A Phase 1 study of anti-HER3 monoclonal antibody GSK2849330, in subjects with advanced HER3-positive solid tumors.
- Conditions
- MedDRA version: 17.1Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Subjects with advanced HER3-positive solid tumorsMedDRA version: 17.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: LLTClassification code 10033575Term: Pancreas cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2013-001699-39-NL
- Lead Sponsor
- GlaxoSmithKline Research Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 154
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
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 <50%
-A QT interval corrected for HR (QTc) = 480 msec (=500 msec for subjects
with bundle branch block)
- History or evidence of current clinically significant uncontrolled
arrhythmias.
Exception: Subjects with controlled atrial fibrillation for >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).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method