Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)

Phase 2Active Not RecruitingNCT03974022

Dizal Pharmaceuticals315 enrolled

Overview

This study will treat patients with advanced NSCLC with EGFR or HER2 mutation who have progressed following prior therapy. This is the first time this drug is tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and preliminarily assess its anti-cancer activity as monotherapy.

A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of Sunvozertinib in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR or HER2 mutation. This study includes dose escalation, dose expansion, food effect (Part A) and dose extension (Part B).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

315

Conditions

Non-Small Cell Lung Cancer

Interventions

SunvozertinibDRUG

Daily dose of Sunvozertinib

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Aged at least 18 years old, be able to provide a signed and dated, written informed consent. 2. With documented histological or cytological confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations. 3. (ECOG) performance status 0-1. 4. Predicted life expectancy ≥ 12 weeks 5. Patient must have measurable disease according to RECIST 1.1. 6. Patients with brain metastasis (BM) can be enrolled under the condition that BM is previously treated and stable, neurologically asymptomatic and does not require corticosteroid treatment. 7. Adequate organ system function. 8. Part A Dose expansion: Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins, who have not received prior systemic therapy (treatment naïve). Part B Dose extension: 9. Patients must have histologically or cytologically confirmed locally advanced or metastatic NSCLC with documented EGFR Exon20ins mutation in tumor tissue from a local CLIA-certified laboratory (or equivalent) or Sponsor designated central laboratory prior to the study entry. 10. Patients should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease. Exclusion Criteria: 1. For part B: Patients who have received prior treatment with Poziotinib or TAK788 or other EGFR/HER2 exon20 insertion inhibitors should be excluded. Prior treatment with currently approved EGFR TKIs for sensitizing or T790M resistance mutations, such as gefitinib, erlotinib, osimertinib, afatinib and dacomitinib, are allowed unless the patient had an objective response and subsequent progression assessed by the investigator. 2. Treatment with EGFR or HER2 antibodies, major surgery (excluding placement of vascular access), or onco-immunotherapy (e.g. immune checkpoint inhibitors PD-1, PD-L1, CTLA-4) within 4 weeks before the first administration of Sunvozertinib. 3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before the first administration. 4. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose or with a wide field of radiation which must be completed within 4 weeks before the first administration. 5. Receiving (or unable to stop using) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A within 1-2 weeks before the first administration. 6. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting Sunvozertinib with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy. 7. Spinal cord compression or leptomeningeal metastasis. 8. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C, human immunodeficiency virus (HIV) and COVID-19 (per local practice). 9. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs); (2) Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block, and second-degree heart block, PR interval \> 250 msec. (3) Any factors that increase the risk of QTF prolongation, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval; (4) Prior history of atrial fibrillation within 6 months of first administration of Sunvozertinib, except prior drug treatment related and recovered. 10. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. 11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Sunvozertinib. 12. History of hypersensitivity to active or inactive excipients of Sunvozertinib or drugs with a similar chemical structure or class to Sunvozertinib. 13. Women who are pregnant or breast feeding. 14. Involvement in the planning and conduct of the study. 15. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Locations (124)

Outcomes

Primary Outcomes

Part A Dose Escalation: Dose Limiting Toxicities (DLTs).

To evaluate the safety and tolerability and defined the maximum tolerated dose (MTD) of sunvozertinib. DLT was evaluated in the DLT observation frame.

Time frame: The DLT observation period is defined as the 28 days after the first multiple dose (up to 36 days from baseline).

Part B: Objective Response Rate (ORR) According to RECIST 1.1 by an Independent Review Committee (IRC).

To evaluate anti-tumor activity of Sunvozertinib in advanced NSCLC patients with EGFR Exon20 insertion at defined dose(s) by assessment of Objective Response Rate (ORR).

Time frame: through the study completion, an average of around 1 year for part B

Secondary Outcomes

Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1

To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.

Time frame: Through the study completion, an average of around 1 year for part B

Part B: DoR, PFS According to RECIST 1.1 Using Assessments Performed by an IRC; DoR, PFS Using Investigators Assessments According to RECIST 1.1

To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.

Time frame: Through the study completion, an average of around 1 year for part B

Part B: AEs/SAEs

To determine the safety and tolerability of Sunvozertinib: Number of Participants With AEs, Number of Participants With SAEs. Using investigator reported AEs according to CTCAE and SAE criteria.

Time frame: Through the study completion, an average of around 1 year for part B

Part A: Confirmed ORR and DCR by Investigator.

