Chidamide in Combination With Toripalimab and Anlotinib in Recurrent/Metastatic Nasopharyngeal Carcinoma.

NCT ID: NCT07320963

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-02-28

Brief Summary

To explore and evaluate the dose-limiting toxicity (DLT) profile of the fixed-dose combination of toripalimab, anlotinib, and chidamide in patients with recurrent/metastatic nasopharyngeal carcinoma (R/M NPC), and to determine the maximum tolerated dose (MTD) of chidamide, thereby informing subsequent clinical dosing regimens.

To assess the objective response rate (ORR) of the combination regimen in this patient population.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chidamide , Toripalimab and Anlotinib

Group Type: EXPERIMENTAL

Chidamide

Intervention Type: DRUG

Phase Ib: Dose selection based on study progression (15 mg, 20 mg, or 30 mg). Phase II: PR2D Timing: Orally 30 minutes after dinner, twice weekly (e.g., Days 1, 4, 8, 11, 15, 18 of each 3-week cycle), with ≥3 days between doses.

Duration: Until disease progression or unacceptable toxicity, up to 24 months.

Toripalimab

Intervention Type: BIOLOGICAL

Fixed Dose: 240 mg per infusion. Timing: Intravenous infusion over 30 minutes on Day 1 of each 3-week cycle. Duration: Until disease progression or unacceptable toxicity, up to 24 months.

Anlotinib

Intervention Type: DRUG

Timing: Orally once daily before breakfast, Days 1-14 of each 3-week cycle. Duration: Until disease progression or unacceptable toxicity, up to 24 months.

Interventions

Chidamide

Phase Ib: Dose selection based on study progression (15 mg, 20 mg, or 30 mg). Phase II: PR2D Timing: Orally 30 minutes after dinner, twice weekly (e.g., Days 1, 4, 8, 11, 15, 18 of each 3-week cycle), with ≥3 days between doses.

Duration: Until disease progression or unacceptable toxicity, up to 24 months.

Intervention Type: DRUG

Toripalimab

Fixed Dose: 240 mg per infusion. Timing: Intravenous infusion over 30 minutes on Day 1 of each 3-week cycle. Duration: Until disease progression or unacceptable toxicity, up to 24 months.

Intervention Type: BIOLOGICAL

Anlotinib

Timing: Orally once daily before breakfast, Days 1-14 of each 3-week cycle. Duration: Until disease progression or unacceptable toxicity, up to 24 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Age: ≥18 years and ≤70 years, gender unrestricted. 2. Diagnosis: Histologically/pathologically confirmed metastatic nasopharyngeal carcinoma (NPC) that has failed at least one prior line of therapy (including cisplatin-containing regimens) or is intolerant to existing therapies (relapse within 6 months after completion of adjuvant/neoadjuvant concurrent chemoradiotherapy is eligible).

3. Performance Status: ECOG performance status 0-1. Measurable Disease: At least one measurable lesion per RECIST 1.1 criteria. 4. Prior Immunotherapy:

Patients who have received PD-1, PD-L1, PD-L2, or CTLA-4 inhibitors, or other therapies targeting T-cell co-stimulation/checkpoint pathways:

Must have achieved complete response (CR), partial response (PR), or stable disease (SD) ≥6 months during treatment.

Only one prior immunotherapy regimen is allowed (e.g., neoadjuvant and adjuvant regimens using the same immunotherapy are considered one regimen).

Switching to a different immunotherapy regimen for non-immunotherapy-related progression is permissible if cumulative SD duration ≥6 months.

6. Organ Function:

Hematology:

ANC ≥1.5×10⁹/L, PLT ≥75×10⁹/L, Hb ≥90 g/L. No blood product transfusion or growth factor support (e.g., G-CSF, EPO) within 2 weeks prior to screening.

Hepatology:

TBIL ≤1.5×ULN; ALT/AST ≤2.5×ULN (≤5×ULN if liver metastases present).

Renal Function:

Serum Cr ≤1.5×ULN or CrCl >60 mL/min.

Thyroid Function:

TSH, FT4, FT3 within CTC AE Grade 0-1. 7. Survival Expectancy: ≥3 months. 8. Informed Consent: Voluntary participation and signed written informed consent.

Exclusion Criteria

1. Known severe hypersensitivity (≥Grade 3) to any monoclonal/polyclonal antibody, chidamide, or anlotinib components.

2. Necrotic lesions identified within 4 weeks prior to enrollment, with investigator-judged risk of major bleeding.

3. Chemotherapy, targeted therapy, or immunomodulatory agents (including thymosin, interferon, IL-2, etc.) within 2 weeks prior to enrollment.

Washout period determined by clinical resolution of adverse events (AEs) and prior treatment regimens.

4. Palliative radiotherapy to localized lesions within 4 weeks prior to enrollment, unless the lesion is non-target and other measurable target lesions exist.

5. Grade ≥3 irAEs during prior immunotherapy.

6. Prior treatment with HDAC inhibitors or anti-angiogenic agents.

7. Urine protein ≥2+ or 24-hour urinary protein ≥1 g.

8. Systolic BP >140 mmHg or diastolic BP >90 mmHg despite treatment.

9. Persistent toxicity from prior antitumor therapy (per NCI CTCAE v5.0) >Grade 1, excluding: alopecia, Grade 2 fatigue, Grade 2 anemia, or asymptomatic lab abnormalities.

10. Symptomatic CNS metastases (e.g., edema, steroid requirement) or leptomeningeal disease.

11. Systemic immunosuppressive drugs (excluding topical/inhaled corticosteroids or physiological doses ≤10 mg/day prednisone equivalent) or corticosteroids for contrast allergy within 4 weeks prior to enrollment.

12. Active autoimmune diseases (e.g., interstitial pneumonia, colitis, thyroiditis) or history of severe autoimmune conditions requiring systemic therapy.

Exceptions: Vitiligo, childhood asthma (resolved without treatment), or mild asthma managed without bronchodilators.

13. Ongoing anti-tuberculosis therapy or treatment within 1 year prior to screening.

14. Conditions requiring long-term immunosuppressive therapy or systemic corticosteroids at immunosuppressive doses.

15. Severe Cardiac Disease or Significant Cardiac Symptoms.

16. Other Circumstances Deemed Unsuitable by the Investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Huiqiang Huang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Huiqiang Huang

Role: CONTACT

huanghq@sysucc.org.cn

020-87343350

Other Identifiers

CSIIT-Q113

Identifier Type: -

Identifier Source: org_study_id