Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, EGFR, HER2, mutation
Brief summary
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.
Detailed description
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).
Interventions
DRUGSunvozertinib
Daily dose of Sunvozertinib
Sponsors
Dizal Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A Dose Escalation: Dose Limiting Toxicities (DLTs). | The DLT observation period is defined as the 28 days after the first multiple dose (up to 36 days from baseline). | To evaluate the safety and tolerability and defined the maximum tolerated dose (MTD) of sunvozertinib. DLT was evaluated in the DLT observation frame. |
| Part B: Objective Response Rate (ORR) According to RECIST 1.1 by an Independent Review Committee (IRC). | through the study completion, an average of around 1 year for part B | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1 | Through the study completion, an average of around 1 year for part B | To assess anti-tumor efficacy of Sunvozertinib using additional endpoints. |
| 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 | Through the study completion, an average of around 1 year for part B | To assess anti-tumor efficacy of Sunvozertinib using additional endpoints. |
| Part B: AEs/SAEs | Through the study completion, an average of around 1 year for part B | 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. |
| Part A: Confirmed ORR and DCR by Investigator. | 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. | 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. |
| Part A: DoR and PFS by Investigator. | The maximum median of DoR was 19.3 months, and the maximum median of PFS was 12.5 months for part A. | 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. |
| Part A: Confirmed ORR and DCR by Independent Review Committee (IRC). | 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. | 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 | 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) | Maximum observed plasma concentration (ng/mL), obtained directly from the observed concentration versus time data. Calculated for the single dose. |
| Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 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) | Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule. |
| Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | Cycle 2 Day 1: 0 (predose) up to 24 hours (for Part A Dose expansion and expansion) | Maximum observed plasma concentration(ng/mL), at steady state, obtained directly from the observed concentration versus time data. Calculated for the multiple dose. |
| Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | Cycle 2 Day 1: 0 (predose) up to 24 hours (for Part A Dose escalation and expansion) | Area under the plasma concentration-time curve in the dose interval at steady state, calculated by the linear up/log down rule. |
| Part A Food Effect: Maximum Plasma Concentration (Cmax) of DZD9008 | Day 1 and Day 9: 0 (predose) up to 168 hours. | Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose, in the fasted or fed state. |
| Part A Food Effect: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | Day 1 and Day 9: 0 (predose) up to 168 hours. | 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. |
| Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753 | Cycle 1 Day 1: 0 (predose) up to 24 hours | Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose. |
| Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753. | Cycle 1 Day 1: 0 (predose) up to 24 hours | Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule. |
| Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753 | Cycle 2 Day 1: 0 (predose) up to 24 hours | Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the multiple dose. |
| Part B: AUCss, at Steady State of DZD9008 and DZ0753. | Cycle 2 Day 1: 0 (predose) up to 24 hours | 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. |
Countries
Argentina, Australia, Canada, Chile, China, France, Italy, Japan, Malaysia, South Korea, Spain, Taiwan, United States
Contacts
PRINCIPAL_INVESTIGATORPasi Antero Jänne, M.D & Ph. D
Dana-Farber Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg Patients with EGFR or HER2 mutations, previously treated with at least one line of systemic therapy.
Patients received a single dose of 50 mg sunvozertinib, followed by a 7-day washout period. Then, they received 50 mg sunvozertinib once daily continuously. | 3 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg Patients with EGFR or HER2 mutations, previously treated with at least one line of systemic therapy.
Patients received a single dose of 100 mg sunvozertinib, followed by a 7-day washout period. Then, they received 100 mg sunvozertinib once daily continuously. | 6 |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg Patients with EGFR or HER2 mutations, previously treated with at least one line of systemic therapy.
Patients received a single dose of 200 mg sunvozertinib, followed by a 7-day washout period. Then, they received 200 mg sunvozertinib once daily continuously. | 3 |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg Patients with EGFR or HER2 mutations, previously treated with at least one line of systemic therapy.
Patients received a single dose of 300 mg sunvozertinib, followed by a 7-day washout period. Then, they received 300 mg sunvozertinib once daily continuously. | 7 |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg Patients with EGFR or HER2 mutations, previously treated with at least one line of systemic therapy.
