Solid Tumors Clinical Trial
Official title:
A Multicenter, Open Label, Phase I Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous SAIT301 in Subjects With Advanced c-MET Positive (+) Solid Tumors Followed by Expansion in Selected Tumor Types
Verified date | January 2018 |
Source | Samsung Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Mesenchymal epithelial transition factor (c-MET) is a receptor tyrosine kinase that, when
engaged by its ligand hepatocyte growth factor (HGF), has been implicated in various cellular
process including development as well as oncogenesis.
SAIT301 is a novel humanized monoclonal antibody targeting the alpha chain of extracellular
domain of c-MET. Binding of SAIT301 to c-MET blocks HGF binding and inhibits HGF-mediated
signaling. Furthermore, SAIT301 also induces efficient c-MET internalization from the cell
surface and subsequent degradation, resulting in inhibition of growth of the c-MET addicted
cancer cells.
The sponsor decided to enroll subjects with tumors that express c-MET (by
immunohistochemistry [IHC]) for this study, as the subjects with no c-MET expression are
unlikely to benefit from SAIT301 treatment.
Stage 1 of this Phase I study is designed to evaluate the safety, tolerability,
pharmacokinetic (PK) profile, and anti-tumor activity of SAIT301 administered as a single IV
infusion in 21 day cycles, for up to 4 cycles. Subjects without evidence of tumor progression
after 4 cycles will be eligible to continue on SAIT301 treatment if there is no evidence of
tumor progression for a further 4 cycles (Cycles 5 to 8). Biomarkers related to SAIT301
and/or tumor response will also be evaluated.Stage 2 will further evaluate the safety and PK
profile of SAIT301 in select types of cancers. Dosing frequency may be adjusted based on the
PK profile obtained during Stage 1.
Status | Completed |
Enrollment | 16 |
Est. completion date | June 20, 2017 |
Est. primary completion date | March 15, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Aged 18 years or older. 2. Have a histologically or cytologically confirmed advanced solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or the subject is not a candidate for standard therapy. 3. Tumor positive for c-MET expression as determined by IHC. Results should be available before the subject can proceed in the study. 4. Adequate tumor biopsy material should be available for IHC and fluorescence in situ hybridization (FISH) of c-MET and biomarker analysis at the time of enrollment (formalin-fixed, paraffin-embedded tumor block or 20 fresh cut unstained slides). 5. At least 28 days must have elapsed since the subject's prior systemic therapy, radiotherapy, or any major surgery (excluding diagnostic biopsy or venous access device placement). Surgery requiring local/epidural anesthesia must be completed at least 72 hours before the first administration of SAIT301. For concomitant medications with a known half-life of less than 36 hours (e.g., tyrosine kinase inhibitors), the duration of time since prior therapy can be reduced to 14 days provided any drug-related toxicities have resolved to Grade 1 or better. Hormonal therapy for prostate or breast cancer are allowed during the study. 6. For dose levels 1 to 3, subjects must, at a minimum, have evaluable disease according to RECIST 1.1 guidelines. For dose levels above level 3, subjects must have measureable disease (=1 cm by spiral computerized tomography [CT] or =2 cm by standard CT). 7. An ECOG performance status of <2. 8. Life expectancy of >12 weeks, as judged by the investigator. 9. Female subjects must not be pregnant or breastfeeding, or at risk to become pregnant during the study. Fertile male and female subjects must agree to use an effective barrier method of birth control to avoid pregnancy from the time of providing informed consent until 90 days after the last administration of SAIT301. 10. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of SAIT301. For the purpose of this study, female subjects of childbearing potential are defined as all female subjects after puberty unless they are postmenopausal for at least 1 year, or are surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation). 11. Adequate organ function as indicated by the laboratory test results obtained within 7 days prior to the first administration of SAIT301: Hematologic: Absolute neutrophil count =1.5 x 109/L, platelet count =100 x 109/L, and hemoglobin =9.0 g/dL. Liver function: Serum bilirubin <2.0 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 x upper limit of normal (ULN) without liver involvement, or <5 x ULN with liver involvement. Renal: serum creatinine =1.5 mg/dL. 12. Willing and able to provide written informed consent and to comply with the protocol, visit schedule, and requirements. Exclusion Criteria: Subjects will not be entered in the study for any of the following reasons: 1. Received previous treatment with SAIT301 or a previous drug with c-MET inhibitory activity. 2. Received any chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational, within 28 days of the first administration of SAIT301 in this study. 3. History of prior allergic reactions to protein therapeutics. 4. Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant. 5. Symptomatic or untreated central nervous system metastases. 6. Not recovered from acute toxicity of any therapy received prior to enrollment. 7. Received systemic treatment for bacterial infection within 7 days of screening. 8. Positive test results for human immunodeficiency virus (HIV), hepatitis B (core immunoglobulin M antibody and/or surface antigen), or hepatitis C at screening. 9. Any other serious medical condition which in the investigator's opinion would preclude safe participation in the study. 10. Likely to be non-compliant or uncooperative during the study, as judged by the investigator. |
Country | Name | City | State |
---|---|---|---|
Korea, Republic of | Samsung Medical Center | Seoul |
Lead Sponsor | Collaborator |
---|---|
Young Suk Park |
Korea, Republic of,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events (AEs) of at least Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 severity, and discontinuations due to AEs. | Adverse events will be evaluated and categorized in accordance with the CTCAE, version 4.03. | Up to 25 weeks for each subject | |
Primary | The maximum tolerated dose (MTD) of SAIT301 and the dose level of SAIT301 where dose limiting toxicity (DLT) is observed in subjects with advanced solid tumors | The frequency of DLTs as part of the MTD determination process. | Up to 25 weeks for each subject | |
Primary | A recommended Phase II dose (RP2D) as an alternative to establishing the MTD. | RP2D determination as an alternative to establishing the MTD | Up to 25 weeks for each subject | |
Secondary | The pharmacokinetic (PK) profile of SAIT301 | Free SAIT301 for Cycle 1 and Cycle 4 over dosing observation period of 0 to 21 days: maximum observed serum concentration (Cmax), time to maximum serum concentration (tmax), area under the serum concentration-time curve from zero to the last quantifiable concentration (AUC0-t), area under the concentration-time curve over the dosing interval (AUC0-tau). Free SAIT301 for Cycle 1, if half-life can be estimated with acceptable accuracy and/or for Cycle 4 if data collected in Cycle 4 are representative of steady state: area under the serum concentration-time curve from zero extrapolated to infinity (AUC0-inf), elimination rate constant (?z), elimination half-life (t1/2), apparent clearance from serum (CL), and volume of distribution at steady-state (VSS). |
Up to 25 weeks for each subject | |
Secondary | Objective tumor response for target lesions based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, as assessed by repeat computerized tomography (CT) or magnetic resonance imaging (MRI). | Up to 25 weeks for each subject | ||
Secondary | To assess the preliminary anti-tumor activity of SAIT301 when administered as a single agent in this subject population | Development of anti-SAIT301 binding antibodies and neutralizing antibodies | Up to 25 weeks for each subject |
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