IN10018 plus nab-paclitaxel and cadonilimab for metastatic or recurrent gastric-type cervical adenocarcinoma.

IN10018 Plus Nab-Paclitaxel and Cadonilimab for Metastatic, Recurrent, or Persistent Gastric-Type Adenocarcinoma of the Cervix: A Multicenter, Single-Arm, Phase II Trial

This trial will test whether combining IN10018 with nab-paclitaxel and cadonilimab helps adult women whose gastric-type cervical adenocarcinoma has come back or spread after prior chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: cadonilimab, immunotherapy, radiation, prednisone, chemotherapy
• Locations: 2 sites (Wuhan, Hubei and 1 other locations)
• Trial ID: NCT06654011 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm, multi-center Phase 2 trial enrolling adult women with metastatic, recurrent, or persistent gastric-type endocervical adenocarcinoma not amenable to curative therapy. Participants receive oral IN10018 100 mg once daily with intravenous nab-paclitaxel 260 mg/m² and cadonilimab 10 mg/kg on Day 1 of each 3-week cycle, with tumor imaging every two cycles. Chemotherapy may continue for up to six cycles; after chemotherapy, maintenance therapy with cadonilimab plus IN10018 continues until disease progression or intolerable toxicity. Eligible patients must have measurable disease, ECOG performance status 0–1, and at least one prior systemic chemotherapy regimen for metastatic/recurrent disease.

Who should consider this trial

Good fit: Adult women (18–75 years) with metastatic, recurrent, or persistent gastric-type cervical adenocarcinoma not curable by surgery or radiation, who have measurable disease, ECOG 0–1, and at least one prior systemic chemotherapy for their metastatic or recurrent cancer.

Not a fit: Patients without gastric-type histology, those with ECOG performance status >1, those lacking measurable disease, or those still eligible for curative local therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could shrink tumors, slow disease progression, and extend time without worsening of disease for women with this hard-to-treat subtype.

How similar studies have performed: Immune checkpoint inhibitors plus chemotherapy have shown benefit in some cervical cancers, but combinations specifically targeting HPV-independent gastric-type endocervical adenocarcinoma are largely untested and represent a relatively novel approach.

Eligibility criteria

Inclusion Criteria:

1. Females 18-75 years of age.
2. Patients must have metastatic, recurrent or persistent gastric-type adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
3. Patients must have had at least one prior systemic chemotherapeutic regimen for metastatic, recurrent or persistent carcinoma of the cervix. (Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of metastatic, recurrent or persistent carcinoma of the cervix, adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT).
4. Patients must have measurable disease per REClST 1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis.
5. Eastern Cooperative Oncology Group score 0-1.
6. Life expectancy exceeds 3 months.
7. AEs due to previous treatments should be resolved to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy are eligible.
8. NEU ≥ 1.5\*10\^9 /L, Platelet ≥ 75×10\^9 /L, Hemoglobin ≥ 90 g/L; Serum creatinine ≤ 1.5 times the upper limit of normal (ULN).; Urinary protein \< 2+ or 24h urinary protein quantity \< 1.0 g; AST and ALT ≤ 2.5 times ULN; Total bilirubin ≤ 1.5 times ULN; Albumin levels ≥ 28 g/L; Coagulation function: Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 times the ULN.
9. Female participants must test negative for HCG in urine or blood, except in cases of menopause or prior hysterectomy. Female patients of childbearing potential and their partners must use effective contraception during the study and for 6 months after the final dose of the study drug.
10. Willing to participate in this study, and sign the informed consent.

Exclusion Criteria:

1. Patients with cervical cancer histologically diagnosed as squamous cell carcinoma, usual-type adenocarcinoma, clear cell carcinoma, adenosquamous carcinoma, small cell carcinoma, or any non-gastric-type adenocarcinoma.
2. Participate in other drug clinical trials at the same time.
3. Known hypersensitivity to any component of the IN10018 formulation or to cadonilimab.
4. Patients with active autoimmune disease or a history of autoimmune disorders.
5. Patients with concomitant conditions requiring immunosuppressive medications or systemic or absorbable local corticosteroids at immunosuppressive doses. The use of prednisone \>10 mg/day or an equivalent dose is prohibited within 2 weeks prior to the first administration of the investigational drug.
6. HIV infection or a positive test for acquired immunodeficiency syndrome (AIDS).
7. Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
8. Necrotic lesions identified within 4 weeks prior to enrollment, where there is a high risk of major bleeding as determined by the investigator.
9. Severe infections occurring within 4 weeks prior to the first dose of study treatment.
10. Known active tuberculosis (TB) or suspicion of active TB.
11. Untreated chronic hepatitis B infection or hepatitis B virus (HBV) carriers with HBV DNA levels exceeding 1000 IU/mL, or patients with active hepatitis C infection.
12. Patients with known leptomeningeal disease, spinal cord compression, or active brain metastases.
13. Uncontrolled severe medical conditions that, in the investigator's judgment, would interfere with the patient's ability to receive study treatment, including but not limited to severe cardiovascular disease, cerebrovascular disease, uncontrolled diabetes, or uncontrolled infections.
14. Receipt of a live vaccine within 4 weeks prior to the first dose of study treatment. Note: Inactivated seasonal influenza vaccines are permitted.
15. Pregnant or breastfeeding female patients, or female patients of childbearing potential who refuse to use effective contraception.
16. Patients with symptomatic or unstable third-space fluid accumulations (e.g., pleural effusion, ascites, pericardial effusion) requiring repeated drainage.
17. Patients with a prior genetic test report indicating mutations associated with hyperprogression under immunotherapy, such as MDM2/4 amplification or EGFR mutations.
18. Not eligible for the study judged by researchers.

Where this trial is running

Wuhan, Hubei and 1 other locations

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Xiangyang Central Hospital — Xiangyang, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Peng Wu, Ph.D — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
• Study coordinator: Peng Wu, Ph.D

Conditions Cervical Adenocarcinoma; Gastric-type Endocervical Adenocarcinoma