Patients received a single dose of 400 mg sunvozertinib, followed by a 7-day washout period. Then, they received 400 mg sunvozertinib once daily continuously. | 6 |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State Patients with EGFR or HER2 exon20ins, previously treated with at least one line of systemic therapy.
Patients received sunvozertinib 200 mg once daily dosing in the fasted state continuously. | 10 |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State Patients with EGFR or HER2 exon20ins, previously treated with at least one line of systemic therapy.
Patients received sunvozertinib 300 mg once daily dosing in the fasted state continuously. | 14 |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal Patients with EGFR exon20ins, previously treated with at least one line of systemic therapy.
Patients received sunvozertinib 200 mg once daily dosing with a low-fat meal continuously. | 14 |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal Patients with EGFR exon20ins, previously treated with at least one line of systemic therapy.
Patients received sunvozertinib 300 mg once daily dosing with a low-fat meal continuously. | 7 |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal Patients with EGFR exon20ins, treatment naïve. Patients received sunvozertinib 300 mg once daily dosing with a low-fat meal continuously. | 31 |
| Part A Dose Expansion Cohort 6: Previously Treated With Amivantamab; Sunvozertinib 300 mg Patients with EGFR exon20ins, were refractory to, relapsed from, or intolerant to previous amivantamab treatment.
No patient was enrolled into this cohort. | 0 |
| Part A Food Effect Cohort 1: Sunvozertinib 300 mg; High-Fat Meal Condition First, Then Fasted Patients with EGFR exon20ins, previously treated with at least one line of systemic therapy.
Patients were randomized at a 1:1 ratio to receive a single dose of sunvozertinib 300 mg under the High-Fat Meal condition, followed by a 7-day washout and crossed to receive a single dose of sunvozertinib 300 mg under the Fasted condition, followed by a 7-day washout. Then patients received sunvozertinib 300 mg once daily continuously. | 5 |
| Part A Food Effect Cohort 2: Sunvozertinib 300 mg; Fasted Condition First, Then High-Fat Meal Patients with EGFR exon20ins, previously treated with at least one line of systemic therapy.
Patients were randomized at a 1:1 ratio to receive a single dose of sunvozertinib 300 mg under the Fasted condition, followed by a 7-day washout and crossed to receive a single dose of sunvozertinib 300 mg under the High-Fat Meal condition, followed by a 7-day washout. Then patients received sunvozertinib 300 mg once daily continuously. | 7 |
| Part B Dose Extension Cohort 1: EGFR exon20ins, Previously Treated; Sunvozertinib 200 mg Patients with EGFR exon20ins, previously treated with at least one line of systemic therapy.
Patients were randomized to receive sunvozertinib 200 mg once daily continuously. | 91 |
| Part B Dose Extension Cohort 2: EGFR exon20ins, Previously Treated; Sunvozertinib 300 mg Patients with EGFR exon20ins, previously treated with at least one line of systemic therapy.
