A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of KTN3379 in Adult Subjects With Advanced Tumors

Study Overview
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Brief Summary
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Part I will evaluate the pharmacokinetic profile and safety of KTN3379 over several doses with the objective of defining a Phase 2 dose in patients with advanced malignancies. Part II will evaluate the pharmacokinetic profile and safety of KTN3379 in combination with other targeted agents and obtain preliminary evidence of anti tumor activity in specific types of cancer. Patients will continue receiving KTN3379 alone or in combination until disease progression or toxicity that necessitates discontinuation (whichever comes first).

Official Title
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Part I and Part II A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of KTN3379 in Adult Subjects With Advanced Tumors Alone or With Chemotherapy

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: KTN3379


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Part I Histologically- or cytologically-confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exist. Part II Arm A have head and neck cancer or K-Ras wild type EGFR expressing colon cancer, Arm B, have non small cell lung cancer, Arm C, have BRAF V600E mutated melanoma and Arm D have HER2 positive breast or gastric cancer that has progressed following one or more treatments for advanced or metastatic disease. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Adequate organ function as defined below: Hemoglobin ≥ 9 g/dL Absolute neutrophil count ≥ 1500/mm3 Platelet count ≥ 100,000/mm3 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × institutional upper limit of normal (ULN) for cases involving liver metastasis and ≤ 2.5 ×ULN for all other cases Bilirubin ≤ 1.5 × ULN except for cases of documented or suspected Gilbert's disease, in which bilirubin must be ≤ 5 × ULN Serum creatinine ≤ 1.5 g/dL Measurable disease by RECIST Females must be surgically sterile, one year post menopausal or negative results for a pregnancy test performed at Screening and agree to use two methods of contraception; Males who have not had a vasectomy must agree to two methods of contraception Major Exclusion Criteria: Receipt of anticancer therapy: within 3 weeks prior to the first dose of KTN3379, or within 6 weeks or 7 half lives prior to the first dose of KTN3379 in the case of anticancer therapy involving MAbs, or within 2 weeks prior to the first dose of KTN3379 in the case of palliative radiation therapy. Symptomatic or untreated central nervous system metastases requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids; if treated, subject must be asymptomatic for 3 months prior to study entry Subjects who are known to have a history of or active human immunodeficiency virus (HIV) or active hepatitis B and/or C Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled or idiopathic hypotension, unstable angina pectoris, cardiac arrhythmia including atrial fibrillation, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results Subjects with a left ventricular cardiac ejection fraction < 50% as assessed by an echocardiogram or MUGA scan

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KTN3379<br>KTN3379 | Biological: KTN3379<br>* Single agent KTN3379 or in combination administered until unacceptable toxicity or progressive disease<br>|
| Experimental: Part II, Arm A<br>Combination of KTN3379 and cetuximab | Biological: KTN3379<br>* Single agent KTN3379 or in combination administered until unacceptable toxicity or progressive disease<br>|
| Experimental: Part II, Arm B<br>Combination of KTN3379 and erlotinib | Biological: KTN3379<br>* Single agent KTN3379 or in combination administered until unacceptable toxicity or progressive disease<br>|
| Experimental: Part II, Arm C<br>Combination of KTN3379 and vemurafenib | Biological: KTN3379<br>* Single agent KTN3379 or in combination administered until unacceptable toxicity or progressive disease<br>|
| Experimental: Part II, Arm D<br>Combination of KTN3379 and trastuzumab | Biological: KTN3379<br>* Single agent KTN3379 or in combination administered until unacceptable toxicity or progressive disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities for KTN3379 alone or in combination | Continued assessment of safety | Participants will be followed for the duration of treatment, an expected average of 3 cycles/9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve (AUC 0 through end of study) |  | Prior to the initial dose on day 1 through duration of treatment, an expected average of 3 cycles/9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KTN3379, Advanced cancer, Phase 1, Monoclonal antibody, Safety and pharmacokinetics, CDX3379