Petosemtamab for Head and Neck Cancer

Recruiting at 95 trial locations

Overseen By Eduardo Pennella, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Merus N.V.

Must not be taking: Steroids

Disqualifiers: CNS metastases, Cardiac arrhythmia, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a phase 3 open-label, randomized, controlled, multicenter study to compare petosemtamab vs investigator's choice monotherapy in HNSCC patients for the second- and third-line treatment of incurable metastatic/recurrent disease.

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.

What data supports the idea that Petosemtamab for Head and Neck Cancer (also known as: Petosemtamab, MCLA-158) is an effective treatment?

The available research does not provide specific data on Petosemtamab for Head and Neck Cancer. Instead, it discusses other treatments like panitumumab, nivolumab plus ipilimumab, and pembrolizumab. For example, pembrolizumab showed a disease control rate of 59.1% in patients with recurrent/metastatic head and neck cancer. However, there is no direct comparison or data available for Petosemtamab in the provided information. ^{1 2 3 4 5}

What safety data is available for Petosemtamab (MCLA-158) in head and neck cancer treatment?

The provided research does not contain specific safety data for Petosemtamab (MCLA-158) in head and neck cancer treatment. The studies focus on other treatments and their safety profiles, such as PD-1/PD-L1 inhibitors, docetaxel, cisplatin, 5-fluorouracil, cetuximab, and paclitaxel. Further research specifically on Petosemtamab (MCLA-158) is needed to determine its safety profile. ^{6 7 8 9 10}

Is the drug Petosemtamab a promising treatment for head and neck cancer?

The information provided does not directly mention Petosemtamab or its effectiveness for head and neck cancer, so we cannot determine if it is a promising treatment based on the given research articles. ^{4 5 11 12 13}

Eligibility Criteria

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

I am 18 years old or older.

Signed ICF before initiation of any study procedures

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Petosemtamab (Monoclonal Antibodies)

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.

Participant Groups

Group I: MCLA-158 Experimental Treatment 1 Intervention

Group II: Investigator's Choice Active Control 1 Intervention

Who Is Running the Clinical Trial?

Merus N.V.

Lead Sponsor

Trials

10

Recruited

2,700+

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

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 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 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 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

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. [2020]

2. United States 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. [2023]

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

Pembrolizumab for recurrent/metastatic head and neck squamous cell carcinoma in an Asian population. [2021]

4. England 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. [2020]

5. Germany 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. [2023]

6. United States 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. [2021]

7. England 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. [2020]

8. Switzerland 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. [2021]

9. England 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. [2022]

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

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy. [2023]

11. Greece pubmed.ncbi.nlm.nih.gov

Weekly Cetuximab and Paclitaxel for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2021]

12. England 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. [2022]

13. 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]