Patients were randomized to receive sunvozertinib 300 mg once daily continuously. | 111 |
| Total | 315 |
Baseline characteristics
| Characteristic | Total | Part B Dose Extension Cohort 2: EGFR exon20ins, Previously Treated; Sunvozertinib 300 mg | Part B Dose Extension Cohort 1: EGFR exon20ins, Previously Treated; Sunvozertinib 200 mg | Part A Food Effect Cohort 2: Sunvozertinib 300 mg; Fasted Condition First, Then High-Fat Meal | Part A Food Effect Cohort 1: Sunvozertinib 300 mg; High-Fat Meal Condition First, Then Fasted | Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Dose Expansion Cohort 6: Previously Treated With Amivantamab; Sunvozertinib 300 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.0 years | 64 years | 62 years | 65.0 years | 44.0 years | 61 years | 64 years | 60.5 years | 62.5 years | 61 years | 63.5 years | 64.0 years | 57.0 years | 62.0 years | 48.0 years | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 204 Participants | 65 Participants | 59 Participants | 0 Participants | 1 Participants | 23 Participants | 7 Participants | 13 Participants | 9 Participants | 10 Participants | 3 Participants | 5 Participants | 2 Participants | 5 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 103 Participants | 44 Participants | 30 Participants | 6 Participants | 4 Participants | 5 Participants | 0 Participants | 1 Participants | 5 Participants | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 186 Participants | 63 Participants | 61 Participants | 6 Participants | 4 Participants | 13 Participants | 2 Participants | 9 Participants | 6 Participants | 7 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 129 Participants | 48 Participants | 30 Participants | 1 Participants | 1 Participants | 18 Participants | 5 Participants | 5 Participants | 8 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 6 | 0 / 3 | 2 / 7 | 0 / 6 | 1 / 10 | 0 / 14 | 2 / 14 | 1 / 7 | 4 / 31 | 0 / 0 | 0 / 5 | 0 / 7 | 33 / 91 | 40 / 111 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 3 / 3 | 7 / 7 | 6 / 6 | 10 / 10 | 14 / 14 | 14 / 14 | 7 / 7 | 31 / 31 | 0 / 0 | 5 / 5 | 7 / 7 | 91 / 91 | 111 / 111 |
| serious Total, serious adverse events | 0 / 3 | 1 / 6 | 1 / 3 | 4 / 7 | 2 / 6 | 4 / 10 | 5 / 14 | 9 / 14 | 2 / 7 | 14 / 31 | 0 / 0 | 0 / 5 | 1 / 7 | 37 / 91 | 41 / 111 |
Outcome results
Primary
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).
Population: Patients in part A Dose Escalation Cohorts who met either or both criteria below were included in DLT analysis:~* Patients who received the single dose and at least 80% of planned doses of DZD9008 in the first 28-day of repeated dosing and completed minimum required safety evaluations.~* Patients who had at least one DLT reported during the DLT period. 1 patient in 100 mg dose level and 1 patient in 300 mg dose level received less than 80% of planned dose were excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Dose Escalation: Dose Limiting Toxicities (DLTs). | 0 Participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A Dose Escalation: Dose Limiting Toxicities (DLTs). | 0 Participants |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A Dose Escalation: Dose Limiting Toxicities (DLTs). | 0 Participants |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A Dose Escalation: Dose Limiting Toxicities (DLTs). | 1 Participants |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A Dose Escalation: Dose Limiting Toxicities (DLTs). | 1 Participants |
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Objective Response Rate (ORR) According to RECIST 1.1 by an Independent Review Committee (IRC). | 45.9 percentage of participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Objective Response Rate (ORR) According to RECIST 1.1 by an Independent Review Committee (IRC). | 45.8 percentage of participants |
p-value: <0.0001binomial exact test against H0
p-value: <0.0001binomial exact test against H0
Secondary
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.
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.
Population: Only participants in Part A were presented here, while Part B were presented separately. According to the clinical study protocol, only participants in Part A Dose Expansion Cohort 5 (treatment-naive patients) were evaluated by IRC. Therefore, we only present the IRC results from Part A Dose Expansion Cohort 5.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A: Confirmed ORR and DCR by Independent Review Committee (IRC). | Confirmed objective response rate | 62.1 percentage of participants |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A: Confirmed ORR and DCR by Independent Review Committee (IRC). | Confirmed disease control rate | 89.7 percentage of participants |
Secondary
Part A: Confirmed ORR and DCR by Investigator.
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.
Population: Only participants in Part A were presented here, while Part B were presented separately. Participants in Part A with baseline and at least one post-treatment tumor assessment were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 0 percentage of participants |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 100.0 percentage of participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 16.7 percentage of participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 50.0 percentage of participants |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 0 percentage of participants |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 66.7 percentage of participants |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 42.9 percentage of participants |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 71.4 percentage of participants |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 60.0 percentage of participants |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 0 percentage of participants |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 50 percentage of participants |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 80 percentage of participants |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 84.6 percentage of participants |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 30.8 percentage of participants |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 21.4 percentage of participants |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 92.9 percentage of participants |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 40.0 percentage of participants |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 80.0 percentage of participants |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 55.2 percentage of participants |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 93.1 percentage of participants |
| Part A Food Effect Cohort 1: Sunvozertinib 300 mg; High-Fat Meal Condition First, Then Fasted | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 60.0 percentage of participants |
| Part A Food Effect Cohort 1: Sunvozertinib 300 mg; High-Fat Meal Condition First, Then Fasted | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 20.0 percentage of participants |
| Part A Food Effect Cohort 2: Sunvozertinib 300 mg; Fasted Condition First, Then High-Fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed disease control rate | 85.7 percentage of participants |
| Part A Food Effect Cohort 2: Sunvozertinib 300 mg; Fasted Condition First, Then High-Fat Meal | Part A: Confirmed ORR and DCR by Investigator. | Confirmed objective response rate | 14.3 percentage of participants |
Secondary
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.
