Viral Therapy + Pembrolizumab for Head and Neck Cancer

No longer recruiting at 37 trial locations

Overseen By Backup Hookipa Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hookipa Biotech GmbH

Must be taking: Pembrolizumab

Must not be taking: Immunosuppressive therapy

Disqualifiers: CNS disease, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with certain types of HPV 16+ cancers, specifically in the head and neck area. Researchers are testing two experimental viral therapies, HB-201 and HB-202, alone or in combination with the drug pembrolizumab, to evaluate their effectiveness in controlling cancer. The trial seeks participants whose cancer has progressed or returned after standard treatments and who have confirmed HPV 16+ cancers. Individuals with head and neck cancer that has progressed after initial treatment might be suitable for this study. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you must meet certain 'washout periods' (time without taking certain medications) for prohibited medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that HB-201 and HB-202 treatments are generally well-tolerated. Early safety reports indicate that patients did not experience severe side effects. Some patients had mild to moderate reactions, but these were manageable. This suggests these treatments are likely safe.

For pembrolizumab, the evidence is stronger. It is already approved for treating several cancers, including head and neck cancers. Studies have shown that pembrolizumab is generally safe. Some patients may experience side effects like tiredness or a rash, but these are usually mild.

In summary, current studies suggest that HB-201, HB-202, and pembrolizumab are safe. However, as with any treatment, individual reactions can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments HB-201 and HB-202 because they represent a novel approach to tackling head and neck cancers, particularly those linked to HPV 16. Unlike standard therapies like surgery, radiation, or chemotherapy, these treatments use viral therapy, which involves using engineered viruses to specifically target and kill cancer cells. This innovative mechanism has the potential to boost the immune response against cancer cells more effectively. Additionally, combining these viral therapies with pembrolizumab, an immune checkpoint inhibitor, might enhance the overall effectiveness by unleashing the immune system's full power to combat the cancer. This combination approach is promising and could offer new hope for patients whose cancer has progressed despite standard treatment options.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Studies have shown that HB-201 and HB-202, treatments tested in this trial, can help treat HPV 16+ head and neck cancers. Early research found that HB-201 helped 18% of patients who had already tried several other treatments. When used together, HB-201 and HB-202 have shown potential in preventing cancer recurrence. Pembrolizumab, another treatment option in this trial, has proven to help head and neck cancer patients live longer. In real-world cases, it has also benefited patients with cancer that has returned or spread. These treatments, studied in different arms of this trial, offer new hope for those facing this challenging disease. ^{5 6 7 8 9}

Who Is on the Research Team?

Head of Clinical Development

Principal Investigator

Hookipa Biotech GmbH

Are You a Good Fit for This Trial?

This trial is for patients with HPV16+ recurrent or metastatic head and neck squamous cell carcinoma and other cancers. Participants must have an ECOG performance status of 0 to 1, at least one measurable lesion, meet specific lab value criteria, and be eligible for pembrolizumab treatment. They cannot join if they have autoimmune disorders requiring immunosuppression, a life expectancy under three months, certain infections like hepatitis B/C or AIDS, severe allergies to the drugs used in the study or prior severe reactions to similar treatments.

Inclusion Criteria

I have at least one tumor that can be measured on scans.

Screening laboratory values must meet protocol-specified criteria.

I am assigned to either Treatment Group E or F.

Exclusion Criteria

Has a life expectancy of less than 3 months.

I stopped my previous cancer treatment due to a severe immune system side effect.

I have been diagnosed with AIDS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Dose Escalation

Determine the recommended Phase II dose based on incidence of dose-limiting toxicities

3-4 weeks

Multiple visits for dose administration and monitoring

Phase II Dose Expansion

Assess the preliminary antitumor activity and safety of dosage regimens of HB-201 and HB-202

Up to 30 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HB-201
• HB-202
• Pembrolizumab

Trial Overview The trial tests HB-201 alone or alternating with HB-202 intravenous therapies in combination with pembrolizumab against standard care regimens including pembrolizumab. It's a Phase I/II study that includes dose escalation (finding the right drug amount) and expansion (testing it on more people). Some participants may also use a CD8 PET Tracer for imaging studies.

