AK104 and Low-dose Radiation in Recurrent/Metastatic HNSCC After Failure of First-line Systemic Therapy

NCT06494995 | Recruiting Phase 2 DMC

• 2 other identifiers: LDRT-ICB 1.02312288-4
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, there is a lack of high-quality clinical evidence for subsequent treatment options for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) after first-line treatment, especially for subsequent treatment after first-line therapy combined with PD-1 inhibitors. Increasing evidence suggests that low-dose radiation (LDRT) can reshape the tumor microenvironment.Cadonilimab is a bispecific antibody that specifically binds to CTLA-4 and PD-1 proteins in the human body. Considering that low-dose radiotherapy and cadonilimab both have immunomodulatory effects, this study intends to select recurrent metastatic HNSCC patients who have failed first-line and above treatment to explore the safety and efficacy of cadonilimab combined with low-dose radiotherapy.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

low-dose radiotherapy; low-dose radiation; cadonilimab; CTLA-4; PD-1; Stereotactic Body Radiation Therapy; Hybrid radiation; Immune modulation

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective Response Rate (ORR), as assessed by investigators according to RECIST 1.1 criteria. For patients who have received radiotherapy for all lesions, the ORR assessment should be based on the lesions that received SBRT and low-dose radiotherapy. For patients with lesions that did not receive radiotherapy, the ORR assessment should be based on the lesions that received SBRT, low-dose radiotherapy, and those that did not receive radiotherapy

  Up to two years

Secondary Outcomes (5)

• Adverse effect

  Up to two years

• Disease Control Rate

  Up to two years

• Duration of Response

  Up to two years

• Progression-free survival

  Up to two years

• Overall survival

  Up to two years

Study Arms (2)

Hybrid RT

EXPERIMENTAL

Patients will receive treatment of low-dose radiotherapy and cadonilimab, combined with selective lesions stereotactic radiotherapy.

Drug: Cadonilimab; Radiation: Low-dose radiotherapy; Radiation: SBRT

Metronomic chemotherapy and LDRT

EXPERIMENTAL

Patients will receive treatment of low-dose radiotherapy and cadonilimab, combined with capecitabine metronomic chemotherapy.

Drug: Cadonilimab; Radiation: Low-dose radiotherapy; Drug: Capecitabine

Interventions

Cadonilimab DRUG

a PD-1/CTLA-4 dual antibody

Hybrid RT; Metronomic chemotherapy and LDRT

Low-dose radiotherapy RADIATION

Low-dose radiation

Hybrid RT; Metronomic chemotherapy and LDRT

SBRT RADIATION

selected leisions to treat with stereotactic radiotherapy

Hybrid RT

Capecitabine DRUG

Capecitabine metronomic chemotherapy

Metronomic chemotherapy and LDRT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who signed the informed consent and were willing to complete the study according to the protocol;
• Aged ≥18 years and ≤75 years;
• Histologically confirmed head and neck squamous cell carcinoma or nasopharyngeal carcinoma;
• Patients with recurrent and metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma, with progression on first-line treatment or above; or locally advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma, with recurrence and metastasis within 6 months after radical radiotherapy;
• For patients with locally recurrent head and neck squamous cell carcinoma or nasopharyngeal carcinoma, those who are not suitable for local treatment after multidisciplinary evaluation of head and neck tumors;
• At least one measurable lesion before treatment, that is, meeting the "measurable lesion" requirement in the RECIST 1.1 standard;
• Expected survival period\>3 months;
• ECOG score 0-2 points;
• Good organ function: meet the following requirements:
• Absolute neutrophil count (ANC) ≥1.5×109/L;
• Platelet count ≥100×109/L;
• Hemoglobin ≥9g/dL;
• Serum albumin ≥2.8g/dL;
• Total bilirubin ≤1.5×ULN, ALT, AST and/or ALP ≤3×ULN;
• Serum creatinine ≤1.5×ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault, see Appendix 3);

You may not qualify if:

