A study to assess the Safety, Tolerability, Pharmacokinetics and Anti tumor Efficacy of DZD9008 in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR or HER2 mutation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dizal Pharmaceutical Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Mar 2022 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dizal (Jiangsu) Pharmaceutical Co., Ltd, China

External identifiers

EU CT number

2024-512127-36-00

EudraCT number

2019-003126-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

Part A of the study (Phase I):
. To investigate the safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC with EGFR or HER2 mutations
. To establish Maximum Tolerated Dose (MTD) (if possible) and Recommended Phase 2 Dose (PR2D) of DZD9008 when given orally in patients with advanced NSCLC with EGFR or HER2 mutations

Part B of the study (Phase II):
. To evaluate anti-tumor activity of DZD9008 in advanced NSCLC patients with EGFR Exon20ins at defined dose(s) by assessment of Objective Response Rate (ORR)

Secondary objectives 1

1. Part A of the study (Phase I): . To characterize the pharmacokinetics (PK) of DZD9008 following a single oral dosing and at steady state after multiple oral dosing in the fasted state, and renal excretion of DZD9008 . To evaluate the effect of food on the exposure of DZD9008 at the defined doses . To assess preliminary anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator . To retrospectively assess anti-tumor activity of DZD9008 in patients with EGFR Exon20ins according to RECIST 1.1 by Independent Review Committee (IRC) Part B of the study (Phase II): . To assess anti-tumor efficacy of DZD9008 using additional endpoints . To determine the safety and tolerability of DZD9008 . To characterize the PK of DZD9008

Conditions and MedDRA coding

Non-Small Cell Lung Cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

IPD plan description

not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1.Patients must be able to understand the nature of the trial and provide a signed and dated, written informed consent form prior to any study specific procedures, sampling and analyses
2. 2.Aged at least 18 years old
3. 3.Histological or cytological confirmed locally advanced or metastatic NSCLC.
4. 4.Patients must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 at ICF signature with no deterioration over the previous 2 weeks
5. 5.Predicted life expectancy ≥ 12 weeks
6. 6.Patient must have measurable disease according to RECIST 1.1:
7. 7.Patients with brain metastasis (BM) can only be enrolled under the condition that BM is previously treated and stable, neurologically asymptomatic and not require corticosteroid treatment.
8. 8.Adequate organ system functions
9. Part A of the study (Phase I) Dose escalation Patients must have documented histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations, and have relapsed from, been refractory to or are intolerant to prior standard therapy without preferred alternative therapy. Dose expansion Dose expansion cohort 1 and cohort 2: NSCLC patients with EGFR Exon20ins or HER2 Exon20ins, who have relapsed from, been refractory to or are intolerant to at least one line of prior systemic therapy Dose expansion cohort 3 and cohort 4: NSCLC patients with EGFR Exon20ins, who have relapsed from, been refractory to or are intolerant to at least one line of prior systemic therapy Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins, who have not received prior systemic therapy (treatment naïve) Dose expansion cohort 6: NSCLC patients with EGFR Exon20ins, who have recevied at least one line of prior systemic therapy, and must have relapsed from, been refractory to or intolerant to Amivantamab treatment
10. Part B of the study (Phase II): Patients must have histologically or cytologically confirmed locally advanced or metastatic NSCLC with documented EGFR Exon20ins mutation in tumor tissue from a local CLIAcertified laboratory (or equivalent) or Sponsor designated central laboratory prior to the study entry. Patients should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease .

Exclusion criteria 11

1. 1.Treatment with any of the followings: •For expansion cohorts of Part A and Part B extension cohorts: Patients who have received prior Poziotinib, TAK-788, or any other EGFR/HER2 exon20ins small molecule inhibitors treatment should be excluded. Other EGFR TKIs, such as gefitinib, erlotinib, osimertinib, afatinib, dacomitinb are allowed unless the patient had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI. •Treatment with EGFR or HER2 antibodies or other antibodies within 4 weeks before the first administration of DZD9008. •Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before the first administration of DZD9008. •Major surgery (excluding placement of vascular access) within 4 weeks before the first administration of DZD9008. •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 of DZD9008. •Patients currently receiving (or unable to stop using) medications known to be potent inhibitors or inducers of CYP3A within 1 week or 2 weeks, respectively, before the first administration of DZD9008. •Prior treatment with any onco-immunotherapy (e.g. immune checkpoint inhibitors PD-1, PD-L1, CTLA-4) within 4 weeks before the first administration of DZD9008.
2. 2. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting DZD9008 with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy.
3. 3.Spinal cord compression or leptomeningeal metastasis.
4. 4.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).
5. 5.Any of the following cardiac criteria • Mean resting corrected QT interval (QTc) > 470 msec (if in France and Canada: >470 msec for women or > 450 msec for men) obtained from 3 electrocardiograms (ECGs) at screening. •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. •Any factors that increase the risk of QTc 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. •Prior history of atrial fibrillation within 6 months of first administration of DZD9008, except prior drug treatment related and recovered.
6. 6.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.
7. 7.Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of DZD9008.
8. 8.History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with a similar chemical structure or class to DZD9008.
9. 9.Women who are pregnant or breast feeding
10. 10.Involvement in the planning and conduct of the study. Y
11. 11. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. In Part A, the primary endpoints for determining the MTD and RP2D are the incidence of dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs) and abnormal laboratory test results. The RP2D definition will be based on integrated analysis of PK, tolerability or anti-tumor efficacy data. In Part B, the primary endpoints for determining anti-tumor efficacy is ORR according to RECIST 1.1 by Independent Review Committee (IRC).

Secondary endpoints 2

1. Part A of the study (Phase I): •PK assessment includes concentrations of DZD9008 in plasma and/or urine of individual patient (secondary) •Preliminary assessment of anti-tumor efficacy includes the objective response rate (ORR), which includes the number of CR and PR based on RECIST v1.1, disease control rate (DCR), and duration of response (DoR) (secondary) •The effect of food on PK of DZD9008 (secondary) •To retrospectively assess anti-tumor activity of DZD9008 in patients with EGFR Exon20ins
2. Part B of the study (Phase II): •Safety and tolerability, including adverse events (AEs), serious adverseevents (SAEs) and abnormal laboratory test results (secondary) •PK assessment includes concentrations of DZD9008 in plasma of individual patient (secondary) •Additional anti-tumor efficacy endpoints include BOR, DOR, PFS and overall survival (OS) (secondary).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dizal Pharmaceutical Co. Ltd.

Sponsor organisation

Dizal Pharmaceutical Co. Ltd.

Address

No 199 Liangjing Road, Zhangjiang Hi Tech Park Pudong Zhangjiang Hi Tech Park Pudong

City

Shanghai

Postcode

201203

Country

China

Scientific contact point

Organisation

Dizal Pharmaceutical Co. Ltd.

Contact name

Yun He

Public contact point

Organisation

Dizal Pharmaceutical Co. Ltd.

Contact name

Yun He

Third parties 7

Locations

3 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications