Petosemtamab for Head and Neck Cancer

Recruiting at 200 trial locations

Overseen By Eduardo Pennella, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merus N.V.

Must not be taking: Steroids

Disqualifiers: CNS metastases, Cardiac arrhythmia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called petosemtamab to evaluate its effectiveness for people with head and neck cancer that standard treatments cannot cure. It compares petosemtamab to other treatments selected by doctors for patients whose cancer has spread or returned after other treatments. Individuals with head and neck cancer in areas such as the mouth, throat, or voice box, who have not responded to anti-PD-1 and platinum treatments, might be suitable candidates. As a Phase 3 trial, this study serves as the final step before potential FDA approval, providing patients an opportunity to access a promising new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have any systemic anticancer therapy within 4 weeks of the first dose of the study treatment.

Is there any evidence suggesting that petosemtamab is likely to be safe for humans?

Research has shown that petosemtamab is consistently safe for patients with recurring or spreading head and neck cancer. In earlier studies, patients who received petosemtamab, either alone or with other drugs, generally tolerated the treatment well. Most side effects were manageable and similar to those of other cancer treatments.

These studies noted that while some patients experienced unwanted effects, these were generally expected for this type of treatment. The FDA has recognized petosemtamab as a breakthrough therapy, indicating it shows promise in treating head and neck cancer with an acceptable level of safety.

Overall, current research suggests that petosemtamab is well-tolerated, making it a potential option for those considering joining a clinical trial for treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Unlike the standard treatments for head and neck cancer, which often include surgery, radiation, and chemotherapy, Petosemtamab offers a new approach by specifically targeting cancer cells. This investigational drug works by binding to a unique protein on the surface of cancer cells, potentially blocking their growth and spread more effectively. Researchers are excited because this targeted action might lead to fewer side effects compared to traditional treatments, making it a promising option for patients.

What evidence suggests that petosemtamab might be an effective treatment for head and neck cancer?

Research has shown that petosemtamab, which participants in this trial may receive, may help treat head and neck cancer. In one study, about 37% of patients with head and neck squamous cell carcinoma (HNSCC) responded well to petosemtamab treatment, meaning roughly one-third of the patients saw positive results. Another study found that patients treated with petosemtamab had a median time of 5.3 months before their disease worsened. This suggests that petosemtamab can slow the disease's progression for several months. Overall, these findings support its potential effectiveness in managing HNSCC. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals with head and neck squamous cell carcinoma (HNSCC) who have already undergone treatment but the cancer has returned or spread. Participants should be suitable for second- or third-line therapy, meaning they've tried at least one other treatment that didn't work.

Inclusion Criteria

Signed ICF before initiation of any study procedures

My head or neck cancer worsened after treatment with anti-PD-1 and platinum drugs.

My head or neck cancer is in my throat, mouth, or voice box.

Exclusion Criteria

I have had cancer before, but it was either nonmelanoma skin cancer, cervical pre-cancer, or another type that was treated and is unlikely to come back.

My cancer originates from the nasopharynx.

I do not have brain metastases needing urgent treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either petosemtamab or investigator's choice monotherapy for second- and third-line treatment of incurable metastatic/recurrent HNSCC

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Petosemtamab

Trial Overview The study is testing a new medication called Petosemtamab against a treatment chosen by the investigator, which could be any standard therapy deemed appropriate. It's an open-label study, so everyone knows what treatment they're getting, and it's randomized to compare outcomes fairly.

How Is the Trial Designed?

Group I: MCLA-158 Experimental Treatment 1 Intervention

Group II: Investigator's Choice Active Control 1 Intervention

Petosemtamab is already approved in United States, European Union for the following indications:

Approved in United States as Petosemtamab for:

• None approved yet; Breakthrough Therapy designation for recurrent or metastatic head and neck squamous cell carcinoma

Approved in European Union as Petosemtamab for:

• None approved yet; under investigation for first-line treatment of recurrent or metastatic PD-L1+ head and neck squamous cell carcinoma

Who Is Running the Clinical Trial?

Merus N.V.

Lead Sponsor

Trials

10

Recruited

2,700+

Published Research Related to This Trial

In a meta-analysis of seven randomized controlled trials, cetuximab combined with radiotherapy resulted in significantly poorer overall survival and locoregional control compared to cisplatin combined with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC).

While cetuximab showed inferior efficacy, the overall incidence of severe adverse events was similar between the cetuximab and cisplatin treatment groups, indicating that cetuximab may not provide a safety advantage despite its reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials. Li, Y., Yang, C., Gan, Y., et al.[2023]

In a phase I study involving 19 patients with advanced squamous cell carcinoma of the head and neck, the combination of panitumumab, carboplatin, and escalating doses of paclitaxel with intensity-modulated radiotherapy (IMRT) showed a high overall complete clinical response rate of 95%.

The treatment was generally well tolerated, with the maximum tolerated dose of paclitaxel identified at 30 mg/m², although all patients experienced significant side effects like mucositis and oral pain, indicating the need for careful management of these toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck. Wirth, LJ., Allen, AM., Posner, MR., et al.[2020]

In head and neck squamous cell carcinoma (HNSCC), CD155 and PD-L1 are highly co-expressed on myeloid-derived suppressor cells (MDSCs), which negatively impacts T cell activity and tumor immunity.

