IN10018 With Nab-Paclitaxel and Cadonilimab for Metastatic or Recurrent Gastric-Type Cervical Adenocarcinoma: Phase 2 Trial

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

Gastric-type adenocarcinoma of the cervix is the most commonly diagnosed HPV-independent subtype of cervical cancer, characterized by a poor prognosis and limited responsiveness to existing therapies. Therefore, the exploration of new treatment modalities is critically important. This is an open-label, single-arm, multi-center clinical trial to evaluate the efficacy and safety of IN10018 plus nab-paclitaxel and cadonilimab in the treatment of adult women with metastatic, recurrent, or persistent gastric-type adenocarcinoma of the cervix.

Study Overview

• Status: Recruiting
• Conditions: Cervical Adenocarcinoma; Gastric-type Endocervical Adenocarcinoma
• Intervention / Treatment: Drug: IN10018; Drug: Nab-paclitaxel; Drug: Cadonilimab

Detailed Description

Subjects will receive IN10018 at a dose of 100 mg orally once daily, in combination with nab-paclitaxel at 260 mg/m² and cadonilimab at 10 mg/kg, both administered via intravenous infusion on Day 1 of each 3-week cycle. Tumor assessments will be conducted every 2 cycles throughout the treatment period. If the therapy proves effective, chemotherapy will continue for up to 6 cycles. Upon completion of chemotherapy, maintenance therapy with cadonilimab and IN10018 will begin and continue until either disease progression or the emergence of intolerable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Wu, Ph.D; Phone Number: +86 13995573729; Email: pengwu8626@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Peng Wu, Ph.D; Phone Number: +86 13995573729; Email: pengwu8626@tjh.tjmu.edu.cn
    • Xiangyang, Hubei, China, 441000
      • Recruiting
      • Xiangyang Central Hospital
      • Contact: Xiaomin Qin; Phone Number: +86 13487120205; Email: 13487120205@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study group; IN10018 is administered orally at a dose of 100 mg once daily; cadonilimab is given at a dose of 10 mg/kg via intravenous infusion on Day 1 of each cycle, every 3 weeks; and nab-paclitaxel is administered at a dose of 260 mg/m² via intravenous infusion on Day 1 of each cycle, also every 3 weeks. Patients will undergo a maximum of 6 cycles of this combination chemotherapy. Following this regimen, maintenance therapy will consist of a combination of cadonilimab and IN10018.

Drug: IN10018; 100 mg, orally, once daily; Other Names: BI 853520; Drug: Nab-paclitaxel; 260 mg/m², IV infusion, Q3W; Other Names: Albumin-bound paclitaxel; Drug: Cadonilimab; 10 mg/kg, IV infusion, Q3W; Other Names: AK104

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of the participants in the ITT population who have a complete response (CR) or partial response (PR). The ORR will be assessed by a blind independent central reviewer per RECIST 1.1	Every 6 weeks from the time of the first dose of the study drug until the completion of treatment, lasting approximately 18 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the time from the first dose of study treatment/randomization to the first documentation of disease progression or death due to any cause, whichever comes first	2 years
Disease Control Rate (DCR)	DCR is defined as the proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) following treatment. The DCR will be assessed by a blind independent central reviewer per RECIST 1.1	Every 6 weeks from the time of the first dose of the study drug until the completion of treatment, lasting approximately 18 weeks.

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Investigators: Principal Investigator: Peng Wu, Ph.D, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 20, 2024
• First Submitted That Met QC Criteria: October 21, 2024
• First Posted (Actual): October 23, 2024

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 11, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Albumins; Paclitaxel; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: UHCT240895

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Ethical and legal considerations necessitate the protection of participants' privacy, particularly when dealing with sensitive data that may identify individuals. Additionally, if data analyses remain incomplete, disclosing individual participant data (IPD) could compromise the integrity of the results and lead to hasty conclusions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No