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Triple Negative Breast Cancer (TNBC)Phase 2NCT06731153

JAK1 Inhibitor Ivarmacitinib Reversing Immunotherapy Resistance in TNBC

A Phase 2 study testing Ivarmacitinib, Camrelizumab (SHR-1210) and Eribulin in people with Triple Negative Breast Cancer (TNBC) and Metastatic Breast Cancer, run by Fudan University at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Ivarmacitinib, Camrelizumab (SHR-1210) and Eribulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteChina
Study dates
Dec 2024to Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • 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;
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  • 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:
  • 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.

Who cannot join

  • 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;
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  • 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
  • Active psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, etc.). Depression being treated with antidepressants is not an exclusion criterion;
  • 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
  • To investigate any history of acute myocardial infarction ≤6 months
  • A history of heart failure ≤6 months at any New York Heart Association (NYHA) grade III or IV
  • Presence of any ventricular arrhythmia event ≤6 months of grade 2 or greater severity
  • Any history of cerebrovascular accidents ≤6 months
  • Corrected QT Interval (QTc)(corrected by Fridericia method) >450 ms.
  • Any syncope or seizure that occurred ≤28 days;
  • Poorly controlled hypertension (defined as: systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg)
  • Hypersensitivity to ivarmacitinib or to any component of containers;
  • Systemic chemotherapy within 28 days of initial administration of the investigational drug or immunotherapy (e.g., interleukin, interferon, thymosin, etc.), hormone therapy, targeted therapy, or any investigational therapy within 14 days of initial administration of the investigational drug or within 5 half-lives, whichever is shorter;
  • Use of any Chinese herbal medicine or proprietary Chinese medicine with anti-cancer activity approved by the National Drug Administration (NMPA) within 14 days prior to first administration of the investigational drug (regardless of cancer type);
  • Toxicity from previous anticancer therapy has not improved to baseline or stabilized, except for AEs not considered a safety risk (e.g., hair loss, neuropathy, and specific laboratory abnormalities);
  • Have received live vaccine ≤28 days before. Note: Seasonal influenza vaccine is an inactivated vaccine in a broad sense and is allowed to be used. Intranasal influenza vaccine is a live vaccine and should not be used;
  • An underlying medical condition (including laboratory abnormalities), alcohol or drug abuse or dependence that impedes study drug administration or interferes with interpretation of study drug toxicity and AE, or results in inadequate or reduced adherence to the study;
  • Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventional study;
  • Inability to swallow capsules or diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, total stomach or small intestine resection, bariatric surgery, inflammatory bowel disease, or incomplete or complete intestinal obstruction;
  • Uncontrolled pleural effusion, pericardial effusion, or abdominal effusion requiring frequent drainage or medical intervention within 7 days of first administration of the drug (clinically significant recurrence requiring additional intervention within 2 weeks after intervention, excluding exudate cytological testing);
  • Pregnant or lactating women.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site

  • Breast cancer institute of Fudan University Cancer Hospital

    Shanghai, Shanghai Municipality, 200032

Other trials in China

About this study

Official title: A Randomized, Controlled, Open-label, Phase II Clinical Study Evaluating the JAK1 Inhibitor Ivarmacitinib to Reverse Immunotherapy Resistance in Triple-negative Breast Cancer

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

Read the detailed description

This is a prospective, open-label, randomized phase II clinical study. The purpose of this study is to test the combination of the JAK1 inhibitor Ivarmacitinib and the PD-1 inhibitor Camrelizumab in patients with immunotherapy-resistant locally advanced inoperable or metastatic triple-negative breast cancer. The study included a safety run-in period to explore the safety of Ivarmacitinib in combination with Eribulin and Camrelizumab, which will provide a recommended dose for the triplet combination of Ivarmacitinib, Camrelizumab and Eribulin. The latter phase II period is set to compare the efficacy of the triplet combination of Ivarmacitinib, Camrelizumab and Eribulin versus Eribulin plus Ivarmacitinib.

Being tested
Ivarmacitinib, Camrelizumab (SHR-1210), Eribulin
Keywords
immune resistance, JAK1 inhibitor, triple negative breast cancer
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvarmacitinibDrug

    a selective Janus kinase 1 inhibitor

  • Camrelizumab (SHR-1210)Drug

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

  • EribulinDrug

    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.

Study groups in NCT06731153
Study groupRoleWhat they receive
Safety run-inExperimentalIvarmacitinib + Camrelizumab + Eribulin
Receives: Drug: Ivarmacitinib; Drug: Camrelizumab (SHR-1210); Drug: Eribulin
Treatment groupExperimentalIvarmacitinib + Camrelizumab + Eribulin, RP2D
Receives: Drug: Ivarmacitinib; Drug: Camrelizumab (SHR-1210); Drug: Eribulin
Control groupActive comparatorIvarmacitinib + Eribulin, RP2D
Receives: Drug: Ivarmacitinib; Drug: Eribulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 21±3 days

  2. 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.

    Measured: 21±3 days

  3. 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.

    Measured: 21±3 days

  4. 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.

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

Secondary outcomes (5)

  1. Disease control rate (DCR)

    Defined as the proportion of participants with CR and PR as the best overall response.

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

  2. Duration of Response (DOR)

    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause). Participants without reported events are censored at the last disease evaluation.

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

  3. Progression Free Survival (PFS)

    PFS based on Kaplan-Meier methodology will be defined as the time from randomization until the identification of disease progression or death, whichever occurs first. Subjects without disease progression or death at the time of analysis will be censored at the date of last disease evaluation.

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

  4. Overall Survival (OS)

    Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

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

  5. Treatment-Related Toxicity Rate

    The percentage of participants who experienced any grade treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.

    Measured: The observation period related to this endpoint is 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.

  1. First posted12 Dec 2024
  2. Study startDec 2024 (estimated)
  3. Primary completionJun 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06731153
Sponsor's protocol ID
SCHBCC-N085
Status last verified
Dec 2024
First submitted
9 Dec 2024
Last updated
12 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ivarmacitinib, Camrelizumab (SHR-1210) and Eribulin in people with Triple Negative Breast Cancer (TNBC) and Metastatic Breast Cancer, run by Fudan 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 13 inclusion and 33 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: opening soon, as of the sponsor's last update on 12 Dec 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Safety run-in: Incidence rate of dose-limiting toxicities (DLTs) (time frame: 21±3 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06731153.

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 12 Dec 2024.

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