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Clinical Trial 20409

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03974022

Phase: Phase I/II
Principal Investigator: Pellini, Bruna

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Overview

Study Title

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

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.

Objective

Part A (dose escalation) Primary Objectives: 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 Secondary Objectives: To characterize the pharmacokinetics (PK) of DZD9008 following a single oral dosing and at steady state after multiple oral dosing, and renal excretion of DZD9008 To evaluate the effect of food on the exposure of DZD9008 following single oral dosing at defined dose level To assess preliminary anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Exploratory Objectives: To collect and store diagnostic tumor samples (archived) or any fresh tumor biopsies (if archived tumor sample is not available) to confirm EGFR and HER2 mutations by central lab retrospectively, support the development of diagnostic test for pre-market approval by regulatory authorities and potential future exploratory research into factors that may influence development of DZD9008 in NSCLC and/or tumor response to DZD9008 To investigate the presence, and/or identity of the drug metabolites of DZD9008 in plasma and urine samples, if appropriate, characterize their PK To collect and store blood-based samples for future exploratory research on genes/genetic aberrations that may influence response to DZD9008 treatment and/or susceptibility to DZD9008 Part B Primary Objective: To evaluate anti-tumor activity of DZD9008 in advanced NSCLC patients with EGFR Exon20ins, HER2 Exon20ins or EGFR uncommon mutation at defined dose(s) Secondary Objectives: To determine the safety and tolerability of DZD9008 To characterize the PK of DZD9008 at steady state To assess anti-tumor efficacy of DZD9008 using additional endpoints Exploratory Objectives: To collect and store diagnostic tumor samples (archived) or any fresh tumor biopsies (if archived tumor sample is not available) to confirm EGFR and HER2 mutations by central lab retrospectively, support the development of diagnostic test for pre-market approval by regulatory authorities and potential future exploratory research into factors that may influence development of DZD9008 in NSCLC and/or tumor response to DZD9008 To collect and store blood-based samples for future exploratory research on genes/genetic aberrations that may influence response to DZD9008 treatment and/or susceptibility to DZD9008 To investigate the effect of DZD9008 on proof-of-mechanism (PoM) biomarkers in tumor biopsy (e.g. EGFR phosphorylation (pEGFR))

Treatments

Therapies

Therapy (NOS)

Medications

DZD9008 ()

Inclusion Criteria

Inclusion Criteria:

  • Aged at least 18 years old, be able to provide a signed and dated, written informed consent.
  • Documented histological or cytological confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations.
  • (ECOG) performance status 0-1.
  • Predicted life expectancy ≥ 12 weeks
  • Patient must have measurable disease according to RECIST 1.1.
  • Patients with brain metastasis (BM) can be enrolled under the condition that BM is stable, neurologically asymptomatic and does not require corticosteroid treatment.
  • Adequate organ system function.
  • Other criteria may apply

  • Exclusion Criteria

    Exclusion Criteria:

  • 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.
  • 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.
  • Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before screening.
  • 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 screening.
  • 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.
  • Grapefruit, grapefruit juice, and orange marmalade (made with Seville oranges) within 1 week before screening.
  • 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.
  • Spinal cord compression or leptomeningeal metastasis.
  • 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).
  • 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
  • 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
  • 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
  • History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with a similar chemical structure or class to DZD9008
  • Women who are pregnant or breast feeding
  • Involvement in the planning and conduct of the study.
  • 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.
  • Other criteria may apply

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