Combination Immunotherapy + Chemotherapy for Head and Neck Cancer

Not currently recruiting at 46 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must be taking: Cetuximab

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a mix of medications can shrink tumors in people with head and neck cancer when other treatments haven't worked or aren't available. The trial uses a combination of medicines, including BI 765063 and Ezabenlimab (both immunotherapies), which help the immune system fight cancer and block the tumor's growth signals. Participants will receive these treatments as infusions, with regular health checks to monitor progress. This trial suits individuals who have tried platinum-based chemotherapy but still experience recurring or spreading cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance 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 your specific situation with the trial doctors to get a clear answer.

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

Research has shown that the combination of BI 765063, ezabenlimab, and cetuximab is generally safe for treating head and neck cancer. These treatments are antibodies that help the immune system fight cancer. Cetuximab blocks signals that promote tumor growth. Studies have found that this combination is usually well-tolerated.

In another treatment group, BI 765063 and ezabenlimab are combined with chemotherapy, which also has a manageable safety profile.

In a different group, BI 765063, ezabenlimab, and another antibody, BI 836880, are used together. BI 836880 prevents the formation of new blood vessels, which the cancer needs to grow. Early research suggests this combination is generally safe as well.

Overall, these treatments have shown few serious side effects in studies so far. Participants receive regular monitoring to ensure the treatment remains safe for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 765063 and ezabenlimab for head and neck cancer because they offer a fresh approach compared to traditional treatments like surgery, radiation, and chemotherapy. Most treatments for this cancer type focus on directly attacking the tumor, but BI 765063 and ezabenlimab work differently. They enhance the body's immune response by targeting the SIRPα protein, which plays a role in immune suppression. This novel mechanism of action could potentially make the immune system more effective against cancer cells, offering hope for patients who have not responded well to existing therapies.

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

Research has shown that combining BI 765063, ezabenlimab, and cetuximab holds promise for treating head and neck cancer. In this trial, one cohort will receive this combination to help the immune system fight cancer and block signals that allow tumor growth. Studies have found that this combination can shrink tumors and is generally well-tolerated by patients. Cetuximab, in particular, stops tumor growth by blocking specific signals. This combination approach is designed to attack cancer in various ways, potentially improving treatment success. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults with head and neck or liver cancer, for whom previous treatments failed or no standard treatment is available. Participants must be over 18, have a life expectancy of at least 3 months, and able to perform daily activities with little assistance (ECOG status 0-1). They should not have other active cancers or severe autoimmune diseases requiring systemic treatment. Women who can bear children must use effective contraception.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Expected life expectancy of at least 3 months.

I agree to provide required biopsy samples before and during treatment.

Exclusion Criteria

I haven't had any active cancer other than the one for this trial in the last 5 years, except for certain skin cancers or cervical cancer that were treated.

I haven't had any severe bleeding or blood clot events in the last year.

I have had severe reactions to antibody treatments before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 765063, ezabenlimab, and cetuximab as infusions. Treatment continues as long as participants benefit and can tolerate it, up to 2 years.

Up to 104 weeks

Infusions every 1-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 765063
• BI 836880
• Cetuximab
• Ezabenlimab
• Investigator´s Choice Chemotherapy

Trial Overview The trial tests combinations of BI 765063, Ezabenlimab (both immune system boosters), Cetuximab (growth signal blocker), BI 836880 (blocks blood vessel formation in tumors), and chemotherapy. Patients receive infusions every few weeks and are monitored for tumor shrinkage while assessing the tolerability of the treatments.

How Is the Trial Designed?

Group I: Cohort E: BI 765063 + ezabenlimab + BI 836880 Experimental Treatment 3 Interventions

30 SIRPα V1/V1 homozygous patients with advanced or metastatic 2nd line HCC who progressed on therapy with atezolizumab in combination with bevacizumab.

Group II: Cohort D: BI 765063 + ezabenlimab + BI 836880 Experimental Treatment 3 Interventions

30 SIRPα V1/V1 homozygous patients with advanced or metastatic 1st line HCC.

Group III: Cohort C: BI 765063 + ezabenlimab Experimental Treatment 2 Interventions

30 SIRPα V1/V1 homozygous patients with advanced or metastatic 1st line Hepatocellular Carcinoma (HCC).

Group IV: Cohort B: BI 765063 + ezabenlimab + chemo (invest choice) Experimental Treatment 3 Interventions

30 SIRPα V1/V1 homozygous patients with 2nd line recurrent/metastatic HNSCC who had received prior platinum-based therapy within the recurrent/metastatic setting.

