Clinical trial NCT05926180: 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)
Official title: A Phase 1, Open-label, Non-Randomized Study to Assess 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Dizal Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-07-03
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Cmax of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
timeFrame: Days 1-35
measure: AUC0-t of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008
timeFrame: Days 1-35
measure: Ratio of AUC of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
timeFrame: Days 1-35
measure: Ratio of Cmax of midazolam, 1-OH midazolam, digoxin and rosuvastatin between substrate alone and with DZD9008
timeFrame: Days 1-35
measure: AUC0-inf of midazolam, 1-OH Midazolam, digoxin and rosuvastatin alone and in combination with DZD9008, if applicable
timeFrame: Days 1-35
Secondary outcomes:
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital (Shandong Provincial Institute of Cancer Prevention and Treatment)
state: Shandong
Study officials:
References: