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

NCT01447732 | Completed Phase 1

• 1 other identifier: CEP-37250/KHK2804-001
• Study Type: interventional
• Target: 71
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Solid Tumour; Adenocarcinoma of the Colorectal; Adenocarcinoma of the Pancreas

Keywords

Monoclonal antibody (Mab); Antibody dependent cellular cytotoxicity (ADCC); Complement-dependent toxicity (CDC); Non-fucosylated immunoglobulin G

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

  at least 30 days or up to 12 weeks

• To screen for the development of antibodies against CEP-37250/KHK2804 (immunogenicity)

  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)).

  up to 30 days or up to 12 weeks

Study Arms (2)

Part 1

EXPERIMENTAL

Dose escalation in subjects with advanced solid tumors with Part 1 which includes intervention of CEP-37250/KHK2804

Drug: CEP-37250/KHK2804

Part 2

EXPERIMENTAL

Subjects with colorectal or pancreatic cancer Part 2 which includes intervention of CEP-37250/KHK2804

Drug: CEP-37250/KHK2804

Interventions

CEP-37250/KHK2804 DRUG

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.

Also known as: KHK2804

Part 1; Part 2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Parts 1 and 2:
• 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;
• 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;
• 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;
• Major surgery within 4 weeks prior to the first dose;
• 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.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Teva Pharma: collaborator
• Kyowa Hakko Kirin Pharma, Inc.: collaborator

Related Publications (1)

• 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.

  PMID: 27457707 DERIVED

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Michael Tirgan, MD

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 6, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 29, 2024

Record last verified: 2024-04