Nasopharyngeal Cancinoma (NPC)Phase 3NCT06664983
TPC Combined With Cadonilimab VS. TPC Alone in Anti-PD-1 Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma
A Phase 3 study testing TPC chemotherapy and cadonilimab combined TPC chemotherapy in people with Nasopharyngeal Cancinoma (NPC), run by Sun Yat-sen University at 1 site in China.
Trial summary
With the advancement of large-scale phase III clinical studies such as RATIONALE-309, JUPITER-02, and CAPTAIN-1, the GP regimen combined with immunotherapy has become the recommended first-line treatment for recurrent metastatic nasopharyngeal carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nasopharyngeal Cancinoma (NPC)
- What is being tested?
- TPC chemotherapy and cadonilimab combined TPC chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteChina
- Study dates
- 21 Oct 2024to 21 Oct 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.Histopathological diagnosis confirmed as non-keratinizing nasopharyngeal carcinoma.
- 2.Confirmed diagnosis of metastatic or recurrent nasopharyngeal carcinoma, not suitable for radical local treatment.
- 3.Patients who have failed first-line or subsequent anti-PD-1 antibody immunotherapy (either monotherapy or combination therapy).
- 4.Age between 18 and 70 years. 5.Generally good condition, ECOG score of 0-1, with a life expectancy of ≥3 months.
- 6.At least one measurable lesion (according to RECIST 1.1); lesions that have been previously irradiated can be considered target lesions if imaging diagnosis clearly shows progression and they are measurable.
- 7.Adequate organ and bone marrow function, specifically hemoglobin (HGB) ≥ 80 g/L, white blood cells (WBC) ≥ 4×10^9/L, and platelets (PLT) ≥ 75×10^9/L. Liver function: total bilirubin (TBIL) < 1.5 times the upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 2.5 times the ULN; serum albumin (ALB) ≥ 28 g/L; if the patient has liver metastases, ALT or AST < 5×ULN; if the patient has liver or bone metastases, alkaline phosphatase (AKP) < 5×ULN. Prothrombin time (PT) international normalized ratio/PTT < 1.5 times the ULN; cardiac function requirement is left ventricular ejection fraction (LVEF) ≥ 50%.
- 7.Voluntarily participate and sign the informed consent form, and accept and comply with the study protocol, laboratory tests, follow-ups, etc.
- 8.Female subjects of childbearing potential and male subjects with fertile partners must agree to use effective contraception (such as condoms, regularly prescribed contraceptive pills, etc.) from screening until 6 months after the last treatment.
Who cannot join
- 1.History of hypersensitivity to monoclonal antibodies. 2.Time interval of less than 6 months from the last first-line TPC chemotherapy.
- 3.Known history of interstitial pneumonia. 4.Severe infection occurring within 4 weeks prior to the first administration, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
- 5.Patients who have used aspirin (>325 mg/day) or dipyridamole, ticlopidine, clopidogrel, and cilostazol within 3 weeks prior to medication, or anticoagulants requiring INR monitoring (such as warfarin), or those who have received any blood components and cell growth factor support therapy within 1 week prior to medication.
- 6.Active infections requiring systemic treatment. 7.Active hepatitis B (HBV-DNA ≥ 1000 IU/ml) that persists despite treatment, excluding those with cured hepatitis C; significant clinical bleeding symptoms or a clear bleeding tendency within 1 month prior to medication.
- 8.Received the last radiotherapy or antitumor treatment within 3 weeks prior to the first administration.
- 9.Known history of active tuberculosis or autoimmune diseases. 10.Patients with HIV infection. 11.Presence of other uncontrolled malignancies. 12.Abnormal function of major organs such as the heart, brain, or lungs, or clinical significance of hydronephrosis, ascites, pericardial effusion, or those undergoing thrombolytic therapy.
- 13.Pregnant or breastfeeding women. 14.Individuals with personality or mental disorders, or those lacking full civil capacity or having limited civil capacity.
- 15.Currently participating in an interventional clinical study treatment, or having received treatment with other investigational drugs within 4 weeks prior to the first administration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase III Clinical Study Comparing the Combination of TPC Regimen With Cadonilimab Against the TPC Regimen Alone in Anti-PD-1 Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma
With the advancement of large-scale phase III clinical studies such as RATIONALE-309, JUPITER-02, and CAPTAIN-1, the GP regimen combined with immunotherapy has become the recommended first-line treatment for recurrent metastatic nasopharyngeal carcinoma. However, patients receiving first-line chemotherapy plus immunotherapy have a median progression-free survival time of only 9.6 to 21.4 months, indicating that disease progression is still inevitable after first-line chemo-immunotherapy in patients with recurrent/metastatic nasopharyngeal carcinoma. Therefore, second or subsequent line treatment options are crucial for the management of patients with recurrent/metastatic nasopharyngeal carcinoma.
