A Phase I Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of MRX-2843 in Adult Subjects With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors

Meryx, Inc.2 sites in 1 country42 target enrollmentMay 22, 2018

ConditionsAdvanced Cancer Metastatic Cancer Neoplasms Neoplasm Metastasis Neoplastic Processes Pathologic Processes

InterventionsMRX-2843

DrugsMRX-2843

Overview

Phase: Phase 1
Intervention: MRX-2843
Conditions: Advanced Cancer
Sponsor: Meryx, Inc.
Enrollment: 42
Locations: 2
Primary Endpoint: Percentage of subjects with Dose Limiting Toxicities (DLTs)
Status: Completed
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This first-in-human open-label, dose escalation study is designed to evaluate the safety, tolerability, and PK of MRX-2843 in subjects with relapsed/refractory advanced and/or metastatic solid tumors.

Registry

clinicaltrials.gov

Start Date

May 22, 2018

End Date

December 31, 2025

Last Updated

3 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Meryx, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female at least 18 years of age.
•Histologically or cytologically confirmed, measurable (defined as those that could be accurately measured in a least 1 dimension with a longest diameter ≥20 mm using conventional techniques or ≥10 mm with spiral computed tomography scan) or evaluable solid malignancy (with the exception of primary central nervous system \[CNS\] tumors) per RECIST 1.
•Scans performed within 1 month of starting study drug will be accepted.
•Received at least one systemic therapy for advanced disease, with no further approved treatment options that provide proven clinical benefit.
•Eastern Cooperative Oncology Group (ECOG) performance status ≤
•Females of childbearing potential who are sexually active with a nonsterilized male partner agree to use 2 methods of effective contraception from screening, and agree to continue using such precautions for 90 days after the final dose of study drug; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
•Nonsterilized males who are sexually active with a female of childbearing potential must agree to use an acceptable method of effective contraception from Day 1 and for 90 days after the final dose of study drug.
•Female subjects of childbearing potential must be nonpregnant, nonlactating, and have a negative pregnancy test result at Screening and Day 1 of Cycles 1-
•Able to provide written, informed consent before initiation of any study related procedures, and is able, in the opinion of the Investigator, to comply with all the requirements of the study.
•Able to swallow oral medication.

Exclusion Criteria

•Subject has an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically significant and would preclude study participation.
•Subject has QT interval corrected (QTc) \>480 ms (both males and females) at Screening (repeat values may be obtained during the period between Screening and admission to the study site).
•Subject has any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug, or any other condition that may place the subject at risk for such interference (for example, short bowel syndrome or inflammatory bowel disease).
•Subject has a history of Type 1 Diabetes (T1D) or is considered at high risk for T1D, where high risk is defined as
•Subject has 1 first-degree relative (FDR; defined as parents, offspring or siblings) with T1D AND A1C value \> 6.5% or
•Subject has 2+FDR with T1D
•Subject has uncontrolled hypertension, defined as a blood pressure reading \>160/100 mmHg, despite maximum antihypertensive therapy.
•Subject has received:
•Radionuclide treatment within 6 weeks of the first dose of study drug in this study
•Local palliative radiation therapy (XRT) (small port) ≤2 weeks before first dose of study drug

Arms & Interventions

MRX-2843

MRX-2843: Dose Escalation Successive dose escalation cohorts to determine MTD

Intervention: MRX-2843

Outcomes

Primary Outcomes

Percentage of subjects with Dose Limiting Toxicities (DLTs)

Time Frame: Baseline to the end of Cycle 1 (up to 28 days)

Percentage of subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5

Time Frame: Baseline up to 14 days after last dose of study treatment (up to approximately 12 months)

Secondary Outcomes

CL/F: apparent total body clearance(Day 1 and Day 16 of Cycle 1)
Determine Maximum Tolerated Dose (MTD) in mg of MRX-2843(Baseline to end of Cycle 1 (up to 28 days))
AUC0-t: area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (t)(Day 1 and Day 16 of Cycle 1)
AUC0-inf: area under the concentration-time curve from time 0 to infinity(Day 1 and Day 16 of Cycle 1)
AUC0-τ: area under the concentration-time curve from time 0 to tau, where tau is the dosing interval(Day 1 and Day 16 of Cycle 1)
Cmax: maximum observed plasma concentration(Day 1 and Day 16 of Cycle 1)
Tmax: time to reach maximum observed plasma concentration(Day 1 and Day 16 of Cycle 1)
λz: terminal phase elimination rate constant(Day 1 and Day 16 of Cycle 1)
t1/2: apparent terminal elimination half-life(Day 1 and Day 16 of Cycle 1)
Vz/F: apparent volume of distribution of the terminal phase(Day 1 and Day 16 of Cycle 1)