Neoadjuvant Checkpoint Blockade Shows Efficacy, Safety in Cervical Cancer

The GINECO window-of-opportunity COLIBRI (NCT04256213) study provides compelling evidence that a neoadjuvant "priming" dose of dual immune checkpoint blockade (ICB) before standard chemoradiation is a feasible, tolerable, and highly effective strategy for treating patients with locally advanced cervical cancer.^1,2

The phase 2 trial demonstrated that 1 cycle of nivolumab (Opdivo) plus ipilimumab (Yervoy) significantly remodels the tumor immune microenvironment, converting immunologically "cold" tumors to "hot" and measurably increasing the presence of cancer-fighting T-cells.

This immune modulation translated into exceptional clinical outcomes. While the initial response to immunotherapy alone was modest (13% objective response rate [ORR]), the rates after subsequent chemoradiation were remarkably high, culminating in a 90% ORR, including a 78% complete response rate, at the end of treatment.

The study successfully met its primary end point, demonstrating significant immune activation after 1 cycle of nivolumab and ipilimumab.

There was a statistically significant increase in the ratio of effector CD8+ T cells to regulatory FOXP3+ T cells, with a mean increase of 0.87 cells/mm² (P =.0164).

The immunotherapy triggered a drastic increase in the density of proliferative (Ki67+) CD4+ and CD8+ T cells (both P <.0001).

Densities of both CD4+ T effector cells (P =.0091) and CD8+ T effector cells (P =.0132) significantly increased in the tumor.

The HTG HOT score, a 27-gene signature identifying immunologically active tumors, increased significantly (P <.0001). The proportion of patients with "hot" tumors rose from 26% (n = 10/39) at baseline to 56% (n = 22/39) after immunotherapy.

The neoadjuvant immunotherapy approach followed by standard care resulted in deep and durable clinical responses. By the data cutoff date of February 11, 2023, with a median follow-up of 95 weeks, only 6 patients (15%) had experienced disease progression.

Safety and Tolerability

The regimen was well-tolerated with no new safety signals. No treatment-related deaths occurred.

In the neoadjuvant phase, grade ≥ 3 treatment-related adverse events (TRAEs) occurred in only 1 patient (3%), which was a case of grade 3 asthenia. The most common any-grade TRAEs were asthenia (28%) and pruritus (20%).

In the chemoradiation phase, grade ≥ 3 TRAEs occurred in 11 patients (28%). The most common any-grade AEs were diarrhea (58%), nausea (53%), and anemia (48%).

In the maintenance phase, grade ≥3 TRAEs occurred in 7 patients (18%). Asthenia (26%) was the most common any-grade AE.

“The COLIBRI trial in [locally advanced cervical cancer] demonstrates the feasibility and tolerability of dual nivolumab plus ipilimumab ICB before chemoradiation followed by up to 6 months of maintenance nivolumab after chemoradiation,” stated Ray-Coquard et al, authors of the study.

Study Rationale

Cisplatin-based chemoradiation is the standard of care for locally advanced cervical cancer, but it is insufficient for a significant portion of patients, with up to 30% experiencing recurrence within 2 years. This represents a major area of unmet clinical need. While combining ICB with chemotherapy has shown survival benefits in recurrent or metastatic cervical cancer, its optimal integration into the locally advanced cervical cancer setting is still being defined.

The COLIBRI trial was designed to test the "window-of-opportunity" concept, where neoadjuvant immunotherapy is administered before local therapy (chemoradiation). The rationale is that the presence of the in-situ tumor provides a rich source of antigens, allowing the ICB to potently reinvigorate and expand tumor-specific T-cell clones. The study specifically investigated the dual blockade of PD-1 (nivolumab) and CTLA-4 (ipilimumab), as their co-expression is associated with severe T-cell dysfunction. The primary objective was to determine if this approach could favorably modulate the tumor immune microenvironment before the start of standard treatment.

Study Design and Patient Population

The COLIBRI trial was a multicenter, single-arm, phase 2 pilot study that enrolled 40 patients in France between June 2020 and August 2021. The median age of patients was 55 years (range, 31-77).

A single cycle of intravenous ipilimumab (1 mg/kg) was administered on day 1 and nivolumab (3 mg/kg) on days 1 and 15. Standard chemoradiation was administered 5 to 8 weeks after the start of the neoadjuvant phase. Following chemoradiation, patients received maintenance nivolumab (480 mg every 4 weeks) for 6 months. Mandatory tumor biopsies were collected at baseline (before ICB) and after the neoadjuvant phase (before chemoradiation).

While the study is limited by its small sample size and single-arm design, its robust translational findings provide a clear path forward. The results support further evaluation of neoadjuvant sequencing strategies for high-risk locally advanced cervical cancer. This is currently being explored in the randomized phase 2 COLIBRI-2 trial (NCT06715241),³ which is investigating nivolumab with or without the LAG3 inhibitor relatlimab (Opdualag) as induction therapy before standard chemoradiation.

REFERENCES

1.Ray-Coquard I, Kaminsky-Forrett M, Ohkuma R, et al. Neoadjuvant immune checkpoint blockade before chemoradiation for cervical squamous carcinoma (GINECO window-of-opportunity COLIBRI study): a phase II trial. Published January 5, 2026. Accessed January 28, 2026. Nat Commun 17, 922 (2026). doi: 10.1038/s41467-025-67646-z.

2.COL immunotherapy before radiochimio + ipilimumab (COLIBRI). ClinicalTrials.gov. Updated December 12, 2024. Accessed January 28, 2026. https://clinicaltrials.gov/study/NCT04256213

3.A multicenter, seeking signal, randomised, open-label phase II of relatlimab and nivolumab vs nivolumab alone in locally advanced cervical cancers (COLIBRI-2). ClinicalTrials.gov. Updated January 22, 2026. Accessed January 28, 2026. https://clinicaltrials.gov/study/NCT06715241