Combining treatments that block both TIGIT/CD155 and PD-1/PD-L1 signaling significantly inhibited tumor growth in mouse models, improved T cell responses, and suggested a promising strategy to enhance the effectiveness of existing PD-L1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIGIT/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells. Mao, L., Xiao, Y., Yang, QC., et al.[2022]

In a trial involving 46 patients with high-risk, resected head and neck squamous cell carcinoma, the combination of the monoclonal antibody panitumumab with cisplatin chemoradiotherapy showed a promising 2-year progression-free survival rate of 70%.

The treatment was found to be tolerable, with 32% of patients experiencing severe toxicities, indicating that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer. Ferris, RL., Geiger, JL., Trivedi, S., et al.[2020]

In a study of 59 patients with recurrent or metastatic head and neck cancer treated with weekly cetuximab and paclitaxel, the median progression-free survival was 5.7 months and the median overall survival was 11.8 months, indicating a potential benefit of this treatment regimen.

Patients who had previously received cetuximab experienced shorter progression-free and overall survival, suggesting that prior treatment may negatively impact the effectiveness of the Cmab-PTX combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly Cetuximab and Paclitaxel for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Fushimi, C., Baba, D., Masubuchi, T., et al.[2021]

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]

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 18 patients with recurrent metastatic head and neck squamous cell carcinoma, the combination of cetuximab and paclitaxel after immune checkpoint inhibitor therapy showed a 44.4% objective response rate and a 72.2% disease control rate, indicating significant efficacy.

The treatment was associated with manageable safety, with some patients experiencing grade 3 adverse events like neutropenia, but no treatment-related deaths occurred, suggesting that this regimen is a viable option for patients who have progressed after ICI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Suzuki, S., Toyoma, S., Kawasaki, Y., et al.[2021]

In a study of 46 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of weekly paclitaxel and cetuximab showed a promising overall response rate of 54%, with 22% achieving complete responses.

The treatment was well tolerated, with a disease control rate of 80% and median overall survival of 8.1 months, making it a potential option for patients who cannot receive platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Hitt, R., Irigoyen, A., Cortes-Funes, H., et al.[2022]

In a study of 22 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab, 59.1% achieved disease control, indicating that this PD-1 targeting therapy can provide clinical benefits for some patients.

Pembrolizumab was generally well-tolerated, with only mild adverse effects reported, such as immune-related pneumonitis and skin rashes, suggesting it is a safe option for patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for recurrent/metastatic head and neck squamous cell carcinoma in an Asian population. Chen, WC., Chu, PY., Lee, YT., et al.[2021]

The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) showed a response rate of 64% in patients at dose level I and 78.3% at dose level II, indicating significant efficacy in treating squamous cell carcinoma of the head and neck (SCCHN).

The treatment was associated with manageable safety concerns, with dose-limiting toxicities including renal toxicity and nausea, and the maximum tolerated dose was reached at level II, suggesting that dose level I is safer and recommended for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. Schrijvers, D., Van Herpen, C., Kerger, J., et al.[2020]

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 the CheckMate 651 trial involving 947 patients with recurrent/metastatic squamous cell carcinoma of the head and neck, nivolumab plus ipilimumab did not significantly improve overall survival compared to the EXTREME regimen, with median survival times of 13.9 months versus 13.5 months, respectively.

However, nivolumab plus ipilimumab demonstrated a much better safety profile, with only 28.2% of patients experiencing severe treatment-related adverse events compared to 70.7% in the EXTREME group, highlighting its potential as a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651. Haddad, RI., Harrington, K., Tahara, M., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6024

Petosemtamab (MCLA-158) with pembrolizumab as first- ... Results: A total of 45 pts were treated; as of a September 16, 2024 data cutoff, 18 pts continuing on therapy. Median age was 64 years (range 23 ...

2. ir.merus.nl ir.merus.nl/news-releases/news-release-details/merus-interim-data-petosemtamab-metastatic-colorectal-cancer

Merus' Interim Data on Petosemtamab in Metastatic ... “These data demonstrate petosemtamab's clinical activity beyond head and neck squamous cell carcinoma. We are encouraged that petosemtamab ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04490-9/fulltext

411MO Petosemtamab (MCLA-158) monotherapy in ... A single-arm cohort of petosemtamab monotherapy (1500 mg every 2 weeks) in 2L+ HNSCC previously reported a 37.2% overall response rate (ORR) with a median ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12110399/

Petosemtamab, a Bispecific Antibody Targeting Epidermal ... This review also discusses the unique mechanisms of action of petosemtamab as well as promising early clinical results in the treatment of head ...

5. onclive.com onclive.com/view/petosemtamab-receives-fda-breakthrough-therapy-designation-in-pretreated-hnscc

Petosemtamab Receives FDA Breakthrough Therapy ... The median progression-free survival in the efficacy-evaluable population, with 14 patients censored, was 5.3 months (95% CI, 3.7-6.8). Notably, ...