In 2021, the International Society for Cancer Immunotherapy reported a multicenter, open-label, single-arm phase II clinical study of cadonilimab in patients with metastatic nasopharyngeal carcinoma who had failed second-line or subsequent chemotherapy. The data showed that among the 20 evaluable patients enrolled, the objective response rate for cadonilimab monotherapy reached 30%, with a disease control rate of 70%, and the median progression-free survival time was 3.71 months. These study results suggest that cadonilimab demonstrates encouraging anti-tumor activity and good safety in patients with metastatic nasopharyngeal carcinoma who have failed second-line or subsequent chemotherapy.
Read the detailed description
Cadonilimab (AK104) is humanized bispecific antibody that targets to PD-1 and CTLA-4 . Its tetravalent and no Fc binding design contribute to its high binding activity in the tumor microenvironment and improved safety profile . Recent studies have shown encouraging efficacy and manageable toxicity of cadonilimab in several different cancer types. Cadonilimab monotherapy has shown an ORR of 30% and disease control rate (DCR) of 70%, with the median disease-free survival time of 3.71 months in patients with RM-NPC at the second line setting. There is no study available to explore the role of cadonilimab in anti-PD-1 resistant RM NPC patients.
Our previous study prospectively proven the superiority of TPC regimen (paclitaxel, cisplatin, and capecitabine) versus cisplatin and fluorouracil (PF) as induction treatment for patients with stage IVA NPC in NPC patients. Besides, after achieved disease control from TPC regimen induce therapy, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC with tolerate toxic . These results suggest the promising application prospect of TPC regimen in RM-NPC patients.
- Conditions
- Nasopharyngeal Cancinoma (NPC)
- Being tested
- TPC chemotherapy, cadonilimab combined TPC chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPC chemotherapyDrug
Also called NAB-paclitaxel, cisplatin, and capecitabine
The TPC regimen included NAB-paclitaxel administered at a dose of 200 mg/m2 on day 1, cisplatin at a dose of 60 mg/m2 on day 1, and capecitabine at a dose of 1000 mg/m2, taken orally twice a day on days 1 to 14, for each cycle
cadonilimab combined TPC chemotherapyDrug
Also called cadonilimab combined NAB-paclitaxel, cisplatin, and capecitabine
Cadonilimab was intravenously given at dose of 10 mg/kg on day 1. The TPC regimen included NAB-paclitaxel administered at a dose of 200 mg/m2 on day 1, cisplatin at a dose of 60 mg/m2 on day 1, and capecitabine at a dose of 1000 mg/m2, taken orally twice a day on days 1 to 14, for each cycle
| Study group | Role | What they receive |
|---|---|---|
| TPC chemotherapy | Active comparator | NAB-paclitaxel; cisplatin or lobaplatin and capecitabine Receives: Drug: TPC chemotherapy |
| Cadonilimab with TPC chemotherapy | Experimental | cadonilimab plus TPC chemotherapy (NAB-paclitaxel, cisplatin or lobaplatin ; and capecitabine Receives: Drug: cadonilimab combined TPC chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
The primary endpoint was PFS, which was assessed as the time from randomization to disease progression per RECIST v1.1 assessed by IRC or death, whichever occurred first.
Measured: from the enrollment to disease progression or death from any cause, assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2024
- Study start21 Oct 2024
- Primary completion21 Oct 2025 (estimated)
- Study completion21 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal Cancinoma (NPC)Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, XIANG YANQUN, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06664983
- Sponsor's protocol ID
- B2024-581-02
- Status last verified
- Oct 2024
- First submitted
- 17 Oct 2024
- Last updated
- 30 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III Clinical Study Comparing the Combination of TPC Regimen With Cadonilimab Against the TPC Regimen Alone in Anti-PD-1 Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT06664983
- Acronym / sponsor ID
- B2024-581-02
- Conditions
- Nasopharyngeal Cancinoma (NPC)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 21 Oct 2024 (actual)
- Primary completion
- 21 Oct 2025 (estimated)
- Study completion
- 21 Oct 2026 (estimated)
- First posted
- 30 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With the advancement of large-scale phase III clinical studies such as RATIONALE-309, JUPITER-02, and CAPTAIN-1, the GP regimen combined with immunotherapy has become the recommended first-line treatment for recurrent metastatic nasopharyngeal carcinoma. However, patients receiving first-line chemotherapy plus immunotherapy have a median progression-free survival time of only 9.6 to 21.4 months, indicating that disease progression is still inevitable after first-line chemo-immunotherapy in patients with recurrent/metastatic nasopharyngeal carcinoma. Therefore, second or subsequent line treatment options are crucial for the management of patients with recurrent/metastatic nasopharyngeal carcinoma.
