Assessing the Effect of DZD9008 on the Pharmacokinetics of the Cocktail Probes Representative for CYP3A4, P-gp, BCRP and OATP1B1 in Patients with EGFR or HER2 Mutant Advanced Non-small Cell Lung Cancer (WU-KONG19)

NCT05926180 | Completed Phase 1 FDA Drug

• 1 other identifier: DZ2021E0009
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study will treat patients with advanced NSCLC who have progressed following prior therapy in order to assess the effect of DZD9008 on exposure of midazolam, digoxin and rosuvastatin, through multiple PK parameters, when administrated as a single dose alone and in combination with DZD9008. Also, it will assess the safety and tolerability of DZD9008 in the presence and absence of co-administration of cocktail probes.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008

  Days 1-35

• AUC0-t of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008

  Days 1-35

• Ratio of AUC of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008

  Days 1-35

• Ratio of Cmax of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008

  Days 1-35

• AUC0-inf of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008, if applicable

  Days 1-35

Study Arms (1)

DZD9008 + Probe Drugs

EXPERIMENTAL

Single dose of 2 mg midazolam (oral solution), 0.25 mg digoxin (tablet) and 10mg rosuvastatin (tablet) and in combination with 300 mg DZD9008 (tablet)

Drug: DZD9008 and Probe drugs (midazolam, digoxin, rosuvastatin)

Interventions

DZD9008 and Probe drugs (midazolam, digoxin, rosuvastatin) DRUG

Patients will receive single oral doses of probe drugs alone and after at least 27 days of treatment with DZD9008, 300 mg, once daily, until a treatment discontinuation criterion is met. Each patient will receive a single oral dose of DZD9008 on Day 7, and DZD9008 once daily for 27 days from Day 9 to Day 35. Patients will also receive a single oral dose of 2 mg midazolam on Day 1 and Day 32, and oral dose of 10 mg rosuvastatin and 0.25 mg digoxin cocktail on Day 2, Day 7 and Day 33.

Also known as: Inapplicable

DZD9008 + Probe Drugs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged at least 18 years old, be able to provide a signed and dated, written informed consent.
• Patients must have documented histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations and have progressed from, been refractory to or are intolerant to prior standard therapy without preferred alternative therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 at ICF signature with no deterioration over the previous 2 weeks.
• Predicted life expectancy ≥ 12 weeks

You may not qualify if:

• Patients with a known hypersensitivity to DZD9008, rosuvastatin, digoxin, midazolam, or any of the excipients of the products.
• Concomitant medication or any clinical condition contraindicated for use with rosuvastatin, digoxin, midazolam.
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4, BCRP, OATP1B1 and P-gp.
• Patients who have BCRP (ABCG2) polymorphism c.421C\>A (p.Q141K, rs2231142).
• Patients with previous allogenic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
• Patients with liver metastases, spinal cord compression or leptomeningeal metastasis.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.
• Participants with active infection including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) (refer to CSP) and active infection of COVID-19.
• Inadequate bone marrow reserve or organ function.
• 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 study treatment.
• Women who are pregnant or breast feeding.
• Known history of bleeding diathesis, i.e., hemophilia, Von Willebrand disease.
• History of stroke or intracranial haemorrhage within 6 months

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (1)

Shandong Cancer Hospital (Shandong Provincial Institute of Cancer Prevention and Treatment)

Jinan, Shandong, 250117, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Midazolam; Digoxin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2023
• First Posted: July 3, 2023
• Study Start: July 31, 2023
• Primary Completion: May 16, 2024
• Study Completion: September 28, 2024
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)