Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors

NCT ID: NCT01966445

Last Updated: 2019-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-26
• Study Completion Date: 2017-09-18

Brief Summary

Human Epidermal Growth Factor Receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody targeting HER3, is a new agent for subjects whose tumors express HER3. This study is a phase I, first time in human, open-label, dose escalation study. The purpose of this study is to investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849330 in subjects with advanced HER3-positive solid tumors. The study will be conducted in two parts. Part 1 (Dose-Escalation Phase) will include dose escalation and PK/PD cohorts to evaluate safety, PK, and PD to guide selection of dose regimen(s) for Part 2. In Part 2 (Expansion Cohorts), up to 3 cohorts will be enrolled at the dose regimen(s) selected based on Part 1 data, to evaluate safety in a larger cohort of subjects at the recommended dose regimen and also to evaluate preliminary evidence of clinical benefit.

Conditions

Cancer; Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GSK2849330 Part 1

1 hour infusion administered intravenously at intervals of one week or more (escalating doses).

Group Type: EXPERIMENTAL

GSK2849330

Intervention Type: BIOLOGICAL

Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion

GSK2849330 Part 2

Intravenous infusion administered at the dose and schedule established in Part 1

Group Type: EXPERIMENTAL

GSK2849330

Intervention Type: BIOLOGICAL

Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion

Interventions

GSK2849330

Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Males and females >=18 years of age (at the time consent is obtained).
• Written informed consent provided.
• Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• Sufficient archival tumor specimen is available for HER3 immunohistochemistry (IHC) analysis, or subject is willing to undergo a fresh tumor biopsy for HER3 IHC analysis.
• Histologically or cytologically confirmed diagnosis of one of the following solid tumor malignancies for which no standard therapeutic alternatives exist: bladder cancer, breast cancer, castrate-resistant prostate cancer, cervical cancer, colorectal cancer (CRC), gastric cancer, hepatocellular carcinoma (HCC), melanoma, non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, squamous cancers of the head and neck region (including parotid and nasopharynx).

Exclusion Criteria

• Subjects with leptomeningeal or brain metastases or spinal cord compression.
• Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
• Concurrent medical condition that would jeopardize compliance.
• Receiving chronic immunosuppressive therapies (includes daily steroid doses in excess of 20 milligrams [mg]/day of prednisone).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Locations

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Heidelberg, Victoria, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Groningen, , Netherlands

GSK Investigational Site

Groningen, , Netherlands

GSK Investigational Site

Nijmegen, , Netherlands

GSK Investigational Site

Nijmegen, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

Countries

United States; Australia; Netherlands

References

Drilon A, Somwar R, Mangatt BP, Edgren H, Desmeules P, Ruusulehto A, Smith RS, Delasos L, Vojnic M, Plodkowski AJ, Sabari J, Ng K, Montecalvo J, Chang J, Tai H, Lockwood WW, Martinez V, Riely GJ, Rudin CM, Kris MG, Arcila ME, Matheny C, Benayed R, Rekhtman N, Ladanyi M, Ganji G. Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers. Cancer Discov. 2018 Jun;8(6):686-695. doi: 10.1158/2159-8290.CD-17-1004. Epub 2018 Apr 2.

Reference Type: DERIVED

PMID: 29610121 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-001699-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

117158

Identifier Type: -

Identifier Source: org_study_id