T-Cell Engagers Show Potential in HPV16+ and WT1+ Cancers

Christine H. Chung, MD

Cue Biopharma’s T-cell engager (TCE) therapies CUE-101 and CUE-102 have shown promising efficacy in safety in recurrent/metastatic HPV16+ head and neck squamous cell carcinoma (HNSCC) and Wilms’ Tumor 1 (WT1)-positive recurrent/metastatic cancers, respectively.^1,2

The company reported data from the clinical trials evaluating CUE-101 (CUE-101-01; NCT03978689) and CUE-102 (CUE-102-01; NCT05360680) at The Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting, held November 1-5 in San Diego, California. Data from CUE-101-01 were reported by Christine H. Chung, MD, department chair, head and neck-endocrine oncology, Moffitt Cancer Center, and data from CUE-102-01 were reported by Jennifer Eva Selfridge, MD, PhD, assistant professor of medicine, Case Comprehensive Cancer Center, Case Western Reserve University.

“I am pleased to observe the clinical benefit patients are deriving and encouraged by the positive enhancement of data from the CUE-101 clinical trials,” Chung, a principal investigator in the CUE-101 trial, said in a statement.³

CUE-101-01 trial enrolled patients with an HLA-A*0201 genotype and HPV16+ HNSCC after platinum or checkpoint inhibitor-based therapies. Patients with 1 prior line of therapy were enrolled (n = 49) in the monotherapy arm, given every 3 weeks, and patients with at least 2 prior lines of therapy (n = 27) were enrolled into the CUE-101 plus 200 mg pembrolizumab arm every 3 weeks.

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Chung and colleagues found that the monotherapy arm had a median overall survival (OS) of 20.8 months (95% CI, 11.0 - not applicable [NA]).The 12-month OS rate is 58.93% (95% CI, 40.60 - 85.54) with 11 patients reaching the 12-month landmark.¹

The pembrolizumab arm had an objective response rate (ORR) of 47%, with 1 complete response (CR) and 7 partial responses (PRs). The CR and 5 PRs occurred in tumors with PD-L1 Combined Positive Score of 20 or less. Disease control rate was 65%. Twenty patients remain alive as of the September 7 data cutoff date, including 8 patients for at least 12 months, and 13 remain on treatment. The Kaplan-Meier estimate of median progression-free survival is 5.8 months (95% CI; 2.6, NA).¹

“The notable prolongation in overall survival to over 20 months in monotherapy represents a significant advancement of clinical benefit compared to the current standard of care for this population with advanced and refractory disease. Similarly, the reported enhanced ORR to date in combination with pembrolizumab, compared to the historical response rate for pembrolizumab alone, is very promising for first line patients,” Chung added.³ “I look forward to evaluating the trial results as they continue to mature and remain highly encouraged by the observations to date. There is a significant unmet medical need for more efficacious and less toxic treatment options for patients with recurrent/metastatic head and neck cancer, and these results from the CUE-101 trial demonstrate the potential to address this need.”

Chung and colleagues found that the adverse events observed were consistent with the CUE-101 mechanism of action, known profile of pembrolizumab and underlying disease. Most treatment-related AEs were grade 2 or less, reversible, and easily managed with appropriate medical care, with a low rate of treatment-related AEs over grade 2.¹

CUE-102-01 has enrolled 18 patients with WT1-expressing cancers including colorectal cancer (50%), pancreatic cancer (33%), ovarian cancer (11%), and gastric/gastro oesophageal junction (GEJ) cancer (6%). WT1 expression was analyzed and 100% of ovarian cancer samples were WT1+, 56% of GEJ cancer samples were WT1+, 53% of pancreatic cancer samples were WT1+, and 60% of colorectal cancer samples were WT1+.²

“It is highly gratifying to share the positive results from the ongoing Phase 1 trial of CUE-101, highlighting its clinical activity in combination with pembrolizumab in 1L patients and the prolonged survival observed in 2L+ patients treated with CUE-101 monotherapy. The promising data further supports our confidence in defining registrational trials for CUE-101, capitalizing on the previously granted Fast Track Designation,” Matteo Levisetti, MD, chief medical officer, Cue Biopharma, added to the statement.3 “Concurrently, the unveiling of positive findings from the ongoing CUE-102 trial have provided early evidence of tolerability and clinical activity, including reductions in tumor burden. These observations are highly encouraging, suggesting that we may have opened up a path for immunotherapy in treating multiple cancers historically resistant to check point inhibitors. The cancers overexpressing WT1 represent substantial patient populations that may benefit from CUE-102 treatment. To date, the CUE-102 trial has been enrolling patients at a rapid pace, reflecting the significant and pressing unmet medical need in these indications.”

CUE-102-01 is escalating doses of 1, 2, 4, and 8 mg/kg CUE-102 every 3 weeks before entering the dose expansion phase. So far, the cohorts have treated 3, 5, 4, and 2 patients, respectively, with DCR rates in evaluable patients of 33%, 80%, 75%, and 50%. Nine of 18 patients remain on treatment. Selfridge and colleagues highlighted 2 patients, 1 with gastric cancer and 1 with ovarian cancer, which have experienced reductions in tumor burden. No dose-limiting toxicities have beenreported to date and amaximum tolerated dosehas not been reached. Cohorts 2, 3 and 4 are being expanded to obtain additional safety and pharmacodynamic information to support the selection of the recommended phase 2, dose expansion part of the trial.² 

“The clinical data generated to date, from both our CUE-101 monotherapy and combination trials in HPV+ R/M HNSCC, as well as the early data observed in our ongoing WT1-specific CUE-102 dose escalation trial, demonstrate what we believe to be a best-in-class approach to immune modulation, and a clear path forward to realizing the full potential of activating the patient’s own immune system against cancer," Dan Passeri, chief executive officer, Cue Biopharma, added.³

Read more coverage of SITC 2023 here.

REFERENCES

1. Chung CH, Colevas AD, Adkins DR, et al. A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy and in combination with pembrolizumab in recurrent/metastatic HPV16+ head and neck cancer patients. Presented at: STIC 38th Annual Meeting; November 1-5, 2023; San Diego, California. Poster #674
2. Selfridge JE, Uboha NV, Saenger Y, et al. A phase 1 trial of CUE-102, a novel WT1-pHLA-IL2-Fc fusion protein in HLAA*0201 positive patients with WT1-positive recurrent/metastatic cancers. Presented at: STIC 38th Annual Meeting; November 1-5, 2023; San Diego, California. Poster #750
3. Cue Biopharma presents new positive data from phase 1 trials of CUE-101 in head and neck cancer and CUE-102 in Wilms’ Tumor 1 positive cancers at SITC 2023. News release. Cue Biopharma. November 3, 2023. https://cuebiopharma.gcs-web.com/news-releases/news-release-details/cue-biopharma-presents-new-positive-data-phase-1-trials-cue-101