BI 770371 + Pembrolizumab ± Cetuximab for Head and Neck Cancer

Recruiting at 84 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Anticonvulsants, Corticosteroids, Chemotherapy, others

Disqualifiers: Nasopharyngeal carcinoma, Brain metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 27 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining different medicines can shrink tumors in people with head and neck cancer. It tests three medicines: BI 770371 (an experimental treatment) and pembrolizumab, designed to boost the immune system's ability to fight cancer, and cetuximab, which may stop tumors from growing. Participants are divided into three groups, each receiving a different combination of these medicines through an IV. This trial suits those with head and neck cancer that has spread or returned and who have not received other systemic therapies. Regular checks will monitor tumor size and overall health throughout the study.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients who have received certain cancer treatments in the past may not be eligible. It's best to discuss your specific medications with the trial team.

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

A previous study found pembrolizumab safe for head and neck cancer, with manageable side effects. It is often used alongside other treatments. Research shows that while pembrolizumab can cause side effects, it is generally considered safe. Another study found that combining pembrolizumab with BI 770371 did not lead to unexpected safety issues.

Cetuximab, when combined with other cancer drugs, can block signals that promote tumor growth. While the safety of BI 770371 is still under investigation, pembrolizumab is already approved for other uses, suggesting it is generally safe for patients. Overall, these treatments are closely monitored in trials to ensure they are well-tolerated. Participants' health is regularly checked to detect any unwanted effects early. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they offer new ways to target the disease. Pembrolizumab is already known for boosting the immune system to fight cancer cells, but combining it with BI 770371 and Cetuximab opens up new possibilities. BI 770371 is believed to enhance the effectiveness of pembrolizumab by targeting specific cancer pathways, while Cetuximab helps block growth signals in cancer cells. This combination approach could provide more effective treatment options compared to standard therapies, potentially improving outcomes for patients.

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

Research has shown that pembrolizumab effectively treats head and neck cancer. The KEYNOTE-048 study demonstrated that pembrolizumab benefited patients with recurring or spreading head and neck cancer. In this trial, some participants will receive pembrolizumab alone, while others will receive pembrolizumab combined with BI 770371, which aims to strengthen the immune system to fight cancer. Another group will receive pembrolizumab, BI 770371, and cetuximab, which may help stop tumors from growing by blocking signals that promote growth. These treatments are being tested to determine their effectiveness in shrinking tumors and preventing their spread. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with head and neck cancer are eligible for this trial. Participants must have a type of cancer that responds to the study medicines. They should be able to receive infusions and commit to regular health checks and tumor assessments.

Inclusion Criteria

I can safely receive cetuximab treatment according to local guidelines.

Presence of at least one measurable non-Central nervous system (CNS) lesion (according to RECIST v1.1)

Willingness to provide pretreatment (baseline) biopsy / tissue to the sponsor (fresh or archival one). A recent biopsy (<3 months) is preferred, however an archival biopsy up to 12 months prior to screening could be accepted. If these requirements cannot be met, then the patient may be allowed to enter the study at Sponsor discretion, after agreement between the Investigator and Sponsor

Exclusion Criteria

I have had a stem cell or organ transplant.

My cancer is in the nasal area or nearby and its origin is unknown.

My doctor prefers chemotherapy or a combo treatment over pembrolizumab for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive study medicines (BI 770371, pembrolizumab, and/or cetuximab) as an infusion into a vein. Participants are put into 3 groups randomly, and doctors regularly check the size of the tumor and participants' health.

Up to 27 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival assessments.

Up to 27 months

What Are the Treatments Tested in This Trial?

Interventions

• BI 770371
• Cetuximab
• Pembrolizumab

Trial Overview The trial is testing if combining BI 770371 with Pembrolizumab, with or without Cetuximab, is more effective than Pembrolizumab alone in shrinking tumors. Patients will be randomly assigned into three groups to receive different medicine combinations via vein infusion.

How Is the Trial Designed?

Group I: Pembrolizumab + BI 770371 + Cetuximab Experimental Treatment 3 Interventions

Group II: Pembrolizumab + BI 770371 Experimental Treatment 2 Interventions

Group III: Pembrolizumab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

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 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 involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06806852

NCT06806852 | A Study to Test Whether Treatment With BI ... BI 770371 and pembrolizumab may help the immune system fight cancer. Cetuximab blocks growth signals and may prevent the tumor from growing. Participants are ...

2. withpower.com withpower.com/trial/bi-770371-pembrolizumab-cetuximab-for-head-and-neck-cancer-8086b

BI 770371 + Pembrolizumab ± Cetuximab for Head and ... The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219809/

Updated Results of the Phase III KEYNOTE-048 Study - PubMed Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT06806852

A Study to Test Whether Treatment With BI 770371 in ... Impact Score 6A Study to Test Whether Treatment With BI 770371 in Combination With Pembrolizumab With or Without Cetuximab Helps People With Head and Neck ...

5. annalsofoncology.org annalsofoncology.org/issue/S0923-7534(25)X0011-9?pageStart=29

September 2025 1449eP Survival benefit of curative therapy in functionally frail head and neck cancer patients: A real-world tertiary center experience.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e14593

Safety of pembrolizumab in advanced head and neck ... Pembrolizumab is associated with a higher risk of AEs in patients with advanced HNSCC compared to the control group.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The aim of the review was to systematically review real-world data on the effectiveness and safety of pembrolizumab in recurrent/metastatic/ ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified. (Funded by Merck Sharp ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01277-8/fulltext

P110-7 Efficacy and safety of pembrolizumab in recurrent ... Conclusions. Pembrolizumab therapy for recurrent or metastatic head and neck cancer was effective and has a good safety profile.

10. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1160144/full

Real-world treatment patterns and outcomes among ... The pembrolizumab monotherapy group had a median (95% CI) rwOS of 12.1 (9.2–15.1) months, rwToT of 4.2 (3.5–4.6) months, and rwTTNT of 6.5 (5.4–7.4) months.