Dr Moreno on the Pharmacodynamics of CLN-619 in Advanced Solid Tumors

The [levels of] CD56-positive and NKG2D-positive cells were higher [in responders] with more infiltration after treatment [vs] before treatment compared with non-responders. In addition, we saw that [levels of] regulatory T cells were going down [in responders]. That favors the [proposed] mechanism of action [of CLN-619] in relationship with the response of patients."

Victor Moreno, MD, PhD, medical oncologist, director, Clinical Research, START Madrid-Fundación Jimenez Diaz (FJD), discusses insights into the pharmacodynamic data for CLN-619, a novel humanized IgG1 antibody designed to bind to MICA and MICB, in patients with advanced solid tumors. Findings were presented by Moreno and colleagues during the 2024 SITC Annual Meeting.

This analysis stemmed from patients treated during a phase 1 trial (NCT05117476), which is evaluating CLN-619 as monotherapy and in combination with pembrolizumab (Keytruda) in patients with advanced solid tumors. Prior data showed that both the monotherapy and combination regimens demonstrated safety and elicited objective responses.

The pharmacodynamic analysis involved the collection of paired biopsies before and after treatment, which allowed investigators to assess immune response activation in the peripheral blood and the tumor microenvironment, Moreno begins. This analysis included 12 paired biopsies from patients.

Peripheral blood analyses showed an increase in CD56-positive and natural killer G2D (NKG2D)–positive cells, Moreno says, adding that T-cell counts were also elevated. He notes that these findings help support the proposed mechanism of action for CLN-619.

In tumor biopsies, post-treatment samples revealed a greater infiltration of NK cells in patients who responded to therapy compared with non-responders, Moreno continues. Notably, these responders demonstrated higher levels of CD56-positive and NKG2D-positive cells within the tumor after treatment vs baseline. Additionally, investigators observed a decrease in regulatory T cells in the tumor microenvironment following CLN-619 treatment, Moreno notes.

Collectively, these data further support the mechanism of action of CLN-619 in relation to responses observed in patients, Moreno concludes.