Anti-PD-1 Antibody Combined With Histone Deacetylase Inhibitor in Patients With Advanced Cervical Cancer

NCT04651127 | Terminated Phase 1

• 1 other identifier: B2020-229-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. stage IVB), persistent, or recurrent cervical cancer. However, patients in this setting are rarely curable. Pembrolizumab has been approved for second-line treatment in patients with advanced PD-L1-positive cervical cancer. However, the response rate achieved by PD-1 inhibitors as monotherapy is only modest. Preclinical studies found that in mouse models of B-cell lymphoma, adding a histone deacetylase (HDAC) inhibitor sensitized cancers to anti-PD-1 therapy. Recently, combination treatment of HDAC inhibitors with immune checkpoint inhibitors is widely investigated and has promising results in several cancer types. Toripalimab is a humanized IgG4 monoclonal antibody against PD-1. Chidamide is a class I HDAC inhibitor. Here we conducted a phase Ib/II, single-arm, multi-center study to evaluate the efficacy and safety of toripalimab in combination with chidamide in patients with metastatic, persistent, or recurrent cervical cancer.

Conditions

Cervical Cancer; Cervix Cancer; Cervix Neoplasm

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of the combination of toripalimab and chidamide (Phase Ib)

  Dose-limiting toxicities (DLTs) are defined as: grade 3 febrile neutropenia, grade 4 hematologic toxicities, and grade 3 non-hematologic toxicities according to CTCAE v5.0

  first 28 days of treatment

• Objective Response Rate (ORR) (Phase II)

  ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  from the first drug administration up to two years

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  from the first drug administration up to two years

• Duration of response (DOR)

  from the first drug administration up to two years

• Disease Control Rate (DCR)

  from the first drug administration up to two years

• Overall survival (OS)

  from the first drug administration up to two years

• Safety and tolerability

  up to 90 days after last study treatment administration

Study Arms (1)

Toripalimab + Chidamide Arm

EXPERIMENTAL

Drug: Toripalimab + Chidamide

Interventions

Toripalimab + Chidamide DRUG

In combination dose finding phase, phase 1b will begin with Dose Level 1: chidamide 30 mg/day orally (twice a week) and toripalimab (240mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle. Two dose de-escalation steps are included: Dose Level 2 (chidamide 25 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously) and Dose Level 3 (chidamide 20 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously). If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week).

Toripalimab + Chidamide Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF).
• Patients must have histologically confirmed diagnosis of metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
• Age ≥ 18 years and ≤ 70 years.
• Patients must have measurable disease per RECIST v1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy exceeds 3 months.
• Patients must have progressed on at least one line of platinum-based systemic therapy.
• Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic cervical cancer. However, adjuvant chemotherapy could be counted as one prior regimen in patients who had recurrence during or within 6 months of completion of therapy.
• Patients must have adequate organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) (≥ 1.5×10\^9/L), hemoglobin of ≥ 90 g/L, platelets ≥ 80 ×10\^9/L
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
• Baseline albumin ≥ 28 g/L
• Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with free Triiodothyronine \[FT3\] or free Thyroxine \[FT4\] levels ≤ 1 × ULN may be enrolled)

You may not qualify if:

• Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to HDAC inhibitors.
• Any condition requiring systemic treatment with corticosteroids (\>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before first dose of study drug. Corticosteroids for topical use, nasal spray, and inhaled steroids are allowed.
• Active autoimmune diseases that require systemic treatment. Alternative treatments (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are permitted.
• Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association \[NYHA\] class \> 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
• Arterial or venous thrombosis within 6 months before enrollment
• Uncontrolled hypertension defined as systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg despite antihypertensive drugs.
• Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g.
• Coagulation abnormalities (INR \> 2.0, PT \> 16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
• Has known active central nervous system metastases.
• Patients had a diagnosed and/or treated additional malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has a known history of immunodeficiency including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
• Has known active Hepatitis B or Hepatitis C.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Centre

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

toripalimab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Xin Huang

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 3, 2020
• Study Start: November 9, 2020
• Primary Completion: January 26, 2023
• Study Completion: January 26, 2023
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

CN (1)