Population: Only participants in Part A were presented here, while Part B were presented separately. Participants in Part A with baseline and at least one post-treatment tumor assessment were included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A: DoR and PFS by Investigator. | Median duration of response(month) | NA month |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 3.1 month |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 4.0 month |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 1.9 month |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A: DoR and PFS by Investigator. | Median duration of response(month) | NA month |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 12.5 month |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 5.5 month |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 3.3 month |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 4.6 month |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A: DoR and PFS by Investigator. | Median duration of response(month) | NA month |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A: DoR and PFS by Investigator. | Median duration of response(month) | NA month |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 4.9 month |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 5.5 month |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 4.2 month |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 6.3 month |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 4.2 month |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 4.3 month |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 4.2 month |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 9.8 month |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 10.8 month |
| Part A Food Effect Cohort 1: Sunvozertinib 300 mg; High-Fat Meal Condition First, Then Fasted | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 3.3 month |
| Part A Food Effect Cohort 1: Sunvozertinib 300 mg; High-Fat Meal Condition First, Then Fasted | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 19.3 month |
| Part A Food Effect Cohort 2: Sunvozertinib 300 mg; Fasted Condition First, Then High-Fat Meal | Part A: DoR and PFS by Investigator. | Median progression free survival(month) | 5.3 month |
| Part A Food Effect Cohort 2: Sunvozertinib 300 mg; Fasted Condition First, Then High-Fat Meal | Part A: DoR and PFS by Investigator. | Median duration of response(month) | 5.6 month |
Secondary
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)
Population: All participants who have received at least one dose of study drug with at least one measurable plasma concentration of DZD9008 post dose without any important deviations or events that would exclude the participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 1434 h*ng/mL | Geometric Coefficient of Variation 45.9 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 2693 h*ng/mL | Geometric Coefficient of Variation 115.8 |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | NA h*ng/mL | — |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 12540 h*ng/mL | Geometric Coefficient of Variation 69.7 |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 6419 h*ng/mL | Geometric Coefficient of Variation 60 |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 2300 h*ng/mL | Geometric Coefficient of Variation 46 |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 3800 h*ng/mL | Geometric Coefficient of Variation 56.9 |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 3313 h*ng/mL | Geometric Coefficient of Variation 39.3 |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 4517 h*ng/mL | Geometric Coefficient of Variation 28.2 |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | 4338 h*ng/mL | Geometric Coefficient of Variation 60.3 |
Secondary
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)
Population: All participants who have received at least one dose of study drug with at least one measurable plasma concentration of DZD9008 post dose without any important deviations or events that would exclude the participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 1506 h*ng/mL | Geometric Coefficient of Variation 13.2 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 3823 h*ng/mL | Geometric Coefficient of Variation 55.6 |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | NA h*ng/mL | — |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 10240 h*ng/mL | Geometric Coefficient of Variation 78.1 |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 12030 h*ng/mL | Geometric Coefficient of Variation 25.2 |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 5906 h*ng/mL | Geometric Coefficient of Variation 52.3 |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 11630 h*ng/mL | Geometric Coefficient of Variation 40.3 |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 9949 h*ng/mL | Geometric Coefficient of Variation 45.8 |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 14170 h*ng/mL | Geometric Coefficient of Variation 47.9 |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: AUCss, at Steady State of DZD9008 | 12030 h*ng/mL | Geometric Coefficient of Variation 40.2 |
