D-0316 First Time in Patients Ascending Dose Study

A Phase I Study of D-0316 in Patients With Advanced Non Small Cell Lung Cancer With Mutation of Epidermal Growth Factor Receptor Tyrosine Kinase

This is a phase 1 open label multicentre study of D-0316 administered orally in patients with advanced NSCLC who have progressed following prior therapy with an EGFR-TKI (Epidermal Growth Factor Receptor tyrosine kinase inhibitor agent). This is the first time this drug has ever been tested in patients, and so it will help to understand safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of ascending doses of D-0316.

Study Overview

• Status: Completed
• Conditions: Advanced Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: D-0316

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130012
      • Research Site
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Research Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
• Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC).
• Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib. In addition other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
• Confirmation that the tumour harbours an EGFR T790M mutation.
• No deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
• Evaluable or measurable disease per RECIST v1.1

Exclusion Criteria:

• Treatment with an EGFR TKI (erlotinib or gefitinib) within 14 days of the first dose of study treatment.
• Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.

Other protocol defined inclusion/exclusion criteria could apply

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: Daily oral dose of D-0316	Drug: D-0316; If initial dosing of D-0316 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose or maximum feasible dose is defined

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs)	Incidence of DLTs	Day 1 - Day 28
Adverse events	Incidence of AEs	Day 1 - Day 28
Laboratory results	Incidence of laboratory abnormalities	Day 1 - Day 28
Vital signs	Incidence of vital sign abnormalities	Day 1 - Day 28
Electrocardiogram	Incidence of ECG abnormalities	Day 1 - Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic: area under the plasma concentration versus time curve (AUC)	AUC: area under the plasma concentration versus time curve for D-0316	Day 1 through 6, Cycle Day 1-Day 15
Pharmacokinetic: maximum plasma drug concentration (Cmax)	Cmax: maximum plasma drug concentration of D-0316	Day 1 through 6, Cycle Day 1-Day 15
Pharmacokinetic: Time to reach the Cmax (Tmax)	tmax: Time to reach the Cmax of D-0316	Day 1 through 6, Cycle Day 1-Day 15
Pharmacokinetic: Apparent terminal half-life (t1/2)	t1/2: apparent terminal half-life of D-0316	Day 1 through 6, Cycle Day 1-Day 15
Antitumor activity	Antitumor activity by evaluation of tumor response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Collaborators and Investigators

• Sponsor: InventisBio Co., Ltd

Publications and helpful links

General Publications

• Jian H, Wang K, Cheng Y, Ding L, Wang Y, Shi Z, Zhang L, Wang Y, Lu S. Phase I Trial of a Third Generation EGFR Mutant-Selective Inhibitor (D-0316) in Patients with Advanced Non-Small Cell Lung Cancer. Oncologist. 2022 Mar 11;27(3):163-e213. doi: 10.1093/oncolo/oyab007.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2018
• Primary Completion (Actual): August 28, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 28, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: XY-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