CUE-101 + Keytruda for Head and Neck Squamous Cell Carcinoma

Not currently recruiting at 18 trial locations

Overseen By Steven Margossian, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cue Biopharma

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment using CUE-101, alone or with Keytruda (Pembrolizumab, an immunotherapy drug), for individuals with a specific type of head and neck cancer. The focus is on those whose cancer is linked to HPV16 and has recurred or spread after previous treatments. The researchers aim to assess how well these treatments work together to fight tumors and boost the immune system. Individuals whose head and neck cancer has returned or spread, and who have previously received chemotherapy or Keytruda, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain treatments like systemic anti-cancer therapy or radiation therapy within a few weeks before starting the study drug. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CUE-101 is safe and well-tolerated when used alone. One study found that patients who received CUE-101 before other treatments tolerated it well. When combined with Keytruda (pembrolizumab), CUE-101 also demonstrates good safety and tolerability. Although detailed safety information for the combination of CUE-101 and Keytruda remains limited, pembrolizumab alone has been safely used in many other studies. This combination has shown promising results, with patients experiencing significant improvements in head and neck cancer studies. While this trial is in its early stages and more safety data is still being collected, the current findings are encouraging for those considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CUE-101 combined with Keytruda for head and neck squamous cell carcinoma because it offers a novel approach to tackling this cancer. Unlike standard treatments like surgery, radiation, or chemotherapy, CUE-101 is a biologic drug designed to engage the immune system more precisely by targeting a specific protein found on cancer cells. When used alongside Keytruda, an established immunotherapy, CUE-101 may enhance the immune system's ability to recognize and fight cancer cells more effectively. This combination aims to provide a more targeted and potentially more effective treatment option with fewer side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for Head and Neck Squamous Cell Carcinoma?

Research has shown that using CUE-101 with Keytruda (pembrolizumab) yields promising results for treating HPV-positive head and neck cancer. This trial will include a treatment arm where participants receive this combination, which has reduced tumors in 50% of patients in previous studies. In some studies, 88% of patients survived after 12 months, indicating a high survival rate. Another arm of this trial will study CUE-101 alone, which has also proven beneficial, with patients living for about 21 months on average. These findings suggest that CUE-101, especially when combined with Keytruda, could effectively treat this type of cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Matteo Levisetti, MD

Principal Investigator

Cue Biopharma

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HPV16+ recurrent or metastatic head and neck squamous cell carcinoma who've had prior systemic therapy. They must have measurable disease, be HLA A*0201 genotype positive, and able to consent to study procedures. Exclusions include HIV/AIDS, hepatitis B/C, other cancers within 2 years, recent major surgery or trauma, significant heart disease, active infections requiring IV treatment, mental incapacity to consent.

Inclusion Criteria

Results from medical tests show certain abnormalities or conditions.

You have advanced head and neck cancer that has worsened after receiving at least one type of treatment. You must have already received platinum-based chemotherapy and/or pembrolizumab as a first-line treatment.

You fully understand the study and have agreed to participate. You are also willing to follow the study procedures and provide the necessary research samples.

Exclusion Criteria

Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome

Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction

Second primary invasive malignancy that has not been in remission for >2 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

CUE-101 Monotherapy IV infusion Q3W Dose Escalation and Expansion, and CUE-101 Dose Escalation in Combination with Pembrolizumab

36 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• CUE-101
• Keytruda

Trial Overview The trial is testing CUE-101 alone as a second-line treatment or in combination with Pembrolizumab (KEYTRUDA®) as a first-line treatment. It's an open-label phase 1 study focusing on safety and effectiveness against HPV16+ head and neck cancer.

How Is the Trial Designed?

Group I: Pembrolizumab and CUE-101 Experimental Treatment 2 Interventions

Part C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)

Group II: CUE-101 dose escalation and expansion Experimental Treatment 1 Intervention

Part A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B)

Who Is Running the Clinical Trial?

Cue Biopharma

Lead Sponsor

Trials

3

Recruited

160+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6004

A phase 1 dose-escalation and expansion study of CUE ... CUE-101 continues to demonstrate safety, tolerability and meaningful clinical benefit in patients with HPV16+ R/M HNSCC.

2. oncodaily.com oncodaily.com/oncolibrary/cue-101-331017

CUE-101 and Pembrolizumab Show Promising Results in ... CUE-101 with pembrolizumab shows 50% response and 32-month OS in HPV-positive HNSCC. A novel T-cell therapy with strong early-phase clinical ...

3. targetedonc.com targetedonc.com/view/cue-101-pembrolizumab-shows-promising-response-survival-in-first-line-hpv-hnscc

CUE-101/Pembrolizumab Shows Promising Response ... CUE-101 combined with pembrolizumab shows promising results, achieving a 50% response rate in HPV-positive head and neck cancer patients.

4. cuebiopharma.gcs-web.com cuebiopharma.gcs-web.com/news-releases/news-release-details/cue-biopharma-reports-new-complete-response-and-confirmed-50

Cue Biopharma Reports New Complete Response and ... Cue Biopharma reports new complete response and confirmed 50% overall response rate in ongoing Phase 1 trial of CUE-101 and pembrolizumab in recurrent/ ...

5. onclive.com onclive.com/view/cue-101-plus-pembrolizumab-yields-50-orr-in-hpv-hnscc-with-low-pd-l1-expression

CUE-101 Plus Pembrolizumab Yields 50% ORR in HPV+ ... In patients with HPV16-positive HNSCC, CUE-101 plus pembrolizumab generated 2 complete responses and a 12-month overall survival rate of 88%.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18086

Safety of administration of CUE-101, a novel HPV16 E7- ... Administration of CUE-101 (4 mg/kg IV) 14 days (Schedule A) and 14 and 7 days (Schedule B) before curative-intent treatment was safe and tolerable.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07172256

CUE-101with Pembrolizumab for LA-HPV+HNSCCs This is a phase 2, pilot, randomized, open-label 3-arm study to assess the safety, tolerability, and efficacy of CUE-101 monotherapy, ...

8. cuebiopharma.gcs-web.com cuebiopharma.gcs-web.com/news-releases/news-release-details/cue-biopharma-presents-updated-data-phase-1-trial-cue-101

Cue Biopharma Presents Updated Data from Phase 1 Trial of ... Overall response rate (ORR) of 46% and 12-month overall survival (OS) of 96% in first line (1L) recurrent/metastatic (R/M) HPV+ head and neck squamous cell ...

9. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A764

674 A phase 1 dose-escalation and expansion study ... CUE-101–01 is an ongoing first-in-human study in HLA-A*0201 patients with HPV16+ recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).