the patient relapses again. So it’s a proof of concept. We now know that we can, we might regain sensitivity to PD-1 blockade, but unfortunately due to a business decision from the sponsor, the FAVE program was discontinued. So it’s a proof of concept, but I don’t see this becoming part of reality right now. The results are good. There’s a proof of concept that these new checkpoint inhibitors work. They are able to regain the sensitivity to PD-1. But I still think that this scenario of the post-PD-1 in Hodgkin’s lymphoma remains very, very challenging. Of course, when we’re using it in first-line therapy, the number of patients that will eventually fail therapy becomes lower and lower. We’re curing way more patients than we used to cure with chemotherapy alone or even with ADC combinations. But I think that this patient is still a standard for these patients. What we usually do for these patients today, I mean, we may try chemotherapy, we may try allogenic transplant, but I really think that biologically, trying to regain PD-1 sensitivity is really, really important.
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