Group V: Cohort A: BI 765063 + ezabenlimab + cetuximab Experimental Treatment 3 Interventions

30 Signal Regulatory Protein Alpha (SIRPα) V1/V1 homozygous patients with 2nd line recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) who had received prior platinum-based therapy within the recurrent/metastatic setting.

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

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]

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 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]

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]

PD-1 inhibitors significantly improve overall survival in patients with recurrent or metastatic head and neck cancer compared to standard treatments, with a relative risk of death reduced by 40%.

Patients with human papillomavirus (HPV) positive head and neck cancer showed better response rates to PD-1/PD-L1 inhibitors than those who are HPV negative, indicating that HPV status may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. Wang, BC., Cao, RB., Li, PD., et al.[2021]

In a study of 22 patients with resectable locally advanced head and neck squamous cell carcinomas, the combination of pembrolizumab and chemotherapy resulted in a postoperative pathological complete response (pCR) rate of 36.4%, indicating significant efficacy as a neoadjuvant treatment.

The treatment did not adversely affect surgical safety, with a high rate of laryngeal function preservation at 90.9%, and no delays to surgery due to adverse drug reactions, although delayed wound healing was noted in 22.7% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas. Wang, K., Gui, L., Lu, H., et al.[2023]

Neoadjuvant immunotherapy targeting the PD-1/PD-L1 axis in head and neck cancer has shown a favorable overall objective response rate of 45.9% across eight clinical trials involving 260 patients.

Importantly, there were no deaths reported due to immune-related toxicities, indicating that this treatment approach is not only effective but also safe in the neoadjuvant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. Amin, N., Maroun, CA., El Asmar, M., et al.[2022]

In a study of 14 heavily pretreated patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), the combination of pembrolizumab and lenvatinib showed an objective response rate of 28.6%, indicating potential efficacy even in patients who had previously failed anti-PD-1 therapy.

The disease control rate was 42.9%, with an overall survival of 6.2 months and progression-free survival of 4.6 months, suggesting that this combination therapy may provide meaningful benefits for patients who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer. Chen, TH., Chang, PM., Yang, MH.[2021]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

Patients with advanced head and neck cancer who had no pre-existing comorbidities experienced significantly longer overall survival and progression-free survival when treated with immunotherapy, indicating that comorbidities negatively impact treatment outcomes.

Interestingly, while patients without comorbidities had better survival rates, they also faced a higher risk of immune-related adverse events (irAEs), suggesting a complex relationship between health status and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy. Guller, M., Cooper, DJ., Alkhatib, H., et al.[2023]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6019

An open-label, phase Ib trial of the SIRPα inhibitor BI ... BI 765063 in combination with ezabenlimab and cetuximab has a manageable safety profile and promising efficacy as second-line treatment in pts with R/M HNSCC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05249426

NCT05249426 | A Study to Test Whether Different ... BI 765063 and ezabenlimab may help the immune system fight cancer (checkpoint inhibitors). Cetuximab blocks growth signals and may prevent the tumour from ...

3. boehringer-ingelheim.com boehringer-ingelheim.com/science-innovation/human-health-innovation/new-study-data-sirpa-inhibitors

New study data for SIRPα inhibitors BI 765063 in combination with programmed cell death-1 (PD1) inhibitor antibody ezabenlimab + cetuximab demonstrated a well-tolerated safety ...

4. researchgate.net researchgate.net/publication/392303366_An_open-label_phase_Ib_trial_of_the_SIRPa_inhibitor_BI_765063_in_combination_with_the_PD-1_inhibitor_ezabenlimab_and_cetuximab_in_patients_pts_with_head_and_neck_squamous_cell_carcinoma

An open-label, phase Ib trial of the SIRPα inhibitor BI ... Conclusions: These preliminary data indicate that BI 765063 in combination with ezabenlimab and cetuximab has a manageable safety profile and promising efficacy ...

5. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2025.43.16_suppl.6019

An open-label, phase Ib trial of the SIRPa inhibitor BI ... Conclusions: These preliminary data indicate that BI 765063 in combination with ezabenlimab and cetuximab has a manageable safety profile and promising efficacy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05249426

NCT05249426 | A Study to Test Whether Different ... BI 765063 and ezabenlimab may help the immune system fight cancer (checkpoint inhibitors). Cetuximab blocks growth signals and may prevent the tumour from ...

7. ose-immuno.com ose-immuno.com/wp-content/uploads/2021/10/EN_210520_ASCO_BI765063_VF.pdf

BI 765063, a first-in-class SIRPα inhibitor on the ... • Data indicate BI 765063 was well tolerated and showed ... Title: “Safety, pharmacokinetics, efficacy, and preliminary biomarker data of first-in class.