How Is the Trial Designed?

Group I: Ph II, Group F Experimental Treatment 1 Intervention

Patients with HPV 16+ cancers who had tumor progression or recurrence on standard of care therapy and who are eligible to receive pembrolizumab as part of 2L+ standard of care..

Group II: Ph II, Group E Experimental Treatment 1 Intervention

Patients with HPV 16+ HNSCC who are eligible to receive pembrolizumab as part of 1L standard of care.

Group III: Ph II, Group B Experimental Treatment 1 Intervention

Patients with HPV 16+ HNSCC who are eligible to receive immune checkpoint inhibitor as part of standard of care.

Group IV: Ph I, sub-study Experimental Treatment 1 Intervention

Patients with HPV 16+ HNSCC who had tumor progression or recurrence on standard of care therapy

Group V: Ph I, Group 3 and Group 4 Experimental Treatment 1 Intervention

Patients with HPV 16+ HNSCC or Non-HNSCC who had tumor progression or recurrence on standard of care therapy.

Group VI: Ph I, Group 1 and Group 2 Experimental Treatment 1 Intervention

Patients with HPV 16+ HNSCC or Non-HNSCC who had tumor progression or recurrence on standard of care therapy.

Who Is Running the Clinical Trial?

Hookipa Biotech GmbH

Lead Sponsor

Trials

9

Recruited

1,100+

Published Research Related to This Trial

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]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

In a study of 34 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with PD-1 inhibitors, 29% experienced hyperprogression, where tumor growth accelerated during treatment.

Hyperprogression was significantly associated with regional recurrence, leading to shorter progression-free survival, but did not affect overall survival, highlighting the need for further research into the mechanisms behind this phenomenon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Saâda-Bouzid, E., Defaucheux, C., Karabajakian, A., et al.[2022]

In a study of 646 adults with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), real-world outcomes showed that pembrolizumab, whether used alone or with chemotherapy, provided similar overall survival rates to those seen in clinical trials, with median overall survival of 12.1 months for monotherapy and 11.9 months for combination therapy.

Factors such as HPV-positive tumor status and lower Eastern Cooperative Oncology Group performance status were associated with longer overall survival, highlighting the importance of tumor characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma. Black, CM., Hanna, GJ., Wang, L., et al.[2023]

In a study of 36 patients with resectable HPV-unrelated head and neck squamous-cell carcinoma, neoadjuvant pembrolizumab was found to be safe, with no serious adverse events reported during treatment.

The treatment resulted in a pathologic tumor response in 44% of patients, and the one-year relapse rate for those with high-risk pathology was significantly lower at 16.7%, compared to the historical rate of 35%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Uppaluri, R., Campbell, KM., Egloff, AM., et al.[2021]

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 of 139 patients with recurrent and metastatic head and neck squamous cell carcinoma, pembrolizumab monotherapy showed similar long-term survival rates compared to combination therapy with chemotherapy, with 2-year progression-free survival at 28.6% and overall survival at 41.8%.

Patients receiving pembrolizumab monotherapy who experienced adverse events had a better prognosis than those without adverse events, suggesting that monotherapy may be a safer and more effective long-term treatment option compared to combination therapy, which did not improve prognosis and could lead to more side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Monotherapy Versus Pembrolizumab Plus Chemotherapy in Patients With Head and Neck Squamous Cell Carcinoma. Matsuo, M., Masuda, M., Yamauchi, M., et al.[2023]

A 69-year-old patient with relapsed squamous cell carcinoma showed significant improvement after 14 cycles of pembrolizumab, indicating its efficacy as a second-line treatment for metastatic head and neck cancer.

