EZABENLIMAB for Anal canal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- 1.\tSigned and dated informed consent,\n- 6.\tLocally advanced disease defined as: •\tStage III (TxN1 or T4N0) Lymph node can be considered positive if one of the following criteria is satisfied: •\tEnlargement (largest short-axis diameter > 1 cm for mesorectal nodes, and > 1.5 cm for other nodes) OR, •\tHeterogeneity or necrosis OR, •\tIrregular contours OR, •\tStrong enhancement at magnetic resonance imaging (MRI) OR, •\tPositivity on positron emission tomography (PET) scan,\n- 7.\tPatient eligible to the mDCF regimen,\n- 8.\tComputed tomography (CT) scan performed within 30 days prior inclusion,\n- 9.\tMRI of pelvis performed within 30 days prior inclusion,\n- 3.\tAbility to comply with the study protocol in the Investigator’s judgment,\n- 10.\tPET scan performed within 30 days prior inclusion,\n- 11.\tAdequate hematologic and end-organ function: defined by the following laboratory test results obtained within 7 days prior to initiation of study treatment:\n- 12.\tSerum albumin  25 g/L (2.5 g/dL),\n- 13.\tFor patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (PTT)  1.5  ULN,\n- 14.\tPatient affiliated to or beneficiary of French social security health insurance system (PUMA; La protection Universelle Maladie).\n- 2.\tAge ≥18 years,\n- 4.\tPerformance status ECOG-WHO ≤ 1,\n- 5.\tHistologically proved squamous cell anal carcinoma,"}

Exclusion criteria

• {"criterion_text":"- 1.\tPreviously received chemotherapy or pelvic radiotherapy,\n- 10.\tInadequate organ functions: uncontrolled cardiac condition, known cardiac failure, unstable coronaropathy, respiratory failure, and chronic obstructive pulmonary disease,\n- 11.\tDiabetes with vascular or neurovascular complications,\n- 12.\tPreexistent peripheral neuropathy or impaired audition,\n- 13.\tHIV positive patient with CD4 count under 400/mm3 (HIV test is mandatory before inclusion),\n- 14.\tActive hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total HBV core antibody (HBcAb) test at screening, are eligible for the study. Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test,\n- 15.\tActive tuberculosis,\n- 16.\tConcomitant treatment with CYP3A4 inhibitor like ritonavir, indinavir, ketoconazole, etc.,\n- 17.\tKnown hypersensitivity or contraindication to any of the study chemotherapy drugs (taxanes, cisplatin, 5-FU, mitomycin, capecitabine) and dihydro pyrimidine dehydrogenase (DPD) complete deficit,\n- 18.\tUncontrolled infection or another life-risk condition,\n- 19.\tKnown hearing impairment that contraindicates cisplatin administration,\n- 2.\tPreviously received anti-tumor immunotherapy (HPV vaccination is allowed),\n- 20.\tAdministration of a (attenuated) live vaccine within 28 days of planned start of study therapy of known need for this vaccine during treatment,\n- 21.\tAdministration of prophylactic phenytoin,\n- 22.\tInadequate laboratory values: MDRD CrCl < 60 ml/min, neutrophil count < 1500/mm3, platelets < 100.000/mm3, bilirubin 2.5 x ULN, AST/ALT 2.5 x ULN,\n- 23.\tPrevious major surgery (requiring general anesthesia) within 28 days of enrollment.\n- 24.\tAny immunosuppressive therapy (i.e. corticosteroids > 10 mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy,\n- 25.\tActive autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed,\n- 26.\tPrior allogeneic bone marrow transplantation or prior solid organ transplantation,\n- 27.\tKnown active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed,\n- 28.\tPreviously received an anti-PD-1, anti-PD-L1, or anti-CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) agent,\n- 29.\tKnown hypersensitivity or allergy to Chinese hamster ovary cell products or any component of Ezabenlimab (BI 754091) formulation,\n- 3.\tMetastatic disease,\n- 30.\tHistory of colorectal inflammatory disease,\n- 31.\tHistory of idiopathic or secondary pulmonary fibrosis (History of radiation pneumonitis in the radiation field fibrosis is permitted), or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy.\n- 32.\tHistory of severe hypersensitivity reactions to other mAbs\n- 33.\tHistory of Chronic colorectal inflammatory disease (Ulcerative colitis, Crohn's disease),\n- 34.\tHistory of connective disease,\n- 35.\tHistory of autoimmune diseases.\n- 4.\tDiagnosis of additional malignancy within 3 years prior to the inclusion date with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer,\n- 5.\tPatient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study,\n- 6.\tCurrent participation in a study of an investigational agent or in the period of exclusion,\n- 7.\tPregnancy, breast-feeding or absence/refusal of adequate contraception for fertile patients during the period of treatment and for 6 months from the last treatment administration; men must refrain from donating sperm during this same period. In addition, men who are sexually active with woman of childbearing potential will be instructed to adhere to contraception for a period of 7 months after the last last treatment administration,\n- 8.\tFemale participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control (i.e., pregnancy rate of less than 1% per year) during the study,\n- 9.\tPatient under guardianship, curatorship, or under the protection of justice."}

