Intratumoral Microdosing for Head and Neck Cancer

Recruiting at 8 trial locations

Overseen By Presage Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Presage Biosciences

Must not be taking: Immune therapy, ADCs

Disqualifiers: Concurrent cancer, Immune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1-3 days

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat head and neck cancer by injecting small doses of experimental drugs directly into tumors. The goal is to compare how these drugs interact with cancer cells against the standard treatment, pembrolizumab (also known as KEYTRUDA), which is also administered in small amounts. Suitable participants include those with head and neck squamous cell carcinoma with a surface-accessible tumor who are already scheduled for surgery. As an Early Phase 1 trial, this 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research shows that rilvegostomig is generally safe, with most side effects mild and manageable. Studies indicate that volrustomig is also well-tolerated and safe for patients. However, the safety of sabestomig remains unclear as it is still under study.

Pembrolizumab, an FDA-approved treatment for certain head and neck cancers, demonstrated a well-understood safety profile in studies with 192 patients, indicating it is generally safe with manageable side effects.

The investigational drugs are in early testing stages, so researchers are still gathering safety information. However, current data suggests these treatments are well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a novel approach to treating head and neck cancer by using intratumoral microdosing. Unlike standard treatments that often involve systemic therapies, this method delivers microdoses of drugs directly into the tumor, potentially enhancing effectiveness while minimizing side effects. It employs the CIVO device to administer combinations of promising agents like rilvegostomig, volrustomig, sabestomig, AZD9592, and pembrolizumab right where they're needed most. This direct delivery could offer a more personalized treatment strategy, allowing doctors to see which drugs work best for each patient before surgery.

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

In this trial, participants will receive microdoses of different investigational treatments to evaluate their effects on head and neck cancer. Research has shown that rilvegostomig, which targets the proteins PD-1 and TIGIT, can help the immune system kill cancer cells more effectively than treatments targeting just one of these proteins. Another treatment option in this trial, volrustomig, targets PD-1 and CTLA-4 and has shown promise in treating various cancers, including head and neck cancer. Sabestomig, which targets PD-1 and TIM-3, has demonstrated some ability to fight tumors in early studies, though results have been mixed. Lastly, pembrolizumab, which participants in this trial may also receive, has been proven to improve survival rates in patients with head and neck squamous cell carcinoma, according to several studies. All these treatments work by helping the immune system attack cancer cells, and early results are promising. ^{4 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Presage Biosciences

Are You a Good Fit for This Trial?

This trial is for individuals with accessible lesions from Head and Neck Squamous Cell Carcinoma (HNSCC), including Oral Squamous Cell Carcinoma, who are already scheduled for tumor removal surgery. Participants must have a lesion that can be reached for intratumoral drug delivery.

Inclusion Criteria

Ability and willingness to comply with the study's visits and assessment schedule

I am able to care for myself and perform daily activities.

I am a woman who is either postmenopausal, cannot have children, or will use effective birth control.

Exclusion Criteria

My tumor or lymph nodes do not have enough viable tissue for a specific injection.

My tumor is too close to vital body parts, making treatment injections risky.

I have had immune therapy in the past 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intratumoral microdose injections of investigational drugs using the CIVO device

1-3 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Rilvegostomig
• Sabestomig
• Volrustomig

Trial Overview The study tests the effects of three drugs—Rilvegostomig, Volrustomig, Sabestomig—delivered directly into the tumor using a device called CIVO. These effects are compared to those of Pembrolizumab, another drug given in the same way.

How Is the Trial Designed?

Group I: Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab Experimental Treatment 9 Interventions

HNSCC patients presenting with a surface accessible lesion who are scheduled for tumor and/or regional node dissection as part of their standard treatment will be injected one to three days prior to surgery using the CIVO device. The planned injection scheme includes: vehicle control and microdoses of rilvegostomig, volrustomig, sabestomig, AZD9592, and pembrolizumab as single agents and AZD9592 drug combinations with the evaluated biologics.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Presage Biosciences

Lead Sponsor

Trials

10

Recruited

110+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

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]

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, 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]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219809/

Updated Results of the Phase III KEYNOTE-048 Study - PubMed Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

3. merck.com merck.com/news/european-commission-approves-keytruda-pembrolizumab-as-part-of-a-treatment-regimen-for-adults-with-resectable-locally-advanced-head-and-neck-squamous-cell-carcinoma-la-hnscc-expressing-pd-l1/

European Commission Approves KEYTRUDA ... “This approval brings a promising advancement to patients in Europe with resectable locally advanced head and neck squamous cell carcinoma,” ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6012

Neoadjuvant and adjuvant pembrolizumab plus standard ... The randomized phase 3 KEYNOTE-689 study (NCT03765918) showed significantly improved event-free survival (EFS) with neoadjuvant/adjuvant pembrolizumab + SOC vs ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda

pembrolizumab (KEYTRUDA) Safety data was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks ...

7. keytrudahcp.com keytrudahcp.com/safety/adverse-reactions/hnscc-squamous-cell-carcinoma/

KEYNOTE-689: Selected Safety Data and Adverse Reactions The safety of KEYTRUDA was investigated in 676 patients with resectable locally advanced (stage III–IVA) head and neck squamous cell carcinoma. A total of 361 ...

8. keytruda.com keytruda.com/head-and-neck-cancer/

head and neck squamous cell cancer (HNSCC) FDA-APPROVED FOR PEOPLE WITH CERTAIN TYPES OF HEAD AND NECK SQUAMOUS CELL CANCER · Understanding KEYTRUDA · Treatment information and clinical trial results · What ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02358031

NCT02358031 | A Study of Pembrolizumab (MK-3475) for ... A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma