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Thymic CarcinomaPhase 2NCT04925947

A Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors

A Phase 2 study testing KN046 in people with Thymic Carcinoma, run by Weill Medical College of Cornell University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will assess the safety and efficacy of the study drug KN046 in patients with advanced thymic carcinoma who progressed after prior treatment with immune checkpoint inhibitor therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thymic Carcinoma
What is being tested?
KN046
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
13 Dec 2021to 5 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent form.
  • Male or female, 18 years of age or older; willing and able to complete all required procedures of study.
  • Pathologically confirmed diagnosis of thymic carcinoma; a tumor sample is required for confirmation of pathological diagnosis and further studies on the tumor tissue.
  • Inoperable or metastatic disease.
  • Progressive disease documented in the last 6 months.
  • Has failed platinum-based chemotherapy, with progression either during or after treatment.
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  • Had failed at least one regimen of systemic therapy containing immune checkpoint blockade therapy targeting PD-1, PD-L1, or CTLA-4 for locally advanced unresectable or metastatic disease. Subjects should have documented progressive disease while or after an immune checkpoint therapy. If subjects discontinued therapy due to reasons other than progressive disease, subjects should have completed at least 2 cycles of immune checkpoint therapy.
  • Baseline measurable disease according to RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • ECOG performance status of 0 or 1.
  • Adequate organ function assessed within 7 days prior to first trial treatment:
  • Hematological function:
  • ANC≥1.5 x 109/L; Hemoglobin≥9 g/dL; Platelets≥100 x 109/L
  • Renal function:
  • Calculated creatinine clearance≥60 mL/min (Cockcroft-Gault method)
  • Hepatic function:
  • Total bilirubin≤1.5 x ULN (or 2.5 x ULN for documented Gilberts' syndrome); ALT/AST≤3.0 x ULN (or 5.0 x ULN for documented liver metastasis); INR or aPTT ≤1.5 x ULN
  • Have a life expectancy of at least 3 months.
  • If female of childbearing potential, have a negative serum pregnancy test within 7 days prior to first trial treatment.
  • If female of childbearing potential or a male subject with a partner with childbearing potential, be willing to use a highly effective method of contraception (with a failure rate of less than 1.0% per year) from first study treatment to 24 weeks after completion of the trial treatment.

Who cannot join

  • Thymomas, thymolipoma, germ cell tumors, teratomas, seminomas.
  • Leptomeningeal metastasis or untreated active CNS metastasis or leptomeningeal metastasis. Subjects with CNS metastasis may be eligible provided they are treated and clinically stable for at least 4 weeks and have no evidence of new or enlarging brain metastases and also are off steroids 7 days prior to first trial treatment.
  • Is currently participating and receiving an investigational drug or has participated in a study of an investigational drug within 4 weeks or within 5 times of half-life (no less than 2 weeks), whichever is shorter, prior to the first dose of trial treatment.
  • Major surgery for any reason, except diagnostic biopsy, within 4 weeks of the first administration of trial treatment and/or if the subject has not fully recovered from the surgery within 4 weeks of the first administration of trial treatment.
  • Radiation within 4 weeks prior to the first administration of trial treatment; palliative radiation will be allowed if more than 2 weeks before start of KN046 treatment.
  • Subjects receiving immunosuppressive agents (such as systemic steroids); topical use of steroids and steroid inhalers are allowed. Replacement therapy because of adrenal insufficiency is also allowed.
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  • Vaccination within 28 days of the first administration of trial treatment, except for administration of inactivated vaccines (e.g., inactivated influenza vaccines).
  • Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
  • History or current active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, including but not limited to:
  • Myasthenia gravis (MG), Good syndromes, ISAACS syndromes, polymyositis, myocarditis, neuromuscular syndrome (myotonic dystrophy myositis, Eaton-Lambert syndrome), blood disorders (red cell aplasia, hypogammaglobulinemia, T-cell deficiency syndrome, erythrocytosis, pancytopenia, megakaryocytopenia, T-cell lymphocytosis, pernicious anemia), systemic lupus erythematosus, sarcoidosis, scleroderma, Crohn's disease, inflammatory bowel disease, Wegener syndrome (granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis), autoimmune hepatitis, systemic sclerosis (for example scleroderma), Hashimoto thyroiditis (with the exception as stated below), hyperparathyroidism, stiff-person syndrome, Addison disease, panhypopituitarism, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome) etc.
  • NOTE: Subjects with Type I diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease, Sjögren syndrome not requiring immunosuppressive treatment are eligible. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg or equivalent prednisone per day. Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) are acceptable.
  • Previous malignant disease other than the target malignancy to be investigated in this study with the exception of adequately treated non-melanomatous cancers of the skin, in situ carcinoma of the prostate/cervical/breast cancer, or other malignancy treated at least 5 years previously with surgery and/or curative radiotherapy, and there is no evidence of recurrence since that time.
  • History of uncontrolled intercurrent illness including but not limited to: Active HBV or HCV infection (If HBsAg and HCV antibody positive, HBV DNA and HCV RNA assay should be performed. Subjects may be eligible if HBV DNA ≤ 500 UI/ml (or 2000 copies/ml) or HCV RNA negative); Known HIV infection or known history of acquired immune deficiency syndrome (AIDS); Active tuberculosis infection; Active infection within 2 weeks prior to the first dose of trial treatment that require the use of systemic antibiotics; Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg); Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class II-IV) or serious cardiac arrhythmia requiring medication (including corrected QT interval prolongation of > 470 msec calculated according to Fridericia and/or pacemaker or prior diagnosis of congenital long QT syndrome
  • Persisting toxicity related to prior therapy (including any prior investigational therapy) of CTCAE ≥ grade 2 (NCI-CTCAE v5.0) or related toxicity not recovery to baseline, with the exception of alopecia of any grade.
  • Prior allo-HSCT or solid organ transplant.
  • Known severe hypersensitivity reactions to antibody drug (≥ grade 3 NCI-CTCAE v5.0), any history of anaphylaxis, uncontrolled asthma (that is, 3 or more features of partially controlled asthma), or any history of severe drug hypersensitivity (for example immune mediated liver toxicity, immune mediated thrombocytopenia or anemia).
  • Is pregnant or breastfeeding.
  • Other medical conditions that at the discretion of investigator interfere with the requirements of the trial in terms of safety or efficacy evaluation, or treatment compliance. These include but are not limited to psychiatric or substance abuse disorder, moderate to large pleural fluid/cardiac effusion/ascites, or recurrent/refractory pleural fluid/cardiac effusion/ascites.
  • .Subjects with history or baseline positive antiacetylcholine receptor (AChR) autoantibody and anti-MuSK autoantibody.
  • Subjects who developed grade 3 or above immune related AE which could not be managed by steroid or immune suppressant will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medicine