Primary endpoints

• {"endpoint_text":"- the Clinical complete response (cCR) 40 weeks from the treatment initiation (the best time to evaluate the local response is 26 weeks from the commencement of standard CRT","definition_or_measurement_approach":"Evaluate the clinical complete response (cCR) rate at week 40 from first DCF cycle, defined as no clinical and radiological sign of residual disease."}

Secondary endpoints

• {"endpoint_text":"- 1.\tMajor pathological response: complete response (pCR)/ near-complete response (pnCR) after induction treatment","definition_or_measurement_approach":"Major pathological response defined as complete response (pCR) or near-complete response (pnCR) after induction treatment."}
• {"endpoint_text":"- 2.\tBiological complete response (bCR) after radiotherapy measured by E6/E7 ctDNA monitoring as previously reported by our team","definition_or_measurement_approach":"bCR measured by E6/E7 HPV ctDNA monitoring (as previously reported by the study team)."}
• {"endpoint_text":"- 1.\tObjective response rate (ORR) evaluated by RECIST criteria v1.1 (Appendix 1). ORR is defined as the addition of complete response (CR) and partial response (PR) rates. Disease control rate is defined as the addition of ORR and SD (stable disease).","definition_or_measurement_approach":"ORR evaluated by RECIST v1.1; ORR = CR + PR. Disease control rate = ORR + SD."}
• {"endpoint_text":"- 2.\tOverall survival (OS). OS is defined as the time between the date of the treatment initiation and death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.","definition_or_measurement_approach":"OS = time from treatment initiation to death from any cause; censoring at last known alive date."}
• {"endpoint_text":"- 3.\tBiological complete response (bCR). bCR is defined as non-detectable HPV ctDNA.","definition_or_measurement_approach":"bCR defined as non-detectable HPV circulating tumor DNA (ctDNA)."}
• {"endpoint_text":"- 4.\tProgression-Free Survival (PFS). PFS is defined as the length of time from the date of treatment inititation to the disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at the last tumor assessment, either during study treatment period or during follow-up period.","definition_or_measurement_approach":"PFS = time from treatment initiation to disease progression or death; censoring at last tumor assessment if no progression."}
• {"endpoint_text":"- 5.\tRecurrence-free survival (RFS) or disease-free survival (DFS). RFS/DFS is defined as the lengh of time from the date of the end of the radiotherapy to local recurrence and/or metastases or death irrespective of cause and censored at the date of last tumor assessment.","definition_or_measurement_approach":"RFS/DFS = time from end of radiotherapy to local recurrence and/or metastases or death; censored at last tumor assessment."}
• {"endpoint_text":"- 6.\tHealth-related Quality of Life (HRQoL) assessment. HRQoL will be assessed by the EORTC QLQ-C30 at baseline, at evaluation visits, at the end of treatment visit, at the end-point visit, and at follow-up visit.","definition_or_measurement_approach":"HRQoL assessed using EORTC QLQ-C30 at specified timepoints (baseline, evaluation visits, end of treatment, end-point visit, follow-up)."}
• {"endpoint_text":"- 7.\tSafety. Safety will be assessed during the study by evaluation of adverse events (AEs) and serious AEs (SAEs), clinical safety laboratory tests, vital signs, and physical examinations according to NCI-CTCAE criteria version 5.0.","definition_or_measurement_approach":"Safety assessed by AEs/SAEs, labs, vitals, physical exams per NCI-CTCAE v5.0."}
• {"endpoint_text":"- 8.\tPET-CT complete response (PET-CR). PET-CR is defined as the absence of pathological hypercaptation. PET-CR will be correlated to cCR, DFS and PFS end-points.","definition_or_measurement_approach":"PET-CR defined as absence of pathological hypercaptation on PET-CT; will be correlated with cCR, DFS and PFS."}

France

Latest Decision Or Authorization Date

26-07-2024

Number Of Sites

13

Number Of Participants

55

Primary sponsor

Full Name

Centre Hospitalier Regional Universitaire

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France