A phase 3, open-label, randomized, controlled study to evaluate the efficacy and safety of MCLA-158-CL02 versus investigator’s choice of monotherapy in patients previously treated for incurable, metastatic, or recurrent squamous cell carcinoma of the head and neck

PI: Prof.ssa Lisa Licitra 

The MCLA-158-CL02 study is a clinical trial evaluating the safety and activity of Petosemtamab compared to the best investigator-chosen monotherapy for the treatment of patients with locally recurrent and/or metastatic squamous cell carcinoma of the head and neck who have previously been treated with an anti-PD(L)1 [Programmed Cell Death Protein 1] immunotherapy and platinum-based chemotherapy. 

Petosemtamab is a bispecific antibody that targets two proteins: EGFR (Epidermal Growth Factor Receptor) and LGR5 (Leucine-rich repeat-containing G-protein coupled Receptor 5). As a biological drug, it blocks the EGFR receptor, inhibiting tumor cell growth and progression, and instead promoting apoptosis, or programmed cell death. Petosemtamab also specifically targets LGR5, a critical marker involved in the regulation of stem cell proliferation and differentiation, essential for tissue regeneration. The LGR5 protein is overexpressed (abnormally high expression) in solid tumors and is altered in various cancer types. 

The study, conducted in accordance with international ethical guidelines, is considered experimental, as Petosemtamab is not yet approved by health regulatory authorities for the treatment of head and neck cancer. However, the potential impact of Petosemtamab has already been demonstrated in previous clinical studies, supporting the biological and clinical rationale that this treatment may improve the prognosis in this patient setting. 

By contrast, Cetuximab, Methotrexate, and Docetaxel are drugs that have long been approved by the Food and Drug Administration (FDA) in the United States and by AIFA (Agenzia Italiana del Farmaco) for the treatment of head and neck cancer. 

The goal of this study is therefore to achieve higher oncologic response rates with the investigational drug Petosemtamab compared to standard therapy chosen by the investigator, as well as to improve progression-free survival and overall survival in patients with local and/or distant recurrence previously treated with immunotherapy and platinum-based therapy. 

This is an open-label, randomized study.   

The term "open-label" means that the patient, the physician, and the study staff all know which study drug is being administered.   

The term "randomized" means that the drugs included in the study will be selected randomly, like flipping a coin. Assignment to one treatment arm or the other will occur through a computerized process called "randomization," which randomly assigns treatment without any input from the investigator or patient. There will be a 50% chance of being assigned to the experimental arm and a 50% chance of being assigned to the control arm: 

- Experimental arm: involves administration of Petosemtamab via intravenous infusion every 2 weeks, preceded by appropriate anti-allergic premedication; 

-Control arm: involves administration of cetuximab, methotrexate, or docetaxel (based on the investigator’s decision), via weekly intravenous infusions, with dosages potentially increasing over time. 

Eligibility for enrollment in the study depends on patient characteristics (demographic data, oncologic history, and comorbidities), laboratory tests, and radiological parameters, which will be evaluated through specific screening tests prior to treatment initiation. These assessments will be carried out at this institution and follow clearly defined timelines. 

Patients will be monitored not only for oncologic response but also for adverse effects caused by the biological therapies Petosemtamab or Cetuximab, as well as by chemotherapy-related toxicities. It is possible that treatment may cause side effects, often already known, which will require symptomatic treatment and targeted strategies to reduce the intensity of these adverse effects (e.g., treatment breaks, dose reductions, etc.). To ensure patient safety regarding treatment toxicity, participants in the study will be closely monitored. 

Treatment will continue until maximum response is reached and will follow specific timelines and procedures as required by the protocol. However, treatment will be discontinued in the case of disease progression, unacceptable toxicity, or—as is always the case in clinical trials—based on the decision of the investigator and/or the patient (who will still continue to have access to medical care and will not lose any legal rights or benefits to which they are entitled). 

The staff involved in the study remains available for more detailed information (email: amo@istitutotumori.mi.it).