Phase 1 Study of CEP-37250/KHK2804 in Subjects With Advanced Solid Tumors

Two-Part, Open-Label, Multi-Center Phase 1 Study of Monoclonal Antibody CEP-37250/KHK2804 in Subjects With Advanced Solid Tumors

This is a two-part, Phase 1 open label, multi-center, dose escalation study of CEP-37250/KHK2804 as monotherapy in subjects with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Pancreas; Solid Tumour; Adenocarcinoma of the Colorectal
• Intervention / Treatment: Drug: CEP-37250/KHK2804

Detailed Description

The study will be conducted in two parts. In Part 1, a standard 3+3 designed dose escalation phase, subjects will receive CEP-37250/KHK2804, administered iv, once every week. A treatment cycle will consists of total of four doses per cycle. Part 2 of the study will enroll subjects with either colon cancer or pancreatic cancer to receive CEP-37250/KHK2804 at a dose to be determined following completion of Part 1.

All subjects will receive study therapy until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the subject, or Investigator decision, up to a maximum of six cycles (approximately six months). After six cycles of CEP-37250/KHK2804 therapy, the subject may continue to receive CEP-37250/KHK2804 after discussion with the Sponsor and determination that the subject is experiencing a best response of at least stable disease (SD) and is not experiencing any unacceptable toxicities or dose limiting toxicities (DLTs).

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

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

Inclusion Criteria:

• Adequate hepatic, renal, and hematologic function;
• Life expectancy > 3 months;
• Part 1 and 2: The subject has histopathologically or cytologically documented, measurable, unresectable, locally advanced primary or recurrent, metastatic solid tumor, locally advanced primary or recurrent, metastatic pancreatic adenocarcinoma and must have received at least one prior treatment regimen containing gemcitabine or 5-FU, and locally advanced primary or recurrent, metastatic colon adenocarcinoma.

Exclusion Criteria:

• Parts 1 and 2:

  1. Malignant melanoma, Merkel cell cancer, small cell lung cancer, lymphoepithelial carcinoma, malignant mesothelioma, GIST, Hodgkin and NHL, thymoma, neuroendocrine, neuronal tumors, and sarcomas. This list of excluded tumors may be modified as additional research findings become available on target antigen expression;
  2. The subject has received anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks (6 weeks for mitomycin C and nitrosoureas) prior to the first dose of CEP-37250/KHK2804;
  3. The subject has received monoclonal antibodies of any type or for any form of disease within 4 weeks of the first dose of CEP-37250/KHK2804;
  4. Major surgery within 4 weeks prior to the first dose;
  5. Known symptomatic brain metastases (screening magnetic resonance imaging (MRI) of the brain is only required when there is clinical suspicion of central nervous system [CNS] involvement or past history of treated brain metastasis). Subjects with treated brain metastasis (radiotherapy and/or surgery) will be eligible if they:
• Have completed treatment for their brain metastasis > 4 weeks prior to scheduled study treatment start date;
• Are neurologically stable;
• Are on corticosteroids in doses no greater than physiological replacement (e.g., dexamethasone < 1.5 mg/day); and
• Have a screening MRI scan of the brain that specifically verifies no evidence of CNS hemorrhage and no active gadolinium enhancing lesions;

• Subjects with primary brain/CNS malignancy (e.g., gliomas, lymphomas) are excluded.

  • Hypersensitivity reaction to monoclonal antibodies, other therapeutic proteins, or allergy to any component of the CEP-37250/KHK2804 finished drug and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-HT3 antagonists, or corticosteroids.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; Dose escalation in subjects with advanced solid tumors with Part 1 which includes intervention of CEP-37250/KHK2804	Drug: CEP-37250/KHK2804; Part 1 is based on the CEP-37250/KHK2804 tolerability and safety data from three subjects enrolled in a cohort, enrollment at the next dose level or additional subjects into the ongoing cohort will occur based upon the number subjects with DLT at a given dose level. Dose depends on subject's body weight. Part 1 includes intervention of CEP-37250/KHK2804. Part 2 will receive CEP-37250/KHK2804 at a dose to be determined following completion of Part 1.; Other Names: KHK2804
Experimental: Part 2; Subjects with colorectal or pancreatic cancer Part 2 which includes intervention of CEP-37250/KHK2804	Drug: CEP-37250/KHK2804; Part 1 is based on the CEP-37250/KHK2804 tolerability and safety data from three subjects enrolled in a cohort, enrollment at the next dose level or additional subjects into the ongoing cohort will occur based upon the number subjects with DLT at a given dose level. Dose depends on subject's body weight. Part 1 includes intervention of CEP-37250/KHK2804. Part 2 will receive CEP-37250/KHK2804 at a dose to be determined following completion of Part 1.; Other Names: KHK2804

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event collection and assessment will be done for all 74 potentially treated subjects.	The safety of CEP-37250/KHK2804 will be determined by reported adverse events (AEs), changes in the physical examinations, vital laboratory evaluations, and treatment discontinuations due to toxicity.	at least 30 days or up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess PK parameters which include: area under the plasma concentration versus time curve (AUC), peak plasma concentration (Cmax), t 1/2 and CL of CEP-37250/KHK2804.	Participating subjects will have serial blood samples taken to determine the PK profile of study drug.	at least 30 days or up to 12 weeks
To screen for the development of antibodies against CEP-37250/KHK2804 (immunogenicity)	Subjects will have serial blood samples to check for the developments of anti-CEP-37250/KHK2804 antibodies.	at least 30 days or up to 12 weeks
To evaluate preliminary efficacy (overall response (Objective response rate(ORR; Complete Response(CR)+Partial Response(PR) and clinical benefit rate(CR+PR+stable disease(SD)).	Tumor measurements and disease response assessments will be performed on all participating subjects.	up to 30 days or up to 12 weeks

Collaborators and Investigators

• Sponsor: Kyowa Hakko Kirin Pharma, Inc.
• Collaborators: Teva Pharma
• Investigators: Study Director: Michael Tirgan, MD, Kyowa Hakko Kirin Pharma, Inc.

Publications and helpful links

General Publications

• Mita MM, Nemunaitis J, Grilley-Olson J, El-Rayes B, Bekaii-Saab T, Harvey RD, Marshall J, Zhang X, Strout V. Phase 1 Study of CEP-37250/KHK2804, a Tumor-specific Anti-glycoconjugate Monoclonal Antibody, in Patients with Advanced Solid Tumors. Target Oncol. 2016 Dec;11(6):807-814. doi: 10.1007/s11523-016-0449-2.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 5, 2011
• First Posted (Estimate): October 6, 2011

Study Record Updates

• Last Update Posted (Estimate): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Monoclonal antibody (Mab); Antibody dependent cellular cytotoxicity (ADCC); Complement-dependent toxicity (CDC); Non-fucosylated immunoglobulin G
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: CEP-37250/KHK2804-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No