• Patients who have received anti-CTLA-4 antibodies, or any other antibodies or drugs targeting T cell co-stimulation or checkpoint pathways, or small molecule tyrosine kinase inhibitors, including lenvatinib, anlotinib, apatinib, etc.;
• Patients with symptoms of spinal cord compression, risk of pathological fracture, or emergency surgery and/or radiotherapy due to other medical needs;
• Patients with a history of gastrointestinal perforation and/or fistula within 6 months before enrollment (if the gastrointestinal perforation or fistula has been surgically removed, enrollment is allowed);
• Patients with necrotic lesions within 4 weeks before enrollment, or tumors directly invading the trachea, bronchus, esophagus, or arteries, and who are judged by the investigator to have a risk of major bleeding;
• Patients with other malignant tumors in the past or at the same time (except for malignant tumors that have been cured and have survived without cancer for more than 3 years, such as basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma);
• Uncontrolled clinical symptoms or diseases of the heart, such as: a. NYHA heart failure of grade II or above; b. Unstable angina pectoris; c. Myocardial infarction within 1 year; d. Patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
• Received any of the following treatments:
• Received any research drug within 4 weeks before the first use of the study drug;
• Enrolled in another clinical study at the same time, unless it is an observational (non-interventional) clinical study;
• Subjects who need to be given corticosteroids (daily prednisone equivalent dose of \>10 mg) or other immunosuppressants for systemic treatment within 2 weeks before the first use of the study drug, except for the use of corticosteroids for local inflammation and prevention of allergies, nausea and vomiting. Other special cases need to be communicated with the investigator. In the absence of active autoimmune diseases, inhaled or topical steroids and adrenocortical hormone replacement at a dose of \>10 mg/day prednisone are allowed;
• Patients who have received anti-tumor vaccines or have received vaccines (including live vaccines or inactivated vaccines) within 4 weeks before the first administration of the study drug;
• Patients who have undergone major surgery or severe trauma within 4 weeks before the first use of the study drug;
• Severe infection (CTCAE\>2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, infectious complications, etc. requiring hospitalization; baseline chest imaging examinations indicate active lung inflammation, symptoms and signs of infection within 4 weeks of the first use of the study drug, or the need for oral or intravenous antibiotic treatment;
• Active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); but not including autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; type 1 diabetes using stable doses of insulin; patients with vitiligo or healed childhood asthma/allergies who do not require any intervention as adults;
• Patients with a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation and allogeneic bone marrow transplantation;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (3)

• Keam SJ. Cadonilimab: First Approval. Drugs. 2022 Aug;82(12):1333-1339. doi: 10.1007/s40265-022-01761-9.

  PMID: 35986837 BACKGROUND

• Gao X, Xu N, Li Z, Shen L, Ji K, Zheng Z, Liu D, Lou H, Bai L, Liu T, Li Y, Li Y, Fan Q, Feng M, Zhong H, Huang Y, Lou G, Wang J, Lin X, Chen Y, An R, Li C, Zhou Q, Huang X, Guo Z, Wang S, Li G, Fei J, Zhu L, Zhu H, Li X, Li F, Liao S, Min Q, Tang L, Shan F, Gong J, Gao Y, Zhou J, Lu Z, Li X, Li J, Ren H, Liu X, Yang H, Li W, Song W, Wang ZM, Li B, Xia M, Wu X, Ji J. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Lancet Oncol. 2023 Oct;24(10):1134-1146. doi: 10.1016/S1470-2045(23)00411-4.

  PMID: 37797632 BACKGROUND

• Herrera FG, Ronet C, Ochoa de Olza M, Barras D, Crespo I, Andreatta M, Corria-Osorio J, Spill A, Benedetti F, Genolet R, Orcurto A, Imbimbo M, Ghisoni E, Navarro Rodrigo B, Berthold DR, Sarivalasis A, Zaman K, Duran R, Dromain C, Prior J, Schaefer N, Bourhis J, Dimopoulou G, Tsourti Z, Messemaker M, Smith T, Warren SE, Foukas P, Rusakiewicz S, Pittet MJ, Zimmermann S, Sempoux C, Dafni U, Harari A, Kandalaft LE, Carmona SJ, Dangaj Laniti D, Irving M, Coukos G. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discov. 2022 Jan;12(1):108-133. doi: 10.1158/2159-8290.CD-21-0003. Epub 2021 Sep 3.

  PMID: 34479871 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Radiotherapy; Capecitabine

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Yu Wang, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaomin Ou, M.D.

CONTACT

+8621-64175590; 0456218@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, M.D.

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 10, 2024
• Study Start: July 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)