Ficerafusp Alfa + Pembrolizumab for Head and Neck Cancer

(FORTIFI-HN01 Trial)

Recruiting at 60 trial locations

Overseen By Medical Affairs

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment for individuals with recurrent or metastatic head and neck cancer. The treatment combines two drugs, ficerafusp alfa (an experimental treatment) and pembrolizumab, to determine if they are more effective together than pembrolizumab alone. Participants should have head and neck squamous cell carcinoma (a type of cancer in the mouth, throat, or voice box) that has not recently undergone systemic therapy. The trial aims to assess whether adding ficerafusp alfa to pembrolizumab can safely improve patient outcomes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer therapy.

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.

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

Research shows that patients generally tolerate the combination of ficerafusp alfa and pembrolizumab well. Studies have found that the side effects align with those already known for these drugs, meaning patients have encountered them before. Earlier findings indicate that ficerafusp alfa, used alone or with pembrolizumab, typically has manageable side effects that are not severe. So far, the treatment has shown promise in treating certain types of cancer while maintaining a safety level consistent with past experiences. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ficerafusp alfa combined with pembrolizumab for head and neck cancer because it offers a new mechanism of action compared to traditional treatments. While standard treatments often involve surgery, radiation, or chemotherapy, ficerafusp alfa works by enhancing the immune system's ability to target cancer cells. This approach, combined with pembrolizumab, an immune checkpoint inhibitor, aims to improve the body's natural defenses against cancer. The combination could potentially lead to more effective treatments with fewer side effects, offering hope for better outcomes in managing this challenging condition.

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

Research has shown that the combination of ficerafusp alfa and pembrolizumab holds promise for treating head and neck squamous cell carcinoma (HNSCC). In this trial, participants will receive varying dosages of ficerafusp alfa with pembrolizumab, or a placebo with pembrolizumab. Studies have found that this treatment outperforms the usual care. Specifically, one study reported a confirmed positive response in 31% of patients, including those with HNSCC. Ficerafusp alfa targets two proteins, EGFR and TGF-β, which aid cancer growth. This dual action makes it a strong option for combating this type of cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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

My organs are functioning well.

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

Measurable disease based on RECIST 1.1

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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, 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 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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6017

Ficerafusp alfa with pembrolizumab in patients ... Ficerafusp alfa combined with pembrolizumab continues to show promising efficacy relative to historical data on the current standard of care, particularly in ...

2. onclive.com onclive.com/view/phase-2-3-trial-further-evaluates-ficerafusp-alfa-with-pembrolizumab-in-hpv-head-and-neck-cancer

Phase 2/3 Trial Further Evaluates Ficerafusp Alfa With ... Ficerafusp alfa with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: updated results from an ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06788990

FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or ... This study intends to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab versus placebo with pembrolizumab in 1L PD-L1- ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40643947/

Phase I clinical trial of the bifunctional EGFR/TGF-β fusion ... With combination therapy, 4/13 evaluable patients (31%) had a confirmed response, including one with head and neck squamous cell carcinoma ...

5. ir.bicara.com ir.bicara.com/news-releases/news-release-details/bicara-therapeutics-announces-ficerafusp-alfa-granted

Bicara Therapeutics Announces Ficerafusp Alfa Granted ... Ficerafusp alfa is currently being evaluated in FORTIFI-HN01, a pivotal Phase 2/3 clinical trial in patients with first line (1L) recurrent/ ...

6. onclive.com onclive.com/view/ficerafusp-alfa-pembrolizumab-demonstrates-clinically-meaningful-activity-in-metastatic-hnscc

Ficerafusp Alfa/Pembrolizumab Demonstrates Clinically ... Ficerafusp alfa (BCA101) in combination with pembrolizumab (Keytruda) demonstrated clinically meaningful anti-tumor activity for the first-line treatment of ...