Ficerafusp Alfa + Pembrolizumab for Head and Neck Cancer

(FORTIFI-HN01 Trial)

Recruiting at 16 trial locations

Overseen By Carrie Smith, Senior Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Bicara Therapeutics

Must not be taking: Anti-TGFβ, Anti-EGFR, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 1 year for Phase 2 and 3 years for Phase 3

650 Participants Needed

Trial Summary

What is the purpose of this trial?

Ficerafusp alfa is directed against two targets, Epidermal Growth Factor Receptor (EGFR) and Transforming Growth Factor beta (TGF-β). This study intends to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab versus placebo with pembrolizumab in 1L PD-L1-positive, recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications like corticosteroids or immunosuppressive drugs, you may need to stop them 7 days before starting the trial treatment.

What data supports the effectiveness of the drug Ficerafusp Alfa + Pembrolizumab for head and neck cancer?

Research shows that pembrolizumab, one of the drugs in the combination, is effective in treating head and neck cancer, especially in patients with high levels of PD-L1, a protein that helps cancer cells hide from the immune system. ^{1 2 3 4 5}

Is the combination of Ficerafusp Alfa and Pembrolizumab safe for humans?

Pembrolizumab, used in treating head and neck cancer, generally has a manageable safety profile, with common side effects like diarrhea, thyroid issues, and skin rash, and rare severe lung inflammation. However, specific safety data for Ficerafusp Alfa in combination with Pembrolizumab is not provided in the available research. ^{1 3 6 7 8}

What makes the drug Ficerafusp Alfa + Pembrolizumab unique for head and neck cancer?

Ficerafusp Alfa combined with Pembrolizumab is unique because it potentially offers a novel approach by combining two different mechanisms: Ficerafusp Alfa's specific action (details not provided) with Pembrolizumab's ability to block PD-1, a protein that helps cancer cells evade the immune system. This combination could enhance the immune system's ability to fight head and neck cancer compared to using Pembrolizumab alone. ^{1 2 3 9 10}

Eligibility Criteria

This trial is for adults with PD-L1-positive, recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) who haven't been treated before. Participants must meet certain health standards but specific inclusion and exclusion criteria are not provided here.

Inclusion Criteria

I am 18 years old or older.

My organs are functioning well.

I haven't had systemic therapy for advanced disease and finished any other therapy over 6 months ago.

Exclusion Criteria

I haven't had any major bleeding episodes recently.

I have not received a live vaccine in the last 4 weeks.

My condition can be treated with the goal of curing it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ficerafusp alfa or placebo in combination with pembrolizumab. Phase 2 involves dose finding, and Phase 3 focuses on efficacy comparison.

Approximately 1 year for Phase 2 and 3 years for Phase 3

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and response duration.

Up to 3 years

Treatment Details

Interventions

• Ficerafusp Alfa

Trial Overview The study tests the effectiveness of a new drug called Ficerafusp alfa, which targets EGFR and TGF-β, in combination with an existing cancer drug Pembrolizumab. It's compared to using Pembrolizumab with a placebo to see if there's any improvement.

Participant Groups

Group I: Phase 3 OBD Arm Experimental Treatment 2 Interventions

ficerafusp alfa OBD + pembrolizumab 200 mg Q3W

Group II: Phase 2 Arm B Experimental Treatment 2 Interventions

ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W

Group III: Phase 2 Arm A Experimental Treatment 2 Interventions

ficerafusp alfa 1500 mg QW + pembrolizumab 200 mg every 3 weeks (Q3W)

Group IV: Phase 2 Arm C Placebo Group 2 Interventions

placebo QW + pembrolizumab 200 mg Q3W

Group V: Phase 3 Arm C Placebo Group 2 Interventions

placebo QW + pembrolizumab 200 mg Q3W

Who Is Running the Clinical Trial?

Bicara Therapeutics

Lead Sponsor

Trials

2

Recruited

940+

Findings from Research

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 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 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]

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 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]

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]

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 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 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]

References

1. 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]

2. England 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. [2021]

3. England 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. [2022]

4. 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]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

7. England 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. [2019]

8. England pubmed.ncbi.nlm.nih.gov

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

9. United States 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. [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]