Viral Therapy + Pembrolizumab for Head and Neck Cancer

Recruiting at 34 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

200 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug pembrolizumab for head and neck cancer?

Pembrolizumab has been shown to be effective for treating recurrent or metastatic head and neck squamous cell carcinoma, with studies indicating it can improve survival and response rates, especially when used as a first-line treatment or in combination with chemotherapy. ^{1 2 3 4 5}

What safety information is available for pembrolizumab in head and neck cancer treatment?

Pembrolizumab, used for head and neck cancer, can cause side effects like diarrhea, skin rash, and thyroid issues, with rare severe lung inflammation. It's important to monitor and manage these side effects early. ^{3 6 7 8 9}

What makes the Viral Therapy + Pembrolizumab treatment unique for head and neck cancer?

The Viral Therapy + Pembrolizumab treatment is unique because it combines a viral therapy (HB-201, HB-202) with pembrolizumab, an immune checkpoint inhibitor, potentially enhancing the immune system's ability to target cancer cells in head and neck cancer, which is different from standard treatments that typically involve pembrolizumab alone or with chemotherapy. ^{1 3 10 11 12}

What is the purpose of this trial?

This trial is testing two new drugs, HB-201 and HB-202, which aim to help the immune system fight HPV 16-related cancers. It focuses on patients with advanced head and neck cancer who are also receiving a standard treatment called pembrolizumab. The goal is to see if these new drugs can improve the body's ability to combat cancer.

Research Team

Head of Clinical Development

Principal Investigator

Hookipa Biotech GmbH

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

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 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]

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]

References

1. United States 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. [2023]

2. France pubmed.ncbi.nlm.nih.gov

["Immunotherapy in head and neck squamous cell carcinoma"]. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. [2019]

4. Switzerland 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. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

New developments in the management of head and neck cancer - impact of pembrolizumab. [2022]

6. United States 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

8. United States 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. [2021]

9. England 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. [2023]

10. United States 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. [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

Pembrolizumab Monotherapy Versus Pembrolizumab Plus Chemotherapy in Patients With Head and Neck Squamous Cell Carcinoma. [2023]

12. England 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. [2022]