Novel Agent CUE-101 Shows Promise in Recurrent/Metastatic HNSCC


Treatment with CUE-101 continued to show promise for patients with head and neck squamous cell carcinoma when combined with pembrolizumab or used as a monotherapy.

Use of the novel agent CUE-101 as monotherapy and in combination with pembrolizumab (Keytruda) showed promising safety and efficacy signs in patients with recurrent/metastatic human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), according to a press release.

An open-label, 4-part, phase 1b trial (NCT03978689) showed an overall response rate (ORR) of 40% and a 70% clinical benefit rate (CBR) in the first 10 patients given the recommended phase 2 dose (RP2D) of 4 mg/kg of CUE-101 and 200 mg of pembrolizumab given every 3 weeks. Among these responses, there were 4 confirmed partial responses (cPR) and 3 durable stable disease (DSD) at 12 weeks or longer. In an expansion of the phase 1b trial, monotherapy of CUE-101 continued to show these promising responses, but data was not yet matured.

Findings were reported in a poster presentation at the Society for Immunotherapy of Cancer’s 37th Annual Meeting. These results showed that tumor reduction from baseline in 5 patients with cPRs was between 35%-69%.

“We are very encouraged with the overall response rate observed in the trial so far with CUE-101, and its potential to improve standard of care for [patients with] HPV-positive head and neck cancer,” said Christine Chung, MD, chair, department of Head and Neck-Endocrine Oncology at the Moffitt Cancer Center, and a principal investigator in the trial, in the press release. “There is an urgent need for more effective and durable treatment options with less side effects as more than half of all patients with recurrent/metastatic HNSCC given the current standard of care will experience disease progression. I look forward to following this promising CUE-101 clinical data through.”

Within the monotherapy expansion arm, there was a 42% overall CBR, 1 PR of longer than 42 weeks, and 7 patients with DSD. The median overall survival (OS) was trending greater than 12 months for patients in the 3rd line and beyond setting. However, these data are not mature at this time. Twelve patients were still alive of the cohort looking at OS who were given the RP2D. The best change in their disease was also seen in the 4 mg/kg of pembrolizumab and the CUE-101 cohort with treatment ongoing in 7 patients.

“This new data from our combination study demonstrates early evidence of complementary mechanistic activity of CUE-101 with pembrolizumab. In addition, the sustained clinical benefit rate with CUE-101 as monotherapy is very encouraging and has continued to demonstrate proof-of-concept of CUE-101 as a single agent,” said Ken Pienta, MD, acting chief medical officer of Cue Biopharma, in the press release. “Overall, the data shows the potential of CUE-101 to provide patients with an improved clinical benefit rate and with lower toxicity than current standard of care. We look forward to continuing to evaluate data from the trial in addition to defining the potential registrational trial for CUE-101, which we anticipate in mid-2023.”

In the overall study, 49 patients were given CUE-101 as a monotherapy with the 4 mg/kg cohort being expanded to 20 patients, but 17 patients were ultimately treated. Patients had a median age of 62.4 years, 10 patients had an ECOG performance status of 0, and 7 patients had a score of 1.

Nine patients had a CPS score of 1-20 and 8 patients had a CPS score of 20 or more. Twelve patients had a platinum-based therapy prior to treatment, 1 patient was on a checkpoint inhibitor, 1 patient was on PD-L1 inhibitor, 2 patients were on an EGFR inhibitor, and 4 patients had no prior treatment.

Safety data did not show any new safety signals and the continued accrual of these data showed that adverse events (AEs) were consistent with CUE-101 mechanisms of action and underlying disease. Overall, 95.5% of patients had an adverse event (AE) of any grade compared with 40.9% who experienced grade 3 or higher AEs. However, 81.8% of patients treated in this study thus far had a treatment related AE of any grade with 24.1% being grade 3 or higher. The most common treatment-related AEs of any grade were fatigue (30.3%), chills (22.7%), infusion related reaction (25.8%), and nausea (18.2%), with the most common grade 3 or higher AE being fatigue (3%).

“Initiation of the phase 1 trial evaluating our second IL-2-based biologic, CUE-102, is also an important milestone for the company as we continue to demonstrate the versatility and modularity of our platform to potentially treat multiple cancers,” concluded Anish Suri, PhD, president, and chief scientific officer of Cue Biopharma, in the press release.

1. Cue biopharma presents new positive data from ongoing phase 1 trial of CUE-101 in combination with KEYTRUDA(R) for recurrent/metastatic HPV+ head and neck cancer at the society for immunotherapy of cancer’s (SITC) 37th annual meeting. Cue Biopharm, Inc. November 10, 2022. Accessed November 14, 2022.
2. Chung C, Colevas A, Adkins d, et al. A phase 1 study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer. Presented at: Society for Immunotherapy of Cancer’s 37th Annual Meeting; November 10th-14th, 2022; Boston, MA. Abstract 607. Accessed November 14, 2022.
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