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

NCT02296879 | Completed Phase 1 DMC

• 1 other identifier: 2014-09-077
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (3)

• The pharmacokinetic (PK) profile of SAIT301

  Up to 25 weeks for each subject

• 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

• To assess the preliminary anti-tumor activity of SAIT301 when administered as a single agent in this subject population

  Up to 25 weeks for each subject

Study Arms (1)

SAIT301

EXPERIMENTAL

For Stage 1, subjects will be sequentially assigned to 1 of approximately 8 cohorts comprised of 3 to 6 subjects each. SAIT301 will be administered according to a modified Fibonacci sequence and following a 3 + 3 design. For Stage 2, the MTD or (RP2D) determined in the Stage 1 will be administered to additional subjects with selected diagnoses, 15 subjects per selected diagnosis. After completion of Stage 1 the SRC may elect to increase the interval between doses (i.e., increase cycle length to 28 days) based on the emerging PK data from the lower SAIT301 dose levels.

Genetic: SAIT301

Interventions

SAIT301 GENETIC

The treatment period will consist of 21-day cycles. On Day 1 of each cycle, SAIT301 will be administered as an intravenous (IV) infusion.

SAIT301

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older.
• 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.
• Tumor positive for c-MET expression as determined by IHC. Results should be available before the subject can proceed in the study.
• 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).
• 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.
• 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).
• An ECOG performance status of \<2.
• Life expectancy of \>12 weeks, as judged by the investigator.
• 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.
• 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).
• 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.
• Willing and able to provide written informed consent and to comply with the protocol, visit schedule, and requirements.

You may not qualify if:

• Subjects will not be entered in the study for any of the following reasons:
• Received previous treatment with SAIT301 or a previous drug with c-MET inhibitory activity.
• 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.
• History of prior allergic reactions to protein therapeutics.
• Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant.
• Symptomatic or untreated central nervous system metastases.
• Not recovered from acute toxicity of any therapy received prior to enrollment.
• Received systemic treatment for bacterial infection within 7 days of screening.
• Positive test results for human immunodeficiency virus (HIV), hepatitis B (core immunoglobulin M antibody and/or surface antigen), or hepatitis C at screening.
• Any other serious medical condition which in the investigator's opinion would preclude safe participation in the study.
• Likely to be non-compliant or uncooperative during the study, as judged by the investigator.

Sponsors & Collaborators

• Young Suk Park: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

MeSH Terms

Interventions

SAIT301

Study Officials

• Park Yong Suk, MD,Ph.D.

  Samsung Medical Center,Seoul,Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Samsung Medical Center

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 20, 2014
• Study Start: January 20, 2015
• Primary Completion: March 15, 2017
• Study Completion: June 20, 2017
• Last Updated: January 17, 2018

Record last verified: 2018-01

Locations

KR (1)