AzTrials
AzTrials

Head and Neck Squamous Cell CarcinomaPhase 2NCT06494995

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

A Phase 2 study testing Cadonilimab, Low-dose radiotherapy and SBRT in people with Head and Neck Squamous Cell Carcinoma, run by Fudan University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Cadonilimab, Low-dose radiotherapy and SBRT
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
1 siteChina
Study dates
3 Jul 2024to 1 Jul 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 19Show fewer
  • 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);
  • Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5× ULN (screening is allowed for patients who are taking stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin and whose INR is within the expected therapeutic range of the anticoagulant);
  • Patients with hepatitis B virus (HBV) infection and inactive/asymptomatic HBV carriers, or patients with chronic or active HBV, will be allowed to enroll if HBV DNA <500 IU/mL (or 2500 copies/mL) at screening. Patients with positive hepatitis C antibodies will be allowed to enroll if HCV-RNA is negative at screening.
  • Women of childbearing age need to have a negative urine or serum pregnancy test result within ≤7 days before treatment. And use a medically approved contraceptive method (such as intrauterine device, birth control pills or condoms) during the study treatment, at least 3 months after the last use of cadonilimab, and at least 6 months after the last use of chemotherapy;
  • Male subjects who are not sterilized must be willing to use a medically approved contraceptive method (such as intrauterine device, birth control pills or condoms) during the study treatment, at least 3 months after the last use of cadonilimab, and at least 6 months after the last use of chemotherapy.

Who cannot join

  • 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;
Show all 22Show fewer
  • 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;
  • The toxicity of previous anti-tumor treatment has not recovered to ≤CTCAE grade 1 (except for sequelae of alopecia and neurotoxicity related to previous platinum treatment) or the level specified by the inclusion/exclusion criteria;
  • 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;
  • Patients with a history of interstitial lung disease (excluding radiation pneumonia without steroid treatment) or non-infectious pneumonia;
  • Patients with active pulmonary tuberculosis infection found through medical history or CT examination, or patients with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or patients with a history of active pulmonary tuberculosis infection more than 1 year ago but without formal treatment;
  • Subjects with active hepatitis B (HBV DNA ≥500 IU/mL or 2500 copies/mL), hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the detection limit of the analytical method);
  • known history of psychotropic drug abuse, alcoholism or drug abuse;
  • pregnant or lactating women;
  • the researcher judges that the subject has other factors that may force him to terminate the study midway, such as other serious diseases (including mental illness) requiring combined treatment, serious abnormal laboratory test values, family or social factors that may affect the safety of the subject or the collection of trial data.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Xiaomin Ou, M.D. contact

+8621-64175590 ext. 67148

0456218@fudan.edu.cn

China1 site, 1 recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200032

    Yu Wang, M.D., +8618017313971, neck130@hotmail.com

    Xiaomin Ou, M.D., +8618017317872, 0456218@fudan.edu.cn

    Recruiting

Other trials in China

About this study

Official title: The Combination of AK104 and Low-dose Radiation Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma After Failure of First-line Systemic Therapy: a Phase II Study

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.

Read the detailed description

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, polarize macrophages towards M1, and M1 macrophages secrete chemokines to promote the recruitment of effector T cells while inducing vascular normalization.

Cadonilimab is a bispecific antibody that specifically binds to CTLA-4 and PD-1 proteins in the human body. It is the first approved PD-1/CTLA-4 bispecific antibody. In June 2022, cadonilimab was approved by the NMPA for the treatment of recurrent or metastatic cervical cancer patients after platinum-based chemotherapy failure. The drug is currently undergoing clinical trials for other types of cancers, including non-small cell lung cancer, hepatocellular carcinoma, gastric cancer, esophageal cancer, and nasopharyngeal cancer.

In view of the subsequent treatment strategies for recurrent metastatic HNSCC after first-line treatment progress, there is still a lack of high-level evidence-based medical evidence to confirm the best recommendation for subsequent treatment. 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.

Being tested
Cadonilimab, Low-dose radiotherapy, SBRT, Capecitabine
Keywords
low-dose radiotherapy, low-dose radiation, cadonilimab, CTLA-4, PD-1, Stereotactic Body Radiation Therapy, Hybrid radiation, Immune modulation
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CadonilimabDrug

    a PD-1/CTLA-4 dual antibody

  • Low-dose radiotherapyRadiation

    Low-dose radiation

  • SBRTRadiation

    selected leisions to treat with stereotactic radiotherapy

  • CapecitabineDrug

    Capecitabine metronomic chemotherapy

Study groups in NCT06494995
Study groupRoleWhat they receive
Hybrid RTExperimentalPatients will receive treatment of low-dose radiotherapy and cadonilimab, combined with selective lesions stereotactic radiotherapy.
Receives: Drug: Cadonilimab; Radiation: Low-dose radiotherapy; Radiation: SBRT
Metronomic chemotherapy and LDRTExperimentalPatients will receive treatment of low-dose radiotherapy and cadonilimab, combined with capecitabine metronomic chemotherapy.
Receives: Drug: Cadonilimab; Radiation: Low-dose radiotherapy; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to two years

Secondary outcomes (5)

  1. Adverse effect

    Adverse effects (AE) as evaluated by CTCAE 5.0

    Measured: Up to two years

  2. Disease Control Rate

    Disease Control Rate (DCR), as assessed by investigators according to RECIST 1.1 criteria

    Measured: Up to two years

  3. Duration of Response

    Duration of Response (DoR), as assessed by investigators according to RECIST 1.1 criteria

    Measured: Up to two years

  4. Progression-free survival

    Progression-free survival (PFS): from the start of enrollment to the first recorded date of objective tumor progression or death from any cause, whichever occurs first.

    Measured: Up to two years

  5. Overall survival

    Overall survival (OS): the time from enrollment to death due to any cause.

    Measured: Up to two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2024
  2. Study start3 Jul 2024
  3. Primary completion1 Jul 2026 (estimated)
  4. Study completion1 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06494995
Sponsor's protocol ID
LDRT-ICB 1.0
Other IDs
2312288-4
Status last verified
May 2025
First submitted
3 Jul 2024
Last updated
4 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No plan to share IPD unless special request to principal invesitgators with formal applications.

Publications

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

    PubMed 35986837

  • 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.

    PubMed 37797632

  • 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.

    PubMed 34479871

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cadonilimab, Low-dose radiotherapy and SBRT in people with Head and Neck Squamous Cell Carcinoma, run by Fudan University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xiaomin Ou, M.D. (+8621-64175590 ext. 67148, 0456218@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: Up to two years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06494995, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in