Secondary
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)
Population: All participants who have received at least one dose of study drug with at least one measurable plasma concentration of DZD9008 post dose without any important deviations or events that would exclude the participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 82.85 ng/mL | Geometric Coefficient of Variation 17.2 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 229.4 ng/mL | Geometric Coefficient of Variation 50.6 |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | NA ng/mL | — |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 590.2 ng/mL | Geometric Coefficient of Variation 80.9 |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 677.0 ng/mL | Geometric Coefficient of Variation 21.9 |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 358.0 ng/mL | Geometric Coefficient of Variation 53.4 |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 717.5 ng/mL | Geometric Coefficient of Variation 40.9 |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 613.3 ng/mL | Geometric Coefficient of Variation 48.8 |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 819.3 ng/mL | Geometric Coefficient of Variation 57.3 |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Cmax,ss, at Steady State of DZD9008 | 716.5 ng/mL | Geometric Coefficient of Variation 41.7 |
Secondary
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)
Population: All participants who have received at least one dose of study drug with at least one measurable plasma concentration of DZD9008 post dose without any important deviations or events that would exclude the participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 38.95 ng/mL | Geometric Coefficient of Variation 37.3 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 89.19 ng/mL | Geometric Coefficient of Variation 53.5 |
| Part A Dose Escalation Cohort 3: Sunvozertinib 200 mg | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | NA ng/mL | — |
| Part A Dose Escalation Cohort 4: Sunvozertinib 300 mg | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 428.8 ng/mL | Geometric Coefficient of Variation 69.2 |
| Part A Dose Escalation Cohort 5: Sunvozertinib 400 mg | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 167.8 ng/mL | Geometric Coefficient of Variation 90.7 |
| Part A Dose Expansion Cohort 1: Sunvozertinib 200 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 176.3 ng/mL | Geometric Coefficient of Variation 50.7 |
| Part A Dose Expansion Cohort 2: Sunvozertinib 300 mg, Dosing in the Fasted State | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 286.7 ng/mL | Geometric Coefficient of Variation 62.6 |
| Part A Dose Expansion Cohort 3: Sunvozertinib 200 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 253.0 ng/mL | Geometric Coefficient of Variation 44.1 |
| Part A Dose Expansion Cohort 4: Sunvozertinib 300 mg; Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 346.5 ng/mL | Geometric Coefficient of Variation 33.5 |
| Part A Dose Expansion Cohort 5: Treatment naïve, Sunvozertinib 300 mg, Dosing With a Low-fat Meal | Part A Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of DZD9008 | 354.3 ng/mL | Geometric Coefficient of Variation 68.3 |
Secondary
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.
Population: All participants from the food effect cohort for whom a PK profile is available on at least one of the fed and fasted dosing days.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Food Effect: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | Part A Food effect: AUC0-t of DZD9008 under Fasted condition | 8266 h*ng/mL | Geometric Coefficient of Variation 65.8 |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Food Effect: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 | Part A Food effect: AUC0-t of DZD9008 under High-Fat Meal condition | 10050 h*ng/mL | Geometric Coefficient of Variation 67.5 |
Secondary
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.
Population: All participants from the food effect cohort for whom a PK profile is available on at least one of the fed and fasted dosing days.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Food Effect: Maximum Plasma Concentration (Cmax) of DZD9008 | Part A Food effect: Maximum Plasma Concentration (Cmax) of DZD9008 under Fasted condition | 307.0 ng/mL | Geometric Coefficient of Variation 59.6 |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part A Food Effect: Maximum Plasma Concentration (Cmax) of DZD9008 | Part A Food effect: Maximum Plasma Concentration (Cmax) of DZD9008 under High-Fat Meal condition | 331.6 ng/mL | Geometric Coefficient of Variation 48.8 |
Secondary
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
Population: all patients had at least one dose of DZD9008
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: AEs/SAEs | Any TEAE | 91 participants |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: AEs/SAEs | Any treatment- emergent SAE | 37 participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: AEs/SAEs | Any TEAE | 111 participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: AEs/SAEs | Any treatment- emergent SAE | 41 participants |
Secondary
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
Population: All dosed participants who have at least one measurable plasma concentration of DZD9008 post dose with no protocol deviations or adverse event thought to impact the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753. | Part B: AUC0-t of DZD9008 | 2423 h*ng/mL | Geometric Coefficient of Variation 71.9 |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753. | Part B: AUC0-t of DZ0753 | 200.4 h*ng/mL | Geometric Coefficient of Variation 125.2 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753. | Part B: AUC0-t of DZD9008 | 4397 h*ng/mL | Geometric Coefficient of Variation 55.7 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of DZD9008 and DZ0753. | Part B: AUC0-t of DZ0753 | 448.5 h*ng/mL | Geometric Coefficient of Variation 69.9 |
Secondary
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
Population: All dosed participants who have at least one measurable plasma concentration of DZD9008 post dose with no protocol deviations or adverse event thought to impact the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: AUCss, at Steady State of DZD9008 and DZ0753. | Part B: AUCss, at Steady State of DZD9008 | 6286 h*ng/mL | Geometric Coefficient of Variation 56.1 |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: AUCss, at Steady State of DZD9008 and DZ0753. | Part B: AUCss, at Steady State of DZ0753 | 728.9 h*ng/mL | Geometric Coefficient of Variation 112.2 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: AUCss, at Steady State of DZD9008 and DZ0753. | Part B: AUCss, at Steady State of DZD9008 | 10230 h*ng/mL | Geometric Coefficient of Variation 47.5 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: AUCss, at Steady State of DZD9008 and DZ0753. | Part B: AUCss, at Steady State of DZ0753 | 1722 h*ng/mL | Geometric Coefficient of Variation 84.9 |
Secondary
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
Population: All dosed participants who have at least one measurable plasma concentration of DZD9008 post dose with no protocol deviations or adverse event thought to impact the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax,ss) of DZD9008 | 342.8 ng/mL | Geometric Coefficient of Variation 57.4 |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax,ss) of DZ0753 | 42.58 ng/mL | Geometric Coefficient of Variation 108 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax,ss) of DZD9008 | 642.3 ng/mL | Geometric Coefficient of Variation 48.1 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Cmax,ss, at Steady State of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax,ss) of DZ0753 | 112.4 ng/mL | Geometric Coefficient of Variation 83.7 |
Secondary
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1 | confirmed DCR by IRC | 89.4 percentage of participants |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1 | confirmed DCR by investigator | 88.2 percentage of participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1 | confirmed DCR by IRC | 88.8 percentage of participants |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: DCR According to RECIST 1.1 Using Assessments Performed by an IRC; DCR Using Investigators Assessments According to RECIST 1.1 | confirmed DCR by investigator | 88.8 percentage of participants |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | 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 | Median duration of response (IRC) | NA months |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | 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 | Median duration of response (investigator) | 8.3 months |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | 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 | Median progression free survival (IRC) | 8.4 months |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | 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 | Median progression free survival (investigator) | 8.3 months |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | 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 | Median progression free survival (investigator) | 6.8 months |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | 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 | Median duration of response (IRC) | NA months |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | 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 | Median progression free survival (IRC) | 6.9 months |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | 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 | Median duration of response (investigator) | 8.8 months |
Secondary
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
Population: All dosed participants who have at least one measurable plasma concentration of DZD9008 post dose with no protocol deviations or adverse event thought to impact the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax) of DZD9008 | 173.4 ng/mL | Geometric Coefficient of Variation 80.4 |
| Part A Dose Escalation Cohort 1: Sunvozertinib 50 mg | Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax) of DZ0753 | 18.90 ng/mL | Geometric Coefficient of Variation 113.4 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax) of DZD9008 | 325.8 ng/mL | Geometric Coefficient of Variation 73.7 |
| Part A Dose Escalation Cohort 2: Sunvozertinib 100 mg | Part B: Maximum Plasma Concentration (Cmax) of DZD9008 and DZ0753 | Part B: Maximum Plasma Concentration (Cmax) of DZ0753 | 40.40 ng/mL | Geometric Coefficient of Variation 78.2 |