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

A Prospective, Single-Arm, Phase Ib/II Clinical Trial of Chidamide in Combination With Toripalimab and Anlotinib in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma Who Have Failed at Least One Prior Line of Therapy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Chidamide; Biological: Toripalimab; Drug: Anlotinib

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Huiqiang Huang; Phone Number: 020-87343350; Email: huanghq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

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

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: Chidamide , Toripalimab and Anlotinib

Drug: 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.; Biological: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	2 years
MTD	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS)	2 years
Overall Survival (OS)	2 years
Duration of response (DoR)	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Fujian Cancer Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2026
• Primary Completion (Estimated): March 28, 2027
• Study Completion (Estimated): March 28, 2028

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 22, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NPC; PD-1 antibody; chidamide; anti-angiogenesis; HDACi
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; anlotinib; toripalimab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
• Other Study ID Numbers: CSIIT-Q113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No