A Phase 1 Study of KBP-5209 in Patients With Advanced Solid Tumors

The purpose of this study is to determine the maximum tolerated dose of KBP-5209 as a single agent when given orally to adult patients with advanced solid tumors that have progressed despite standard therapy, or where there is no standard therapy.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: KBP-5209

Detailed Description

This is a Phase 1, open-label, multicenter study of KBP-5209 administered orally once daily (QD) in 28-day treatment cycles to adult patients with advanced solid tumors which have progressed despite standard therapy or for which no standard therapy exists. This study is designed to determine the MTD or RP2D and to characterize the safety, tolerability, and PK profile of KBP-5209.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older;
• Patients with histologically or cytologically confirmed, advanced solid tumors which have progressed despite standard therapy or for whom no standard therapy exists.
• Patients must have at least one measurable or non-measurable lesion (dose escalation only) as defined by RECIST v1.1
• Eastern Cooperative Oncology Group performance score 0 to 2;

Exclusion Criteria:

• Patients with symptomatic CNS metastases;
• Patients who have a known history of hepatitis C or chronic active hepatitis B or a known diagnosis of HIV
• Any significant ophthalmologic abnormality
• Patients who have any severe and/or uncontrolled medical conditions
• Significant gastrointestinal abnormalities,
• Patients who have impaired cardiac function or clinically significant cardiac diseases,
• Chemotherapy, biologic therapy, immunotherapy, radiotherapy or investigational agents within 5 half-lives or within 4 weeks (whichever is longer) prior to administration of the first dose of study drug on Day 1 or have not recovered from the side effects of such therapy;
• Treatment with third generation EGFR inhibitors
• Major surgery/surgical therapy for any cause within 4 weeks of Screening;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KBP-5209; Dose escalation for KBP-5209 will initially follow a modified accelerated titration design with a starting dose of 20 mg QD. Early dose escalation will proceed with one-patient cohorts and 100% dose increments (ie, dose doubling) until a patient experiences a DLT, at which point the cohorts will move to a 3+3 design. Treatment will continue until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons. A cycle is defined as continuous treatment for 28 days.

Drug: KBP-5209; Single oral dose beginning at 20 mg with daily dosing for 28 day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Outcome Measure: safety and tolerability, based on the rate of dose-limiting toxicities, toxicity grade, and reversibility of toxicity.	2 Years

Secondary Outcome Measures

Outcome Measure	Time Frame
Dose-dependency of toxicity based on: dose limiting toxicities; frequency, type, grade, and seriousness, and causality of treatment-emergent adverse events, and laboratory assessments.	While undergoing study treatment and up to 30 days after the last dose of KBP-5209

Collaborators and Investigators

• Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.
• Collaborators: Covance; XuanZhu Pharma Co., Ltd.

Publications and helpful links

General Publications

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
• Simon R, Freidlin B, Rubinstein L, Arbuck SG, Collins J, Christian MC. Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst. 1997 Aug 6;89(15):1138-47. doi: 10.1093/jnci/89.15.1138.
• Gibaldi M, Perrier D. Pharmacokinetics. 2nd edition. New York, NY: Marcel Dekker, Inc.; 1982.
• ICH E3: Guideline for Industry: Structure and Content of Clinical Study Reports. 1996.
• Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, Chaudhuri S, Pujara K, Guillory J, Edgar KA, Janakiraman V, Scholz RP, Bowman KK, Lorenzo M, Li H, Wu J, Yuan W, Peters BA, Kan Z, Stinson J, Mak M, Modrusan Z, Eigenbrot C, Firestein R, Stern HM, Rajalingam K, Schaefer G, Merchant MA, Sliwkowski MX, de Sauvage FJ, Seshagiri S. Oncogenic ERBB3 mutations in human cancers. Cancer Cell. 2013 May 13;23(5):603-17. doi: 10.1016/j.ccr.2013.04.012. Erratum In: Cancer Cell. 2014 Apr 14;25(4):543-4.
• Li M, Liu F, Zhang F, Zhou W, Jiang X, Yang Y, Qu K, Wang Y, Ma Q, Wang T, Bai L, Wang Z, Song X, Zhu Y, Yuan R, Gao Y, Liu Y, Jin Y, Li H, Xiang S, Ye Y, Zhang Y, Jiang L, Hu Y, Hao Y, Lu W, Chen S, Gu J, Zhou J, Gong W, Zhang Y, Wang X, Liu X, Liu C, Liu H, Liu Y, Liu Y. Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis. Gut. 2019 Jun;68(6):1024-1033. doi: 10.1136/gutjnl-2018-316039. Epub 2018 Jun 28.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2015
• Primary Completion (Actual): November 26, 2019
• Study Completion (Actual): November 26, 2019

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: May 8, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; HER2; Gastric Cancer; EGFR; Colorectal Cancer; Advanced Solid Tumors; HER3; Metastatic Non Small Cell Lung Cancer; HER4; ALK mutations; irreversible tyrosine kinase inhibitor
• Other Study ID Numbers: 5209-CPK-1001