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

Overseen By Stephanie Ladd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Metastases, Autoimmune disease, Cardiovascular, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment approach for head and neck cancer linked to HPV-16. Researchers are exploring CUE-101 (an experimental treatment) alone and in combination with pembrolizumab (an immunotherapy drug) to evaluate their effects before surgery. The trial seeks individuals with HPV-16 positive head and neck cancer that cannot be surgically removed without major complications. Participants should not have received prior cancer treatments for this specific type of head and neck cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like corticosteroids above a specific dose or if you have received certain vaccines recently. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

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

A previous study found CUE-101 to be safe and well-tolerated for patients with head and neck cancer. Patients received CUE-101 through an IV and managed it well without serious side effects. Another study tested CUE-101 combined with pembrolizumab, and this combination also demonstrated good safety results, with manageable side effects.

Pembrolizumab, used widely on its own, carries some risk of side effects. However, its approval for other cancer treatments indicates a well-understood safety profile.

Overall, both treatments have demonstrated safety for patients, with CUE-101 as a newer treatment showing promising early results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Head and Neck Squamous Cell Carcinoma because they offer new ways to fight the disease. Unlike traditional treatments like surgery, radiation, and chemotherapy, CUE-101 is an immunotherapy designed to specifically target and activate immune cells against cancer cells. Pembrolizumab, another immunotherapy, works by blocking the PD-1 pathway, enhancing the body's immune response to cancer. The combination of CUE-101 and Pembrolizumab could potentially boost the immune system's ability to attack cancer cells more effectively than current options. This novel approach aims to improve outcomes and offer hope for patients who might not respond well to existing treatments.

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 pembrolizumab holds promise for treating HPV-positive head and neck cancer. Studies have found that this combination has a 50% response rate, with patients living for an average of 32 months. In this trial, participants may receive CUE-101 alone, which has demonstrated an average survival of 20.8 months. Alternatively, some participants will receive pembrolizumab alone, which has also proven effective, extending patient survival compared to other treatments. Both treatments are being tested together in one of the trial arms because they might work better in combination than separately. ^{2 5 6 7 8}

Who Is on the Research Team?

Sara Pai, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for HLA-A*0201-positive individuals with HPV-16 associated head and neck squamous cell carcinoma (HNSCC) that hasn't spread too far or been treated yet. Participants must be treatment-naive, meaning they haven't received any previous therapies for their cancer.

Inclusion Criteria

Participants must have measurable disease as defined in the protocol

Ability to understand and sign a written informed consent document

I have a new diagnosis of advanced but non-spreading head and neck cancer.

Exclusion Criteria

History of prior allogeneic transplantation

Pregnant or breastfeeding women

Positive urine pregnancy test within 72 hours prior to first dose of study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive CUE-101 monotherapy, pembrolizumab monotherapy, or a combination of CUE-101 and pembrolizumab as neoadjuvant therapy

3 weeks

2 visits (in-person)

Surgical Resection

Participants undergo definitive surgical resection following neoadjuvant therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CUE-101
• Pembrolizumab

Trial Overview The study is testing CUE-101 alone and in combination with Pembrolizumab to see how safe and effective they are as initial treatments. It's a phase 2 trial where patients are randomly assigned to one of three groups, including a control group, in an open-label setting.

How Is the Trial Designed?

Group I: Neoadjuvant Pembro Experimental Treatment 1 Intervention

Pembrolizumab Neoadjuvant therapy followed by definitive surgical resection

Group II: Neoadjuvant CUE-101 + Pembro Experimental Treatment 2 Interventions

CUE-101+Pembrolizumab as neoadjuvant therapy followed by definitive surgical resection

Group III: Neoadjuvant CUE-101 Experimental Treatment 1 Intervention

Neoadjuvant therapy followed by definitive surgical resection

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Cue Biopharma

Industry Sponsor

Trials

3

Recruited

160+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 ... A median OS of 20.8 was observed in patients treated with CUE-101 monotherapy as post-platinum/CPI therapy. CUE-101 continues to demonstrate ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT07172256

CUE-101with Pembrolizumab for LA-HPV+HNSCCs This secondary outcome measure aims to evaluate the radiologic response rate among participants at the conclusion of neoadjuvant treatment.

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. 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11986418/

Outcomes for recurrent or metastatic head and neck cancer ... This analysis aims to assess differential outcomes specific to HPV+ and HPV− R/M HNSCC to reflect HPV-associated prognostic considerations.