Neoadjuvant Aitua (PD-1/CTLA-4 Bispecific) Plus Nab-Paclitaxel and Carboplatin for Advanced High-Grade Serous Ovarian Cancer

Official title

A Prospective, Randomized, Controlled Phase II Clinical Study of Albumin-Bound Paclitaxel/Carboplatin Combined With Aitua Combination Antibody (PD-1/CTLA-4 Bispecific Antibody) for the Neoadjuvant Treatment of Advanced High-Grade Serous Ovarian Cancer With Unsatisfactory Debulking

Overview

This is a prospective, randomized, controlled Phase II clinical study designed to evaluate the efficacy and safety of adding Aitua Combination Antibody (a PD-1/CTLA-4 bispecific antibody) to standard neoadjuvant chemotherapy for patients with advanced high-grade serous ovarian cancer. The study focuses on patients who are newly diagnosed with Stage IIIC-IV ovarian, fallopian tube, or primary peritoneal cancer and are assessed as unable to achieve satisfactory tumor debulking (R0 resection) initially. Participants will be randomized in a 1:1 ratio into two groups: Experimental Group: Receives Nab-paclitaxel and Carboplatin combined with Aitua Combination Antibody. Control Group: Receives Nab-paclitaxel and Carboplatin alone. Both groups will receive 3 cycles of neoadjuvant treatment followed by Interval Debulking Surgery (IDS). The primary goal is to compare the R0 resection rate (complete removal of macroscopic tumor) between the two groups during surgery. Secondary goals include assessing pathological complete response (pCR), objective response rate, progression-free survival, and safety. The study also aims to explore how this combination therapy affects the tumor immune microenvironment.

Detailed description

Background and Rationale: Ovarian cancer has the highest mortality rate among gynecological malignancies, with High-Grade Serous Carcinoma (HGSC) being the most common subtype. HGSC is characterized by a highly immunosuppressive Tumor Immune Microenvironment (TiME), often referred to as an "immune desert," which limits the efficacy of single-agent immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway.

Investigational Agent: Aitua Combination Antibody (QL1706) is a novel bifunctional antibody targeting both PD-1 and CTLA-4. Dual blockade of these pathways may synergistically activate anti-tumor immune responses: CTLA-4 inhibition promotes early T-cell activation in lymph nodes, while PD-1 inhibition reverses T-cell exhaustion within the tumor microenvironment. Previous studies in cervical cancer have shown that this bispecific antibody may offer improved efficacy with a manageable toxicity profile compared to combining two separate antibodies.

Chemotherapy Synergy: Albumin-bound paclitaxel (Nab-paclitaxel), a standard component of ovarian cancer treatment, avoids the need for corticosteroid pretreatment and has been shown to potentially enhance immune cell infiltration and regulate macrophage polarization. This study hypothesizes that combining Nab-paclitaxel/Carboplatin with the PD-1/CTLA-4 bispecific antibody will remodel the immune microenvironment and improve surgical outcomes.

Study Design: This is a single-center, open-label (with blinded assessment), randomized Phase II trial. Approximately 82 eligible patients will be stratified by FIGO stage (IIIC vs. IV) and randomized 1:1 to the experimental or control arm.

Neoadjuvant Phase: Patients receive 3 cycles of therapy (Q3W).

Surgical Phase: Patients with responsive or stable disease will undergo Interval Debulking Surgery (IDS). The primary endpoint is the R0 resection rate (no macroscopic residual disease).

Adjuvant Phase: Post-surgery, patients will continue treatment with the assigned regimen for additional cycles.

Translational Research: Tumor tissue, ascites, and peripheral blood will be collected at baseline, pre-surgery, and during therapy to analyze changes in immune cell subsets (e.g., via scRNA-seq, mIHC/mIF) and identify potential predictive biomarkers.

Interventions

• Drug Aitua Combination Antibody
  Administered via intravenous infusion at a dose of 5 mg/kg on Day 1 of each 3-week cycle.
• Drug Albumin-Bound Paclitaxel /nab-Paclitaxel
  Administered via intravenous infusion at a dose of 260 mg/m\^2 on Day 1 of each 3-week cycle.
• Drug Carboplatin (AUC 5)
  Administered via intravenous infusion at a dose of AUC 5 on Day 1 of each 3-week cycle.
• Procedure Interval Debulking Surgery
  Performed after 3 cycles of neoadjuvant therapy. The goal is to achieve R0 resection (no macroscopic residual disease).

Primary outcome measures

• Rate of R0 resection [Time frame: At the time of surgery, up to 12 weeks]

Secondary outcome measures (5)

• Pathological complete response (pCR) rate [Time frame: At the time of surgery, up to 12 weeks]
• Objective response rate (ORR) [Time frame: From baseline up to approximately 2 years]
• Disease control rate (DCR) [Time frame: From baseline up to approximately 2 years]
• Progression-free survival (PFS) [Time frame: From randomization up to approximately 2 years]
• Incidence and severity of adverse events (AEs) [Time frame: Through 28 days after the last dose of study drug, up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years.
• Histologically confirmed high-grade serous ovarian cancer (HGSC), fallopian tube cancer, or primary peritoneal cancer.
• International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Assessed by a multidisciplinary team (MDT) based on imaging (± laparoscopic exploration) as initially unable to achieve satisfactory tumor debulking (R0 resection).
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
• Major organ function is basically normal.
• Willing to provide tumor tissue, peripheral blood, and ascites samples for translational research.

Exclusion criteria

• Pathological types other than high-grade serous carcinoma (HGSC).
• Prior receipt of any form of anti-tumor therapy.
• History of autoimmune disease or requiring immunosuppressive therapy.
• Known allergy to study drug components.
• Pregnant or lactating women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07432594 · 2025-I2M-C&T-B-065

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