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

Sponsor

Celldex Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT02014909

Collaborator

(none)

Enrollment

Locations

Arms

41.1

Duration (Months)

12.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer	Biological: KTN3379	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

64 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2014

Actual Primary Completion Date :

May 25, 2017

Actual Study Completion Date :

Jun 5, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Dose limiting toxicities for KTN3379 alone or in combination [Participants will be followed for the duration of treatment, an expected average of 3 cycles/9 weeks]
Continued assessment of safety

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarah Cannon Research Institute	Denver	Colorado	United States	80218
2	Yale Cancer Center	New Haven	Connecticut	United States	06511
3	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	University of Pennsylvania Perelman School of Medicine	Philadelphia	Pennsylvania	United States	19104
5	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203