A Phase I/II, Open-Label, Multicenter 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. This study includes dose escalation (Part A)
and dose expansion (Part B).
1. Aged at least 18 years old (≥ 20 if in Japan), 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
stable, neurologically asymptomatic and does not require corticosteroid treatment.
7. Adequate organ system function.
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 dacomitinb, are allowed.
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 screening.
3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a
previous treatment regimen or clinical study within 14 days before screening.
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
5. Receiving (or unable to stop using) medications or herbal supplements known to be
potent inhibitors or inducers of CYP3A within 2-3 weeks before screening.
6. Grapefruit, grapefruit juice, and orange marmalade (made with Seville oranges) within
1 week before screening.
7. 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
8. Spinal cord compression or leptomeningeal metastasis.
9. 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 and human immunodeficiency virus (HIV).
10. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTcF) >
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 QTcF 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
11. 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
12. 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
13. History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with
a similar chemical structure or class to DZD9008
14. Women who are pregnant or breast feeding
15. Involvement in the planning and conduct of the study.
16. 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