Neoadjuvant Tislelizumab Plus Chemo Drives Responses in Locally Advanced Cervical Cancer

Neoadjuvant treatment with tislelizumab-jsgr (Tevimbra) plus chemotherapy led to antitumor activity with a well-tolerated safety profile in patients with stage IB3 or IIA2, locally advanced cervical cancer, according to findings from the phase 2 NATIC trial (ChiCTR2200065392) published in Signal Transduction and Targeted Therapy.1

Findings showed that evaluable patients (n = 30) achieved an overall response rate (ORR) of 90.0% (95% CI, 74.4%-96.5%), including a complete response (CR) rate of 56.7% and a partial response (PR) rate of 33.3%. The remaining 10.0% of patients had a best response of stable disease. The optimal pathologic response (OPR) rate was 80.0%, where an OPR was defined as a pathologic CR (pCR; 66.7%) or a major pathologic response (MPR; 13.3%).

Regarding safety, all patients experienced any-grade treatment-related adverse effects (TRAEs), and 26.7% of patients had grade 3 TRAEs. AEs did not lead to any dose reductions, treatment discontinuation, or death.

“This combination regimen of tislelizumab plus chemotherapy has the potential to be a feasible neoadjuvant regimen for patients with locally advanced cervical cancer. The long-term survival outcomes remain pending,” Dr Jindong Sheng of the Department of Gynecological Oncology at Tianjin Medical University Cancer Institute and Hospital in China, and colleagues wrote in a publication of the data.

Why Is Immunotherapy Being Studied in the Neoadjuvant Setting for Locally Advanced Cervical Cancer?

Cisplatin-based concurrent chemoradiotherapy (CCRT) is a standard of care in the management of locally advanced cervical cancer; however, study authors noted that local recurrence and distant metastases remain a risk for a proportion of patients in this population receiving CCRT. Additionally, prior findings from the phase 3 EORTC-55994 trial (NCT00039338) showed that neoadjuvant chemotherapy alone did not improve overall survival (OS) vs CCRT alone in patients with stage IB2 to IIB cervical cancer.2

However, given the evidence for the neoadjuvant use of immunotherapy in other solid tumors, plus promising efficacy and safety outcomes from the phase 2 NACI trial (NCT04516616) evaluating neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced cervical cancer, NATIC investigators sought to examine tislelizumab plus chemotherapy in this setting.1

Notably, tislelizumab is currently approved by the FDA in combination with platinum-containing chemotherapy for the first-line treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1); as a single agent in adult patients with unresectable or metastatic ESCC after prior systemic chemotherapy that did not include a PD-L1 inhibitor; and in combination with platinum and fluoropyrimidine-based chemotherapy in adults for the first line treatment of patients with unresectable or metastatic, HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1).3

How Was Tislelizumab Evaluated in the NATIC Trial?

The investigator-initiated, single-center, single-arm, open-label NATIC trial enrolled patients 18 to 65 years of age with histologically confirmed, treatment-naive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix that was stage IB3 or IIA2 per 2018 FIGO criteria.1 Key inclusion criteria comprised an ECOG performance status of 0 or 1; adequate organ function, and at least 1 measurable lesion per RECIST 1.1 criteria.

Investigators at Tianjin Medical University Cancer Institute and Hospital excluded patients with a history of another primary malignancy within the past 5 years, those with active autoimmune disease requiring systemic treatment, and patients given systemic corticosteroids or immunosuppressive therapy within 14 days of study enrollment.

All patients received neoadjuvant tislelizumab at 200 mg on day 1 of cycles 1 to 3, paclitaxel at 175 mg/m2 on day 1 of cycles 1 to 3, and carboplatin at area under the curve 5 or cisplatin at 60 mg/m2 on day 2 of cycle 1 and day 1 of cycles 2 and 3. Patients who experienced a CR, PR, or stable disease on imaging per RECIST 1.1 criteria then underwent radical hysterectomy plus pelvic lymphadenectomy and para-aortic lymphadenectomy. Adjuvant chemotherapy, radiation, or CCRT was permitted after surgery.

The trial’s primary end point was pCR rate. Secondary end points included MPR rate, OPR rate, ORR, disease-free survival (DFS), and OS.

Investigators assessed 31 patients for eligibility, and 1 patient withdrew from the study after completing neoadjuvant therapy and refusing surgery. The 30 remaining patients all completed neoadjuvant therapy and surgery. As of the December 31, 2024, data cutoff date, 23 patients had completed all treatment and remained in study follow-up; 7 patients were still receiving adjuvant CCRT (n = 2), radiotherapy (n = 3), or chemotherapy (n = 2) and undergoing follow-up.

The 30 enrolled patients had a median age of 51.5 years (IQR, 39.5-57.0), and most patients had squamous cell carcinoma (93.3%), had FIGO 2018 stage IIA2 disease (63.3%), had an ECOG performance status of 0 (80.0%), had a PD-L1 combined positive score of at least 50 (56.7%), and were human papillomavirus virus 16 and/or 18 positive (56.7%). The median tumor size was 4.6 cm (IQR, 4.2-5.2).

What Were the Other Efficacy and Safety Outcomes for Tislelizumab/Chemotherapy?

Findings also showed that disease recurrence occurred in 2 patients, and the 18-month DFS rate was 90.0% (95% CI, 77.7%-100%). OS data remained immature, with no deaths reported across the cohort.

Additional safety data demonstrated that any-grade immune-related AEs (irAEs) were reported in 23.3% of patients, but only 1 patient (3.3%) had a grade 3 or higher irAE.

The most common any-grade TRAEs included lymphopenia (90.0%), anemia (70.0%), hypoproteinemia (70.0%), leukopenia (53.3%), neutropenia (43.3%), increased aspartate aminotransferase levels (33.3%), increased alanine aminotransferase levels (26.7%), thrombocytopenia (23.3%), rash (20.0%), pain (16.7%), nausea (16.7%), loss of appetite (16.7%), abnormal feeling (13.3%), itching (13.3%), vomit (13.3%), and lower extremity venous thrombosis (3.3%). Any-grade irAEs included hypothyroidism (16.7%), Guillain⁃Barré syndrome (3.3%), and hyperglycemia (10.0%).

References

1. Sheng J, Luo H, Liu X, et al. Tislelizumab (anti-PD-1) plus chemotherapy as neoadjuvant therapy for patients with stage IB3/IIA2 cervical cancer (NATIC): a prospective, single-arm, phase II study. Signal Transduct Target Ther. 2025;10(1):215. doi:10.1038/s41392-025-02294-9
2. Kenter GG, Greggi S, Vergote I, et al. Randomized phase III study comparing neoadjuvant chemotherapy followed by surgery versus chemoradiation in stage IB2-IIB cervical cancer: EORTC-55994. J Clin Oncol. 2023;41(32):5035-5043. doi:10.1200/JCO.22.02852
3. Tevimbra. Prescribing information. BeOne Medicines; 2025. Accessed September 15, 2025. https://beonemedicines.us/PDF/TEVIMBRAUSPI.pdf