We aim to determine feasibility, safety and efficacy of TDLN-targeted immune checkpoint inhibition in different doses (nivolumab) in patients with cervical cancer.
Female participants with uterus and cervix in situ who are at least 18 years of age on the day of signing informed consent with histologically confirmed primary diagnosis of cervical cancer and are intended to be treated with standard-of-care surgery (< FIGO IB3). Only female participants with reproductive organs still in situ are eligible because this ensures the highest chance of the correct lymph(node) anatomy needed for the administration of the IMP;
The participant is not pregnant, not breastfeeding, is not a woman of childbearing potential (WOCBP) or agrees to follow contraceptive guidance as described in 9.2.1. during the treatment period and at least until SoC surgery;
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Single group
Nivolumab
DrugSubcutaneous injection of nivolumab
Feasibility: Proportion of participants undergoing planned standard surgical treatment after 2 cycles of TDLN-targeted neoadjuvant ICI without treatment-related delay or cancellation.
Feasibility will be assessed as the proportion of participants who complete 2 cycles of neoadjuvant TDLN-targeted immune checkpoint inhibition and subsequently undergo planned standard surgical treatment without treatment-related delay or cancellation.
Pathologic response rate
At least one partial pathologic response (pPR) must be observed, irrespective of dose level. All further pathologic responses will be reported on using descriptive statistics for the estimated percentage of viable remaining cancer cells at the end of the study period and defined based on work in other cancers such as melanoma, breast and colorectal cancer with: * pPR - \<90% vital tumor cells * pNCR - \<10% vital tumor cells in the tumor * pCR - the complete absence of viable cancer cells in the tumor
Safety and toxicity
Adverse events be monitored in the current trial using GCP guidelines. All AEs will be followed until they have abated, or until a stable situation has been reached. The reporting period for all AEs begins with signing the ICF. Patients will visit the hospital in weeks 12, 21 and 33 to monitor potential long-term effects of the nivolumab.
Radiologic responses
MRI will be performed at baseline (SoC diagnostic workup) and will be compared to MRI performed prior to surgery (week 11). Tumor response will be classified according to RECIST 1.1: * Complete Response (CR): Disappearance of all target lesions. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. * Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest-sum-on-study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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