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase II Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors

This study will assess the safety and efficacy of the study drug KN046 in patients with advanced thymic carcinoma who progressed after prior treatment with immune checkpoint inhibitor therapy.

Read the detailed description

Patients will receive KN046 intravenously at 5 mg/kg every 2 weeks until progression or excessive toxicity for up to to two years, with the goal of this trial to contribute to the development of active and well tolerated treatments for patients who have progressed on prior treatment therapies.

Recently, molecules that combine PD-1 and CTLA-4 have been developed for patients with lung cancer, with the hope that targeted therapy will be more effective than standard of care therapies. KN046 is believed to be less toxic than other targeted therapies with an assumption that the whole molecule can actively target tumor tissue for a much higher affinity of the anti-PD-L1 portion and a weaker affinity for anti-CTLA-4, leading to less autoimmune disorders and toxicities for patients than seen with other targeted therapies.

Being tested
KN046
Medical subject headings
Thymoma

What participants receive

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

  • KN046Drug

    KN046 will be given intravenously at 5 mg/kg every 2 weeks. A cycle is defined as 2 treatments (28 days). Treatment will be given until progression, excessive toxicity, or up to two years.

Study groups in NCT04925947
Study groupRoleWhat they receive
KN046ExperimentalKN046 will be given intravenously every 2 weeks.
Receives: Drug: KN046

What is being measured

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

  1. Anti-tumor Activity of KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria.

    Disease response rate

    Measured: Up to 8 weeks

Secondary outcomes (5)

  1. Safety of KN046 in Subjects With Thymic Carcinoma, Measured by the Number of Adverse Events That Occur in Subjects While Receiving Study Treatment.

    Measured: Up to 8 weeks

  2. Tolerability of KN046 in Subjects With Thymic Carcinoma, Measured by the Severity of Adverse Events That Occur in Subjects While Receiving Study Treatment, Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

    AEs are graded using the following criteria using Common Terminology Criteria for Adverse events v5.0:

    Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

    Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.

    Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.

    Grade 4: Life-threatening consequences; urgent intervention indicated.

    Grade 5: Death related to AE.

    Measured: Up to 8 weeks

  3. Duration of Response for KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria.

    Measured: Up to 8 weeks

  4. Progression Free Survival (PFS) for KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria.

    Measured: Up to 8 weeks

  5. Overall Survival (OS) for KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria.

    Measured: Up to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2021
  2. Study start13 Dec 2021
  3. Primary completion5 May 2023
  4. Study completion5 May 2023

Why it stopped: Data collected did not support the study endpoints

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04925947
Sponsor's protocol ID
20-08022493
Status last verified
Mar 2024
First submitted
8 Jun 2021
Last updated
16 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KN046 in people with Thymic Carcinoma, run by Weill Medical College of Cornell University at 1 site in United States.

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 19 inclusion and 20 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: stopped early, as of the sponsor's last update on 16 Apr 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 United States. 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?

Yes. Results are posted in the registry (first posted 16 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Anti-tumor Activity of KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria. (time frame: Up to 8 weeks). 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 NCT04925947.

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 16 Apr 2024.

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