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

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

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).

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Biological: KTN3379

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Perelman School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): May 25, 2017
• Study Completion (Actual): June 5, 2017

Study Registration Dates

• First Submitted: December 4, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 18, 2013

Study Record Updates

• Last Update Posted (Actual): July 24, 2017
• Last Update Submitted That Met QC Criteria: July 21, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Advanced cancer; Phase 1; Safety and pharmacokinetics; KTN3379; CDX3379
• Other Study ID Numbers: KTN3379-CL-001