Data from ClinicalTrials.gov

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University of California, San Diego (UCSD) - Moores Cancer Center

La Jolla, California, United States

University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center

Orange, California, United States

Innovative Clinical Research Institute, LLC

Whittier, California, United States

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Michigan Center of Medical Research

Farmington Hills, Michigan, United States

Northwell Health - Centers for Advanced Medicine

New Hyde Park, New York, United States

Laura and Isaac Perlmutter Cancer Center

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

...and 114 more locations

To assess preliminary anti-tumor activity of sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. Confirmed ORR was defined as the percentage of patients achieving a CR (Complete Response) or PR (Partial Response) and was confirmed by subsequent tumor assessment at least 4 weeks within the study period. Confirmed DCR was defined as the proportion of patients with a best overall response of CR, PR, or SD. Patients who achieved a CR or PR must be confirmed by a subsequent tumor assessment at least 4 weeks within the study period. Patients who achieved a best overall response of SD must be confirmed by subsequent tumor assessment at least 35 days within the study period.

Time frame: The study duration was from the initiation of sunvozertinib treatment until the study completion. The median study duration was 10 months, and the maximal study duration was 51.4 months for part A.

Part A: DoR and PFS by Investigator.

To assess preliminary anti-tumor activity of sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. DoR was presented for patients with confirmed objective response (CR or PR). DoR was the time from date of first documentation of CR or PR, which was subsequently confirmed, to date of first documentation of objective progression or death. Patients who had no documentation of objective progression or death was censored. PFS was the time from first dose date of sunvozertinib to date of first documentation of progression or death due to any cause, whichever occurred first. Patient who had no PFS event was censored.

Time frame: The maximum median of DoR was 19.3 months, and the maximum median of PFS was 12.5 months for part A.

Part A: Confirmed ORR and DCR by Independent Review Committee (IRC).

To retrospectively assess anti-tumor activity of sunvozertinib in treatment-naive NSCLC patients with EGFR Exon20ins according to RECIST 1.1 by IRC. Confirmed ORR was defined as the percentage of patients achieving a CR or PR and was confirmed by subsequent tumor assessment at least 4 weeks within the study period. Confirmed DCR was defined as the proportion of patients with a best overall response of CR, PR, or SD. Patients who achieved a CR or PR must be confirmed by subsequent tumor assessment at least 4 weeks within the study period. Patients who achieved a best overall response of SD must be confirmed by subsequent tumor assessment at least 35 days within the study period.

Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008

Maximum observed plasma concentration (ng/mL), obtained directly from the observed concentration versus time data. Calculated for the single dose.

Time frame: Cycle 0 Day 1: 0 (predose) up to 168 hours (for Part A escalation); Cycle 1 Day 1: 0 (predose) up to 24 hours (for Part A expansion)

Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008

Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule.

Time frame: Cycle 0 Day 1: 0 (predose) up to 168 hours (for Part A escalation); Cycle 1 Day 1: 0 (predose) up to 24 hours (for Part A expansion)

Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008

Maximum observed plasma concentration(ng/mL), at steady state, obtained directly from the observed concentration versus time data. Calculated for the multiple dose.

Time frame: Cycle 2 Day 1: 0 (predose) up to 24 hours (for Part A Dose expansion and expansion)

Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008

Area under the plasma concentration-time curve in the dose interval at steady state, calculated by the linear up/log down rule.

Time frame: Cycle 2 Day 1: 0 (predose) up to 24 hours (for Part A Dose escalation and expansion)

Part A Food Effect: Maximum Plasma Concentration (Cmax) of DZD9008

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose, in the fasted or fed state.

Time frame: Day 1 and Day 9: 0 (predose) up to 168 hours.

Part A Food Effect: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008

Area under the plasma concentration-time-curve from time zero the last quantifiable time point, calculated by the linear up/log down rule, in the fasted or fed state.

Time frame: Day 1 and Day 9: 0 (predose) up to 168 hours.

Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose.

Time frame: Cycle 1 Day 1: 0 (predose) up to 24 hours

Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753.

Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule.

Time frame: Cycle 1 Day 1: 0 (predose) up to 24 hours

Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the multiple dose.

Time frame: Cycle 2 Day 1: 0 (predose) up to 24 hours

Part B: AUCss, at Steady State of DZD9008 and DZ0753.

Area under the plasma concentration-time curve from time zero in the dose interval at steady state, calculated by the linear up/log down rule.

Time frame: Cycle 2 Day 1: 0 (predose) up to 24 hours