Ken Pienta, acting chief medical officer of Cue Biopharma, said the researchers believe that CUE-101 may lead to enhanced anti-tumor activity in combination with Merck’s powerhouse checkpoint inhibitor.
Cue Biopharma forged a clinical collaboration with Merck to combine its lead candidate CUE-101 with Merck‘s Keytruda as a first-line treatment for HPV+ recurrent/metastatic head and neck cancer.
The two companies will begin a Phase I study, dubbed KEYNOTE-A78, that will evaluate the combination treatment as a potential first-line therapy. CUE-101 is a fusion protein made up of a human leukocyte antigen complex, an HPV16 E7 peptide epitope, reduced affinity human interleukin-2 (IL-2) molecules, and an effector attenuated human immunoglobulin G (IgG1) Fc domain, according to the company. In preclinical studies, CUE-101 demonstrated selective induction and expansion of HPV16 E7-specific cytotoxic T cells. The studies also showed both in vitro and in vivo evidence supporting its potential for clinical efficacy both as a monotherapy and in combination with an anti-PD1 checkpoint inhibitor like Keytruda. Merck’s Keytruda has been approved by the U.S. Food and Drug Administration for use in the treatment of some head and neck cancers. The use of CUE-101 marks the first time disease-relevant T cells have been engaged in vivo to attack cancer, eliminating the need for ex vivo manipulation and expansion of T cells. The drug candidate is also potentially more selective and can specifically target relevant T cells without activating the broad immune system, Cue told BioSpace.
Ken Pienta, acting chief medical officer of Cue Biopharma, said the researchers believe that CUE-101 may lead to enhanced anti-tumor activity in combination with Merck’s powerhouse checkpoint inhibitor.
“Immunotherapies have revolutionized the treatment of patients with certain types of cancers. However significant unmet need remains – particularly in those individuals who do not respond or develop resistance to checkpoint therapy,” Pienta said in a statement.
KEYNOTE-A78 will be conducted in parallel with the ongoing Phase I monotherapy study of CUE-101 post-first-line treatment. Initial pharmacodynamic data from the monotherapy portion of the study are expected in the first half of this year. The early monotherapy PK data from the first two dosing cohorts demonstrates dose-related drug exposure consistent with preclinical modeling, the company said. Subsequent to the respective dose escalations, expansion cohorts evaluating CUE-101 as a monotherapy and in combination with Keytruda will be conducted at optimized dosing regimens, Cue said in its announcement.
Cue Chief Executive Officer Daniel Passeri said through the monotherapy and combination studies the company is conducting, he believes they will be able to “demonstrate the mechanistic advantages of our approach and platform for modulating disease-relevant T cells directly in the patient’s body to safely enhance efficacy over current standards of care.”
Financial terms of the collaboration were not announced.
