Subjects with advanced HER3-positive solid tumors MedDRA version: 17.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.1 Level: LLT Classification code 10033575 Term: Pancreas cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.1 Level: PT Classification code 10060862 Term: Prostate cancer Sys
Conditions
Interventions
Product Name: GSK2849330
Product Code: GSK2849330
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: GSK2849330
Other descriptive name: GSK284933
Sponsors
GlaxoSmithKline Research Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Inclusion criteria please view the following sections within the protocol. For Pre-screening Inclusion Criteria for Part 1 & 2 see protocol section 5.2.1 -5.2.2. P 60-61. For Screening Inclusion Criteria for Parts 1 and 2 see below 1. Males and females =18 years of age (at the time consent is obtained). 2. Written informed consent provided. 3. For subjects enrolled in Part 1:subjects must have tumors with documented HER3 expression (2+ or 3+) on the cell surface of the invasive component of the tumor (either on archival tissue or fresh tumor biopsy) using an analytically validated IHC assay by central laboratory (see protocol section 7.6.1.1 for details). Subjects enrolled in Part 2 must meet inclusion criterion 9 listed below. 4. ECOG performance status of 0 or 1 (see protocol Appendix 3). 5. Adequate baseline organ function defined by: Please see table for further information. 6. If the subject is female, she must be of non-childbearing potential, i.e., have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in protocol Section 11.1.1, from the time of the first dose of study treatment until 45 days or 5 half-lives (whichever is longer) after the last dose of study treatment. 7. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in Section 11.1.2 from the time of the first dose of study treatment until 45 days or 5 half-lives (whichever is longer) after the last dose of study treatment to allow for clearance of GSK2849330 in seminal fluid. 8. Subjects enrolled as part of the PK/PD cohort (Part 1) must agree to undergo preand on-treatment tumor biopsies. For Inclusion Criteria for Part 2 ONLY section 5.2.4. of the protocol As listed above for Part 1, with the exception of criterion 3 which should be replaced with the following criterion 9 and the addition of criteria 10 and 11. 9. For Group 1: subjects with previously treated, unresectable stage III or IV melanoma with documented HER3 expression (3+) on the cell surface of the invasive component of the tumor (either on archival tumor or fresh tumor biopsy) using an analytically validated IHC assay by central laboratory. - Subjects must have no more than 3 prior lines of systemic regimens and have disease progression on or after last prior treatment (based on RECIST v1.1). - Subjects with BRAF V600 mutations who already received or were intolerant of prior BRAF inhibitor therapy may be included. BRAF V600 inhibitor-naïve subjects will be eligible if a BRAF inhibitor is not available to them commercially or via a clinical trial. - Subjects may be included if they had prior immune therapy, were intolerant of prior immune therapy, or if such therapy is not available to them commercially or via a clinical trial. For Group 2: Subjects with previously treated, unresectable stage III or IV gastric or gastroesophageal junction (GEJ) adenocarcinoma with documented HER3 expression (3+) on the cell surface of the invasive component of the tumor (either on archival tumor or fresh tumor biopsy) using an analytically validated IHC assay by central laboratory. - Subjects must have no more than 3 prior lines of systemic regimens and have disease progression
Exclusion criteria
Exclusion criteria: 1. Subjects with leptomeningeal or brain metastases or spinal cord compression. - Subjects with untreated brain or meningeal metastases are not eligible (computed tomography [CT] scans are not required to rule this out unless there is a clinical suspicion of central nervous system [CNS] disease). - Subjects with treated and radiologic or clinical evidence of stable brain metastases (confirmed by 2 scans at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain lesion are eligible providing that they are asymptomatic and do not require corticosteroids. Subjects are not permitted to receive enzyme inducing anti-epileptic drugs. 2. Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable). 3. Use of an investigational anti-cancer drug within 28 days (or 5 half -lives, whichever is longer) preceding the first dose of GSK2849330 OR chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C) OR any major surgery, radiotherapy, immunotherapy or any other anti-cancer therapy within the last 4 weeks, except as noted above. 4. Unresolved toxicity greater than NCI-CTCAE, version 4.0 [NCI, 2009] Grade 1from previous anti-cancer therapy except alopecia and stable anemia (i.e.,untransfused Hb =9.0 g/dL without the need for supportive transfusion within 2 weeks of screening) at the time of treatment allocation. 5. Known or suspected hypersensitivity reaction to prior biologic therapy (e.g., therapeutic monoclonal antibody) that in the opinion of the investigator is a contraindication to their participation in the study. 6. Current use of a prohibited medication or requires any of these medications during treatment (protocol Section 10.2). 7. History or evidence of significant cardiovascular risk including any of the following: - LVEF 30 days prior to enrollment are eligible. - History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment. - History or evidence of current = Class II congestive heart failure as defined by New York Heart Association (NYHA). 8. Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed). 9. Evidence of another active malignancy (excludes non-melanoma skin cancer). Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above. 10. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 11. Concurrent medical condition that in the investigator’s opinion would jeopardize compliance with the protocol. 12. Lactating female. 13. Receiving chronic immunosuppressive therapies (includes daily steroid doses in excess of 20 mg/day of prednisone).
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o PK parameter values for GSK2849330. o Total and phospho-HER3 from tumor tissue. o Safety, tolerability, PK, and available PD data. o Antibodies to GSK2849330 assessed in serum. o Overall response rate (ORR), tumor markers, and other measures of clinical benefit. ;Timepoint(s) of evaluation of this end point: o PK sampling every week in the first 12 weeks then every 12 weeks. In Part 2: PK sampling every 2 weeks in the first 12 weeks then every 12 weeks. o Tumor tissue prestudy, D15 and discontinuation. | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of GSK2849330 in subjects with advanced HER3- positive solid tumors.;Secondary Objective: To characterize the PK of GSK2849330 following IV administration. To evaluate preliminary evidence of target engagement and PD effects of GSK2849330 To determine the recommended dose regimen(s) of GSK2849330 for further exploration in Part 2. To evaluate the immunogenicity of GSK2849330 following IV administration. To evaluate preliminary evidence of clinical benefit in Part 2;Primary end point(s): Primary endpoints: AEs, serious adverse events (SAEs), DLTs, and changes in laboratory values, electrocardiograms (ECGs), and vital signs;Timepoint(s) of evaluation of this end point: o AEs and SAEs on a continuous basis o DLTs within first 28 days o Chemistry and Hematology is at every infusion o Urinalysis every 4 weeks o ECG is at every 2weeks in the first months then every 4 weeks. o Vital signs at every infusion | — |
Countries
Australia, Netherlands, United States
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed