We will be presenting the preliminary results of the phase I first in human dose escalation study of this anti-CCR8 antibody denikitug in patients with advanced solid cancers.
What was the study design?
This was a large phase I first in human study with two major components to evaluate the safety and efficacy of denikitug monotherapy and denikitug combined with an anti-PD-1 inhibitor. For AACR we are presenting the data of the two monotherapy cohorts, part A and part B.
What were the key findings?
The goals for this study were to try to understand the pharmacodynamics and the immunobiological effect of denikitug, try to understand the preliminary efficacy and the safety and tolerability profile. So going one by one, we saw that denikitug was doing exactly what we were anticipating to see. It caused a robust depletion of CCR8 positive intratumoural Tregs within the tumour microenvironment and a robust expansion and infiltration by CD8 effector T-cells.
In terms of efficacy, we were very encouraged to see early signs of activity. There was an objective response rate of 8% and a disease control rate of 46% with denikitug monotherapy in this heavily pretreated and largely IO refractory population. In terms of safety denikitug monotherapy had a manageable safety profile.
What is the importance of these results?
If I have to summarise the importance of this study I would say denikitug is showing early evidence of biological and clinical activity in this first in human study with biomarker changes consistent with the intended anti-CCR8 mechanism. We saw encouraging initial anti-tumour activity in this heavily pretreated population and the safety profile was manageable.
In the context of a highly active CCR8 field and in the broader evolution of immuno-oncology, I think this data supports the continued development of denikitug monotherapy and also in combination strategies in selected tumour types.
What is the future of this programme?
This was a large phase I study. We still have data of the denikitug combined with the anti-PD-1 that we plan to present in a future conference. There are two large global phase II studies that are under development, initiating soon, one in microsatellite stable colorectal cancer combining denikitug with anti-PD-1 inhibitor and standard chemotherapy and another phase II trial in gastric cancer or gastric and gastro-oesophageal junction combining denikitug plus anti-PD-1 inhibitor and standard chemotherapy.
