KEY TAKEAWAYS
- The phase I trial aimed to enhance HPV16-specific CD8+ T cell activity in HNSCC patients by activating tumor-antigen-specific T cells.
- The study concluded that CUE-101 is safe, well-tolerated, and effective in treating HPV16+ R/M HNSCC patients.
Immuno-STATs are engineered to activate tumor-antigen-specific CD8+ T cells via cytokine delivery. CUE-101, comprising HLA-A*0201, HPV16 E7 peptide, and attenuated IL-2, targets HPV16-specific CD8+ T cells for head and neck cancer immunotherapy.
A. Dimitrios Colevas and his team spearheaded the study that aimed to develop immuno-STATs for targeted activation of HPV16-specific CD8+ T cells using CUE-101, facilitating effective immunotherapy against HPV-associated cancers.
CUE-101-01 is a continuing phase I clinical trial conducted in patients with HLA-A*0201 who have HPV16-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
The study assessed escalating doses of CUE-101 in patients refractory to platinum-based chemotherapy or immune checkpoint blockade (ICB) in the recurrent or metastatic setting or combination with pembrolizumab (pembro) as first-line treatment for recurrent or metastatic HNSCC. Following the determination of the recommended phase 2 dose (RP2D), enrollment was expanded. The trial evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and therapeutic efficacy of CUE-101.
About 76 patients have been enrolled in the study. Following dose escalation with both monotherapy and combination therapy, a dosage of 4 mg/kg of CUE-101 was selected as the recommended phase 2 dose (RP2D) for both groups. Enrollment in both the monotherapy and combination therapy arms is now closed. Grade 3 treatment-related adverse events (TRAEs) included infusion-related reactions (4.2%), fatigue, maculopapular rash, stomatitis, and diarrhea (all 2.7%).
Among the 19 evaluable patients treated with monotherapy at the RP2D, one achieved a partial response (PR), and six had durable stable disease (SD) lasting at least 12 weeks, with a median overall survival (mOS) of 20.8 months. In the RP2D combination therapy group, among the 17 evaluable patients, one had a complete response (CR), seven had PRs, and three had durable SDs. Cr and 5 out of 7 PRs occurred in tumors with a combined positive score (CPS) of 20 or less. Of the 8 patients with objective responses, 5 achieved a reduction of more than 99% in HPV16 circulating free DNA (cfDNA), 4 by week 6, with 3 patients pending analysis at the time of data cut-off.
The study concluded that CUE-101 exhibits favorable safety and tolerability profiles alongside significant anticancer efficacy. Notably, patients administered CUE-101 monotherapy as third-line treatment demonstrated prolonged overall survival. Furthermore, the combination of CUE-101 and pembro yielded a noteworthy % ORR of 47% and reduced levels of HPV16 circulating free DNA in first-line treatment for patients with HPV16-positive recurrent or metastatic HNSCC. Funding was provided by Cue Biopharma.
monotherapy as third-line treatment demonstrated prolonged overall survival. Furthermore, the combination of CUE-101 and pembro yielded a noteworthy % ORR of 47% and reduced levels of HPV16 circulating free DNA in first-line treatment for patients with HPV16-positive recurrent or metastatic HNSCC. Funding was provided by Cue Biopharma.
Source: https://astro.confex.com/astro/hncs2024/meetingapp.cgi/Paper/59599
Clinical Trial: https://clinicaltrials.gov/study/NCT03978689
Colevas AD, Chung CH, Adkins D, et al. (2024). “A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy in 3rd line and in combination with pembrolizumab in 1st line recurrent/metastatic (R/M) HPV16+ head and neck cancer patients.” Presented at MHNCS 2024 (Abstract 257).
