Phase II Study of Ficerafusp Alfa and Nivolumab in Patients with Platinum-Refractory Head and Neck Squamous Cell Carcinoma Progressing Within 6 Months of Multimodal Therapy
- Trial ID
- 2025-521437-88-00
- Protocol
- GORTEC 2025-01
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the objective response rate (ORR) in patients with platinum-refractory head and neck squamous cell carcinoma (HNSCC) who experienced disease progression within 6 months of multimodal curative treatment when receiving ficerafusp alfa in combination with nivolumab compared to nivolumab monotherapy. 5 Secondary objectives include:
- Comparison of the duration of response between the study arms.
- Evaluation of progression-free survival (PFS).
- Assessment of overall survival (OS).
- Comparison of treatment compliance between arms.
- Evaluation of adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with head and neck squamous cell carcinoma. Eligible participants are aged between 18 and 75 years and possess an Eastern Cooperative Oncology Group performance status of 0 or 1. The study focuses on individuals with histologically or cytologically confirmed disease located in the oral cavity, larynx, hypopharynx, or oropharynx. Inclusion requires platinum refractory disease characterized by local, regional, or metastatic progression within 6 months following a multimodal curative treatment strategy. For patients with oropharyngeal squamous cell carcinoma, a p16 negative status must be confirmed. Participants must present with measurable tumor lesions as assessed by computed tomography or magnetic resonance imaging according to RECIST v 1.1.
Plans and Procedures
This phase II clinical trial is designed to evaluate the efficacy of ficerafusp alfa in combination with nivolumab compared to nivolumab monotherapy in patients with platinum-refractory head and neck squamous cell carcinoma. The primary endpoint is the objective response rate, defined as the proportion of patients achieving a confirmed complete response or partial response according to RECIST v1.1. Secondary endpoints include duration of response, progression-free survival, overall survival, and the incidence of adverse events graded by NCI-CTCAE v5.0. The study involves a screening process to confirm histologically or cytologically confirmed squamous cell carcinoma of the head and neck, specific tumor locations, and disease progression within 6 months of multimodal therapy. Participants must demonstrate measurable tumor lesions via CT scan or MRI and meet specific p16 status requirements for oropharyngeal squamous cell carcinoma. The trial is estimated to be conducted between December 2025 and December 2029.
Treatment
The experimental treatment consists of ficerafusp alfa, provided as a vial for intravenous use. This solution for injection is administered at a dose of 1500 mg via the intravenous route.
The comparator treatment is nivolumab, supplied as an OPDIVO 10 mg/mL concentrate for solution for infusion. This solution for infusion is administered at a dose of 240 mg.
Efficacy
The primary efficacy assessment is the objective response rate (ORR), which is defined as the proportion of patients achieving a confirmed best overall response (BOR) consisting of either a complete response (CR) or a partial response (PR). These responses are determined by the investigator in accordance with RECIST v1.1.
Secondary efficacy and safety parameters include:
- Duration of response (DOR), measured as the interval from the first occurrence of CR or PR to the time of disease progression or death.
- Progression-free survival (PFS), defined as the time from randomization or the start of the run-in phase to the first radiographic documentation of progression via RECIST v1.1 or death from any cause.
- Overall survival (OS), defined as the time from randomization or the start of the run-in phase to death from any cause or the date of the last follow-up.
- The incidence and severity of adverse events, serious adverse events, and laboratory abnormalities, graded according to the NCI-CTCAE v5.0.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient is >18 years, ≤75 years of age on the day the ICF is signed.
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Histologically or cytologically confirmed squamous cell carcinoma of head and neck (HNSCC). Eligible primary tumor locations are oral cavity, larynx hypopharynx, or oropharynx (OPSCC).
- Local, regional or metastatic progression within 6 months after the last dose of platinum in a multimodal strategy for locally advanced stage, not amenable to salvage surgery in case of local or regional progression. Specification regarding inclusion criterion no. 05 : The pProgression is not assessed as per RECIST. and Any of the following that will be considered as a progression any of the following items : o A positive biopsy 3 months after the end of radiotherapy given with curative intent o Appearance of any new lesion (exe.g.: metastases or lymph nodes) o Any increase in tumor size o Any persisting tumor (confirmed with a biopsy) not amenable to salvage surgery
- For OPSCC patients, a pathological report determination of human papillomavirus (HPV) status by p16 expression must be p16 negative
- Measurable tumor lesion(s) assessed by H&N-computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on RECIST v 1.1 (see Appendix 3). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated.
Exclusion Criteria
- Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity or salivary gland, thyroid or parathyroid gland pathologies, skin, squamous cell carcinoma of unknown primary or non-squamous histologies (e.g., mucosal melanoma).
- Subjects having received prior systemic treatment for metastatic or recurrent disease
- Subjects having received prior treatment with anti-EGFR antibody.
- Subjects having received prior treatment with anti-TGF-β therapy.
- Subjects having received prior therapy with anti-PD1, anti-PD-L1 (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- Patient who participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (whichever is shorter) following prior therapy or at least 4 weeks if half live of the agent received is not known before enrollment.
- Known to be diagnosed and/or treated for any other additional malignancy within 2 years prior to registration/randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer defined as follows: Stage T1 up to T2a with a Gleason score ≤6 and prostatic specific antigen <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to registration/randomization. Other exceptions may be considered with the Sponsor’s consultation. The time requirement for no malignancy for 2 years does not apply to the cancer for which a patient is enrolled in the study
- Any of the following <6 months before starting study treatment: ST-elevation myocardial infarction, severe/unstable angina, uncontrolled cardiac ventricular arrythmia, coronary/peripheral artery bypass graft or stent, cerebrovascular accident/stroke less than 6 months prior to enrollment or NYHA Class III/IV congestive heart failure. Subjects with deep vein thrombosis who are hemodynamically stable can enroll if they are on a stable dose of anticoagulants for at least 3 months
- Serious systemic infection (bacterial, viral, or fungal) within 4 weeks before first dose of study treatment, or active systemic infection requiring either hospitalization or parenteral anti-infective therapy within 2 weeks before first dose of study treatment.
- History of (non-infectious) pneumonitis/ interstitial lung disease or has current pneumonitis/ Interstitial lung disease.
- Active central nervous system (CNS) metastases or carcinomatous meningitis. Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded. Patients with a history of treated central nervous system metastases (by surgery or radiation therapy) may be eligible if central nervous system metastases have been stable for at least 4 weeks, i.e., without evidence of progression by repeat imaging and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- History of uncontrolled seizures, CNS disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 15 Dec 2025 | 121 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Ficerafusp Alfa | Test | VIAL FOR INTRAVENOUS USE | SOLUTION FOR INJECTION | 1500 | 60 | PRD12408372 |
OPDIVO 10 mg/mL concentrate for solution for infusion. | Comparator | CONCENTRATE FOR SOLUTION FOR INFUSION | SOLUTION FOR INFUSION | 240 | 48 | PRD2941372 |