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

NCT04925947 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-08022493
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Thymic Carcinoma

Outcome Measures

Primary Outcomes (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

  Up to 8 weeks

Secondary Outcomes (5)

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

  Up to 8 weeks

• 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.

  Up to 8 weeks

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

  Up to 8 weeks

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

  Up to 8 weeks

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

  Up to 8 weeks

Study Arms (1)

KN046

EXPERIMENTAL

KN046 will be given intravenously every 2 weeks.

Drug: KN046

Interventions

KN046 DRUG

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.

KN046

Eligibility Criteria

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

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Thymoma

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

This study was terminated early and participant enrollment was low, resulting in a small sample size (N=4). Having a small sample size may reduce statistical reliability and generalizability of results.

Results Point of Contact

• Title: Barbara Ma
• Organization: Weill Cornell Medicine

btm9003@med.cornell.edu

646-962-6444

Study Officials

• Barbara Ma, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 14, 2021
• Study Start: December 13, 2021
• Primary Completion: May 5, 2023
• Study Completion: May 5, 2023
• Last Updated: April 16, 2024
• Results First Posted: April 16, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)