JAK1 Inhibitor Ivarmacitinib Reversing Immunotherapy Resistance in TNBC

NCT06731153 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC-N085
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, randomized phase II clinical study which recruits unresectable recurrent or metastatic triple-negative breast cancer resistant to immunotherapy.

Conditions

Triple Negative Breast Cancer (TNBC); Metastatic Breast Cancer

Keywords

immune resistance; JAK1 inhibitor; triple negative breast cancer

Outcome Measures

Primary Outcomes (4)

• Safety run-in: Incidence rate of dose-limiting toxicities (DLTs)

  Incidence rate of DLT will be evaluated in participants in the Safety Run-In, who will be followed for protocol-defined DLT events up to 21±3 days after the first dose of Ivarmacitinib + Camrelizumab + Eribulin.

  21±3 days

• Safety run-in: adverse events (AEs)

  Incidence rate of AEs of any cause will be evaluated in participants in the Safety Run-In according to CTCAE v5.0.

  21±3 days

• Safety run-in: Serious adverse events (SAEs)

  Incidence rate of SAEs of any cause will be evaluated in participants in the Safety Run-In according to CTCAE v5.0.

  21±3 days

• Objective response rate (ORR)

  Defined as the proportion of patients with complete response (CR) and partial response (PR) by magnetic resonance imaging (MRI) or Computed Tomography (CT) according to RECIST v1.1.

  The observation period related to this endpoint is up to 12 months.

Secondary Outcomes (5)

• Disease control rate (DCR)

  The observation period related to this endpoint is up to 12 months.

• Duration of Response (DOR)

  The observation period related to this endpoint is up to 12 months.

• Progression Free Survival (PFS)

  The observation period related to this endpoint is up to 12 months.

• Overall Survival (OS)

  The observation period related to this endpoint is up to 24 months.

• Treatment-Related Toxicity Rate

  The observation period related to this endpoint is up to 12 months.

Study Arms (3)

Safety run-in

EXPERIMENTAL

Ivarmacitinib + Camrelizumab + Eribulin

Drug: Ivarmacitinib; Drug: Camrelizumab (SHR-1210); Drug: Eribulin

Treatment group

EXPERIMENTAL

Ivarmacitinib + Camrelizumab + Eribulin, RP2D

Drug: Ivarmacitinib; Drug: Camrelizumab (SHR-1210); Drug: Eribulin

Control group

ACTIVE COMPARATOR

Ivarmacitinib + Eribulin, RP2D

Drug: Ivarmacitinib; Drug: Eribulin

Interventions

Ivarmacitinib DRUG

a selective Janus kinase 1 inhibitor

Control group; Safety run-in; Treatment group

Camrelizumab (SHR-1210) DRUG

a humanised anti-programmed death-1 (anti PD-1) antibody

Safety run-in; Treatment group

Eribulin DRUG

Eribulin is an anticancer drug approved for treatment of metastatic breast cancer. This drug is a synthetic derivative from Japanese marine sponge Halichondria okadai. It acts by interfering with the microtubular growth ultimately leading to apoptosis after prolonged mitotic blockage.

Control group; Safety run-in; Treatment group

Eligibility Criteria

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

You may qualify if:

• Age 18-70 years old (both ends included);
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0,1, 2;
• Metastatic or locally advanced, histologically documented TNBC;
• Histologically confirmed diagnosis of TNBC characterized by estrogen-receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor-2 receptor negative (HER2-);
• Radiologic/objective evidence of recurrence or disease progression after immunotherapy (anti-PD-1/PD-L1 antibodies) for metastatic breast cancer (MBC);
• For patients refractory/resistant to anti-PD-1/PD-L1 antibodies, there should be no anti-PD-1/PD-L1 treatment-related toxicity from prior therapies;
• Participants must have measurable disease per RECIST 1.1;
• Life expectancy ≥3 months;
• The functions of the main organs are basically normal and meet the following conditions:
• I. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 10\^9 / L; PLT acuity 90 x 10\^9 / L; II. Biochemical tests should meet the following criteria: Albumin ≥3.0 g/dL; TBIL≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula); International Normalized ratio (INR)≤ 1.5 or prothrombin time ≤1.5 times ULN; Activated partial thromboplastin time (aPTT)≤1.5 times ULN III. Male QTcF ≤450 msec, female QTcF ≤470 msec; LVEF≥50%;
• They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity;
• Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug;
• Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.

You may not qualify if:

• Active brain metastases, cancerous meningitis, primary central nervous system (CNS) tumors not treated with surgery or radiotherapy; Stable for at least 4 weeks after treatment and corticosteroid discontinuation \>2 weeks can be included;
• History of active autoimmune disease or autoimmune disease that may recur (excluding well-controlled type 1 diabetes, hypothyroidism (which can be controlled with hormone replacement therapy only), well-controlled celiac disease, skin diseases that do not require systemic treatment (e.g. Vitiligo, psoriasis, alopecia) , any other disease that is not expected to recur without an external trigger);
• Have previously received Eribulin;
• Any active malignancies ≤2 years prior to first administration of the drug, except for the specific cancers studied in this trial and any locally recurrent cancers that have been treated with radical treatment (such as resected basal cell or squamous cell skin cancer, cervical or breast carcinoma in situ);
• Have an active autoimmune disease, or a disease requiring systemic steroid hormone or immunosuppressive drug treatment, or other acquired (HIV infection), congenital immunodeficiency disease, or a history of organ transplantation (including allogeneic bone marrow transplantation);
• Corticosteroids ≤14 days before the first administration of the study drug;
• Uncontrolled diabetes mellitus, ≥grade 3 hypoalbuminemia, or laboratory tests were present ≤14 days before the first administration of the study drug or \>Grade 1 abnormalities in blood potassium, sodium, or calcium despite standard drug therapy;
• History of interstitial lung disease, non-infectious pneumonia, or uncontrolled disease, including pulmonary fibrosis and acute lung disease;
• Severe chronic or active infections (including tuberculosis, etc.) requiring systemic antimicrobial, antifungal, or antiviral therapy within 14 days prior to the first administration of the drug. Note: Antiviral therapy is allowed for patients with viral hepatitis
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \> 500 IU/mL) or active HCV carriers with detectable HCV RNA. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA \< 500 IU/mL) can be enrolled;
• Any major surgery requiring general anesthesia ≤28 days before the first administration of the drug;
• Previous allogeneic stem cell transplantation or organ transplantation;
• Any of the following cardiovascular criteria
• The presence of cardiogenic chest pain ≤28 days
• The presence of symptomatic pulmonary embolism ≤28 days

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Breast cancer institute of Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

ivarmacitinib; camrelizumab; eribulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 12, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)