Phase 1
N=20
Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors
Cancer · Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT01966445 ↗Enrolled (actual)
20
Serious AEs
20.7%
Results posted
Jul 2019
Primary outcome: Primary: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Parts 1 and 2 — 1; 3; 2; 5 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK2849330 (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Parts 1 and 2 |
1; 3; 2; 5; 4; 14 | — |
| PRIMARY Number of Participants With Dose-limiting Toxicities (DLTs)-Parts 1 and 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Parts 1 and 2 |
1; 1; 0; 3; 3; 6 | — |
| PRIMARY Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Parts 1 and 2 |
0; 0; 1; 0; 0; 0 | — |
| PRIMARY Number of Participants With Grade Change From Baseline in Hematology Data-Parts 1 and 2 |
0; 1; 0; 0; 3; 7 | — |
| PRIMARY Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Parts 1 and 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Urinalysis Data With Respect to Normal Range-Parts 1 and 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Vital Signs-Parts 1 and 2 |
1; 1; 0; 2; 0; 4 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Parts 1 and 2 |
1; 3; 1; 4; 3; 4 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of GSK2849330-Part 1 |
29790.0; 62495.2; 83845.0; 233997.8; 639127.3; 778470.6 | — |
| SECONDARY Cmax of GSK2849330-Part 2 |
— | — |
| SECONDARY Time of Occurrence of Cmax (Tmax) for GSK2849330-Part 1 |
2.070; 2.130; 88.035; 2.280; 3.280; 2.100 | — |
| SECONDARY Tmax for GSK2849330-Part 2 |
— | — |
| SECONDARY Area Under the Concentration Time Curve (AUC) to a Fixed Nominal Time (AUC[0 to 168]) and AUC(0 to 336) for GSK2849330-Part 1 |
1962762.0; 5787797.8; 618552.6; 18185733.6; 54346531.5; 54388333.7 | — |
| SECONDARY AUC(0 to 168) and AUC(0 to 336) for GSK2849330-Part 2 |
— | — |
| SECONDARY Serum HER3 From Tumor Tissue-Parts 1 and 2 |
13.65; 17.11; 16.66; 14.42; 13.67; 11.08 | — |
| SECONDARY Overall Response Rate (ORR)-Parts 1 and 2 |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Antibodies to GSK2849330 in Serum |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Percentage of Cluster of Differentiation (CD) Marker |
99.80; 99.83; 99.90; 99.76; 99.93; 101.57 | — |
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.
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).
Data sourced from ClinicalTrials.gov (NCT01966445). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.