In 2021, the International Society for Cancer Immunotherapy reported a multicenter, open-label, single-arm phase II clinical study of cadonilimab in patients with metastatic nasopharyngeal carcinoma who had failed second-line or subsequent chemotherapy. The data showed that among the 20 evaluable patients enrolled, the objective response rate for cadonilimab monotherapy reached 30%, with a disease control rate of 70%, and the median progression-free survival time was 3.71 months. These study results suggest that cadonilimab demonstrates encouraging anti-tumor activity and good safety in patients with metastatic nasopharyngeal carcinoma who have failed second-line or subsequent chemotherapy.
Detailed description
Cadonilimab (AK104) is humanized bispecific antibody that targets to PD-1 and CTLA-4 . Its tetravalent and no Fc binding design contribute to its high binding activity in the tumor microenvironment and improved safety profile . Recent studies have shown encouraging efficacy and manageable toxicity of cadonilimab in several different cancer types. Cadonilimab monotherapy has shown an ORR of 30% and disease control rate (DCR) of 70%, with the median disease-free survival time of 3.71 months in patients with RM-NPC at the second line setting. There is no study available to explore the role of cadonilimab in anti-PD-1 resistant RM NPC patients.
Our previous study prospectively proven the superiority of TPC regimen (paclitaxel, cisplatin, and capecitabine) versus cisplatin and fluorouracil (PF) as induction treatment for patients with stage IVA NPC in NPC patients. Besides, after achieved disease control from TPC regimen induce therapy, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC with tolerate toxic . These results suggest the promising application prospect of TPC regimen in RM-NPC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TPC chemotherapy | Active comparator | Drug: TPC chemotherapyNAB-paclitaxel; cisplatin or lobaplatin and capecitabine |
| Cadonilimab with TPC chemotherapy | Experimental | Drug: cadonilimab combined TPC chemotherapycadonilimab plus TPC chemotherapy (NAB-paclitaxel, cisplatin or lobaplatin ; and capecitabine |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 1.Histopathological diagnosis confirmed as non-keratinizing nasopharyngeal carcinoma.
- 2.Confirmed diagnosis of metastatic or recurrent nasopharyngeal carcinoma, not suitable for radical local treatment.
- 3.Patients who have failed first-line or subsequent anti-PD-1 antibody immunotherapy (either monotherapy or combination therapy).
- 4.Age between 18 and 70 years. 5.Generally good condition, ECOG score of 0-1, with a life expectancy of ≥3 months.
- 6.At least one measurable lesion (according to RECIST 1.1); lesions that have been previously irradiated can be considered target lesions if imaging diagnosis clearly shows progression and they are measurable.
Key exclusion criteria (8 listed)
- 1.History of hypersensitivity to monoclonal antibodies. 2.Time interval of less than 6 months from the last first-line TPC chemotherapy.
- 3.Known history of interstitial pneumonia. 4.Severe infection occurring within 4 weeks prior to the first administration, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
- 5.Patients who have used aspirin (>325 mg/day) or dipyridamole, ticlopidine, clopidogrel, and cilostazol within 3 weeks prior to medication, or anticoagulants requiring INR monitoring (such as warfarin), or those who have received any blood components and cell growth factor support therapy within 1 week prior to medication.
- 6.Active infections requiring systemic treatment. 7.Active hepatitis B (HBV-DNA ≥ 1000 IU/ml) that persists despite treatment, excluding those with cured hepatitis C; significant clinical bleeding symptoms or a clear bleeding tendency within 1 month prior to medication.
- 8.Received the last radiotherapy or antitumor treatment within 3 weeks prior to the first administration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TPC chemotherapyAlso: NAB-paclitaxel, cisplatin, and capecitabineThe TPC regimen included NAB-paclitaxel administered at a dose of 200 mg/m2 on day 1, cisplatin at a dose of 60 mg/m2 on day 1, and capecitabine at a dose of 1000 mg/m2, taken orally twice a day on days 1 to 14, for each cycle | Drug | TPC chemotherapy |
| cadonilimab combined TPC chemotherapyAlso: cadonilimab combined NAB-paclitaxel, cisplatin, and capecitabineCadonilimab was intravenously given at dose of 10 mg/kg on day 1. The TPC regimen included NAB-paclitaxel administered at a dose of 200 mg/m2 on day 1, cisplatin at a dose of 60 mg/m2 on day 1, and capecitabine at a dose of 1000 mg/m2, taken orally twice a day on days 1 to 14, for each cycle | Drug | Cadonilimab with TPC chemotherapy |
Primary outcome
progression-free survival
Time frame: from the enrollment to disease progression or death from any cause, assessed up to 12 months
The primary endpoint was PFS, which was assessed as the time from randomization to disease progression per RECIST v1.1 assessed by IRC or death, whichever occurred first.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TPC chemotherapy and cadonilimab combined TPC chemotherapy in people with Nasopharyngeal Cancinoma (NPC), run by Sun Yat-sen 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 8 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 30 Oct 2024. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival (time frame: from the enrollment to disease progression or death from any cause, assessed up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Oct 2024.