Phase II Study of Cemiplimab Before and After Standard Chemoradiotherapy in Patients With Locally Advanced Cervical Carcinoma
- Trial ID
- 2025-521839-36-00
- Protocol
- CADILLACC TRIAL
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the antitumor activity of cemiplimab administered before and after standard chemoradiotherapy in patients with locally advanced cervical carcinoma. This is assessed by the objective response rate, defined as the percentage of participants achieving a complete response or partial response according to RECIST1.1 criteria at the end of maintenance treatment. 5
Secondary objectives include the assessment of:
- Progression-free survival and overall survival in the total population and in participants with high PD-L1 expression (PD-L1≥50%).
- Duration of response and complete pathological response at the end of the induction and maintenance phases.
- Time to symptom progression and progression-free survival 2 following the discontinuation of study treatment.
- Incidence of local progression, distant disease progression, and secondary malignancy.
- Safety and tolerability profile of the treatment. 4
- Quality of life, including global health status, physical function, and symptom experience using EORTC QLQ-C30, EORTC CX24, and EQ-5D-5L instruments.
- The immune response to the integrated immunotherapy regimen.
Participants
The sponsor did not provide the total number of participants. The study population consists of female patients older than 18 years diagnosed with locally advanced cervical carcinoma, specifically classified as FIGO 2018 stage IB3-IVA. Eligible participants must have histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix with PD-L1 positive tumors (PD-L1 ≥1%). Inclusion requires patients to be immunotherapy-naïve and have not previously received definitive surgical, radiation, or systemic therapy for cervical cancer. Participants must present with measurable disease according to RECIST 1.1 and maintain an ECOG performance status of 0 or 1. Necessary physiological requirements include adequate hematological function, renal function, and hepatic function. A life expectancy of at least 3 months is required, and participants must not be pregnant or breastfeeding.
Plans and Procedures
This Phase II clinical trial is designed to evaluate the antitumor activity of cemiplimab in patients diagnosed with locally advanced cervical carcinoma. The study methodology involves the administration of cemiplimab both before and after standard chemoradiotherapy, which includes cisplatin administered via intravenous infusion. The primary objective is to determine the objective response rate, defined as the percentage of participants achieving a complete response or partial response according to RECIST 1.1 criteria at the conclusion of maintenance treatment. Secondary endpoints include progression-free survival, overall survival, and the duration of response. The trial includes a screening process to confirm eligibility based on PD-L1 expression, histological confirmation of carcinoma, and adequate hematological, renal, and hepatic function. The estimated duration of the study period for recruitment and follow-up extends from 2026 to 2032.
Treatment
The experimental treatment consists of cemiplimab, provided as a concentrate for solution for infusion. The administered dose is 350 mg via intravenous infusion.
The background therapy includes cisplatin, administered as a solution for infusion. The dosage is 40 mg/m² through intravenous infusion. This substance is utilized as part of the standard chemoradiotherapy regimen for locally advanced cervical carcinoma.
Efficacy
The primary efficacy endpoint is the objective response rate (ORR), which is determined as the percentage of participants achieving a complete response (CR) or partial response (PR) at the conclusion of maintenance treatment based on RECIST 1.1 criteria. Secondary efficacy assessments include progression-free survival (PFS), the proportion of participants remaining progression-free at 2 and 3 years, and overall survival (OS). Additional parameters include the duration of response (DoR), time to subsequent therapy (TFST), and progression-free survival 2 (PFS2).
The assessment of clinical response also involves the evaluation of complete pathological response, defined by the complete disappearance of tumor in the cervix biopsy at the end of the induction phase and the maintenance treatment. The incidence of local progression and distant disease progression will be monitored. Furthermore, changes from baseline in quality of life will be evaluated using the EORTC QLQ-C30 Global Score and Physical Function subscale, the EORTC QLQ-CX24 symptom-specific scale, and the EQ-5D-5L instrument. The study will also involve the description of molecular biomarkers that may indicate clinical response, resistance, or the mechanism of action.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Has read and understand the informed consent form and has given written informed consent prior to any study procedures
- Has provided a tissue sample from a core incisional or excisional biopsy of a tumor lesion
- Subjects must have adequate hematological function: - Absolute neutrophil count (ANC) ≥1500/μL - Platelets ≥100 000/μL - Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
- Patient must have adequate renal and hepatic function: -Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/min on the basis of the Cockcroft -Gault glomerular filtration rate estimation: (140 − age) ×(weight in kg) × (0.85 if female)/72 × (serum creatinine in mg/dL); -Serum bilirubin ≤ 1.5 × ULN; with the following exception: Subjects with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled; -AST, ALT, and alkaline phosphatase < 2.5 x ULN, with the following exceptions: Patients with documented liver metastases: AST and ALT < 5 x ULN o Patients with documented liver or bone metastases: alkaline phosphatase < 5 x ULN; -Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Patients must not be pregnant or breastfeeding and agree to use highly effective contraception during the treatment period and for at least 120 days after the last dose of cemiplimab
- Participants must abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of cemiplimab or placebo and 180 days following the end of chemoradiotherapy
- Age > 18 years
- Life expectancy of at least 3 months
- Has LACC, FIGO 2018 stage IB3-IVA
- Has PD-L1 positive (PD-L1 >=1%) tumor
- Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
- Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer, including investigational agents, and is immunotherapy-naïve
- Patient must have ECOG performance status of 0 or 1
- Subjects must have measurable disease according to RECIST 1.1
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 − age) ×(weight in kg) × (0.85 if female)/72 × (serum creatinine in mg/dL)
- Serum bilirubin ≤ 1.5 × ULN; with the following exception: Subjects with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled
- AST, ALT, and alkaline phosphatase < 2.5 x ULN, with the following exceptions: Patients with documented liver metastases: AST and ALT < 5 x ULN o Patients with documented liver or bone metastases: alkaline phosphatase < 5 x ULN
- Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Exclusion Criteria
- Has histological subtypes other than those allowed per inclusion criterion 2 (eg, sarcoma, small cell carcinoma with neuroendocrine differentiation, non epithelial cancer).
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization. NOTE: Participants who have entered the Follow-up Phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
- Has any contraindication to the use of cisplatin
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). NOTE: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of HIV infection. NOTE: No testing for HIV is required unless mandated by local health authority
- Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority
- Has had an allogenic tissue/solid organ transplant.
- Has FIGO 2018 Stage IVB disease. Evidence of metastatic disease per RECIST 1.1 including lymph nodes above the L1 cephalad body or in the inguinal region. NOTE: Participants with inguinal lymph node involvement must be exscluded.
- Evidence of metastatic disease per RECIST 1.1 including lymph nodes above the L1 cephalad body, in the inguinal region. Participants with inguinal lymph node involvement should be discussed with Sponsor and may potentially be eligible after confirmation of the Sponsor with participant’s disease details
- Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy
- Has bilateral severe hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy or considered mild and not clinically significant in the opinion of the investigator
- Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
- Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and areallowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
- Has received treatment with systemic immunostimulatory agents, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-live of the drug, whichever is shorter, prior to Cycle 1, Day 1
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with anagent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
- Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization
- Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 01 Mar 2026 | 29 |
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 |
|---|---|---|---|---|---|---|
CISPLATINO SANDOZ | Other | SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 40 | 6 | PRD773633 |
LIBTAYO 350 mg concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 350 | 32 | PRD7478447 |