A Phase 1 Study of NOV1601(CHC2014) in Adult Subjects With Solid Organ Malignancies

A Phase 1, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of NOV1601(CHC2014) in Adult Subjects With Solid Organ Malignancies

This study is a first-in-human (FIH) study which is required to understand the PK characteristics, MTD, and safety profile of NOV1601(CHC2014) in subjects with solid organ malignancies.

Study Overview

• Status: Completed
• Conditions: Solid Tumor, Adult; Phase 1
• Intervention / Treatment: Drug: NOV1601(CHC2014)

Detailed Description

This is the first-in-human, Phase 1, open-label, multicenter, dose-escalation study to investigate the safety, tolerability, PK, and clinical activity of NOV1601(CHC2014) in subjects with solid organ malignancies. The primary goal of the study is to determine the RP2D of NOV1601(CHC2014) in adult subjects with solid organ malignancies.

Dose escalation will follow a 3+3 design and will be based on prior cohort review. There will be 2 branches of the dosing schedule, once a day(QD) and twice daily(BID).

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Gyeonggi-do
    • Goyang, Gyeonggi-do, Korea, Republic of
      • National Cancer Center
    • Seongnam, Gyeonggi-do, Korea, Republic of
      • CHA Bundang Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria(partial):

• Pathological confirmation of malignancy and evidence of metastatic or surgically unresectable disease
• At least one evaluable or measurable lesion should be present and identified according to Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1 or Response Assessment in Neuro-Oncology(RANO)
• Relapse after or refractory to systemic drug therapy to malignancy, at least one regimen of cytotoxic chemotherapy, kinase inhibitors including tyrosine kinase inhibitors or immunotherapy which is considered as standard of care if there is no standard regimen recommended, then no experience of systemic drug therapy is acceptable

• Patients with primary central nervous system(CNS) tumors or metastasis, if they have been neurologically stable

  • Symptoms should be under control by stable dose of glucocorticoids and analgesic drugs for symptom control at least 2 weeks prior to starting the treatment
  • Stable dose of glucocorticoids and analgesic drugs for symptom control should be maintained throughout the study
  • Subjects should be off from radiotherapy for at least 14 days prior to the start of study treatment(C1D1) without symptom aggravation

Exclusion Criteria(partial):

• Prior high-dose chemotherapy requiring hematopoietic stem cell transplantation
• History or evidence of suspicious leptomeningeal disease
• Previous surgery of gastrectomy, gastrostomy or any medical condition which interferes with oral ingestion of capsule
• Indwelling percutaneous drainage of bile and chest tube
• Evidence of or suspicious symptomatic spinal cord compression, unless appropriately treated and neurologically stable off glucocorticoid for at least 2 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NOV1601(CHC2014); a highly selective pan-TRK(tropomyosin receptor kinase) inhibitor targeting tropomyosin receptor kinase A(TRKA), tropomyosin receptor kinase B(TRKB), and tropomyosin receptor kinase C(TRKC)	Drug: NOV1601(CHC2014); a highly selective pan-TRK(tropomyosin receptor kinase) inhibitor targeting tropomyosin receptor kinase A (TRKA), tropomyosin receptor kinase B(TRKB), and tropomyosin receptor kinase C(TRKC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the recommended Phase 2 dose(RP2D) or the maximum tolerated dose(MTD) of NOV1601	MTD will be the RP2D, based on the pharmacokinetic(PK) profiles and safety profiles as assessed by the Safety Monitoring Committee (SMC).	Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events(TEAE) and serious adverse events(SAE)	Each adverse event will be coded using the Medical Dictionary for Regulatory Activities(version 20.0) classification system. The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.	Maximum 2 years

Collaborators and Investigators

• Sponsor: Handok Inc.
• Collaborators: CMG Pharmaceutical Co. Ltd
• Investigators: Principal Investigator: Dong-Wan Kim, MD, PhD, Seoul National University Hospital; Principal Investigator: Tak Yun, MD, PhD, National Cancer Center; Principal Investigator: Sang-Joon Shin, MD, PhD, Severance Hospital; Principal Investigator: Yong-Wha Moon, MD, PhD, CHA Bundang Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 9, 2019
• Primary Completion (ACTUAL): January 22, 2021
• Study Completion (ACTUAL): January 29, 2021

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (ACTUAL): July 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: tropomyosin receptor kinase; Solid organ malignancies
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NOV160101-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No