The patient developed severe immune-related adverse effects, specifically grade 4 mucositis and esophagitis, highlighting the importance of monitoring for such complications in patients receiving PD-1 inhibitors like pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. Acero Brand, FZ., Suter, N., Adam, JP., et al.[2019]

Pembrolizumab has been approved by the FDA as the first-line treatment for both HPV-positive and HPV-negative recurrent head and neck squamous cell carcinoma, marking it as a significant advancement in immunotherapy for this cancer type.

The approval allows pembrolizumab to be used either alone for tumors expressing PD-L1 or in combination with chemotherapy, highlighting the need for healthcare providers to be aware of and manage potential immune-related toxicities such as dermatitis and mucositis associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. Fazer, C., Price, KA.[2021]

In a study of adult patients with metastatic head and neck squamous cell cancer, substituting 5-fluorouracil (5-FU) with a taxane in a pembrolizumab-based treatment regimen did not increase toxicity or worsen survival outcomes.

Patients receiving the taxane combination experienced significantly lower rates of mucositis and elevated creatinine levels compared to those on the 5-FU regimen, indicating a better safety profile for the taxane approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. Lee, B., Chehab, SS., Fan, W., et al.[2023]

Immune checkpoint inhibitors, like nivolumab and pembrolizumab, have become the standard treatment for recurrent or metastatic head and neck squamous cell carcinoma that cannot be treated with surgery or radiotherapy.

Nivolumab is approved for use regardless of PD-L1 expression in patients who have progressed after platinum therapy, while pembrolizumab requires specific conditions related to PD-L1 expression and prior treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

["Immunotherapy in head and neck squamous cell carcinoma"]. Marret, G., Borcoman, É., Le Tourneau, C.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05108870

Study Details | NCT05108870 | TheraT® Vectors (Vaccines ... Doctors leading this study hope to learn about the safety and effectiveness of combining medications HB-201 and HB-202 (also known as TheraT® vectors) with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS6115

Randomized phase I/II trial of TheraT vectors expressing ... Data from in vivo models and early phase clinical studies indicate that HB-201 monotherapy and HB-201/HB-202 alternating two-vector therapy ...

3. ir.hookipapharma.com ir.hookipapharma.com/news-releases/news-release-details/hookipa-interim-phase-1-monotherapy-data-hb-201-treatment

HOOKIPA Interim Phase 1 Monotherapy Data of HB-201 for ... As per RECIST1.1, in patients with third-line or later HNSCC, HB-201 demonstrated an unconfirmed response rate of 18% (one unconfirmed complete ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12115775/

Update: Immunotherapeutic Strategies in HPV-Associated ... Interim results from an ongoing phase I study in HPV-16-positive recurrent/metastatic HNSCC demonstrated an ORR of 47% and median PFS of 5.8 ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/23-293

A Phase 2 Study of HB-202/HB-201 in People With HPV 16 ... Researchers want to see how well the drugs HB-202 and HB-201 work to keep head and neck cancer from coming back. The people in this study have squamous cell ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06373380

NCT06373380 | A Study of HB-202/HB-201 in People With ... The researchers are doing this study to find out if HB-202/HB-201 is a feasible treatment for people with HPV 16-positive head and neck squamous cell cancer ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09805

A Study of HB-202/HB-201 With Pembrolizumab in Patients ... This trial studies whether administering HB-202/HB-201 alternating 2-vector therapy with pembrolizumab works better in more participants by shrinking their ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.2502

First report of the safety/tolerability and preliminary ... HB-201 monotherapy and HB-201 & HB-202 2-vector alternating therapy were generally well-tolerated and showed preliminary antitumor activity as monotherapy.

9. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04180215/

Clinical Trial: NCT04180215 - HNSCC HB-201 intravenous administration. Ph I, Group 2, Experimental, Patients with HPV 16+ cancers with a safe and accessible tumor site amenable ...