Osimertinib Plus Dalpiciclib in Patients With EGFR-mutant, CDK4/6 Pathway Aberrant, Advanced Non-small Cell Lung Cancer Following Acquired Resistance to Third-generation EGFR TKI: a Phase II Trial

NCT06363734 | Recruiting Phase 2

• 1 other identifier: DAL20240409
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, single-arm, phase II trial. It is aimed to evaluate the efficacy and safety of the combination of osimertinib and dalpiciclib in patients with EGFR-mutant, CDK4/6 pathway aberrant, advanced NSCLC following acquired resistance to third-generation EGFR TKI.

Conditions

Non-small Cell Lung Cancer; EGFR Activating Mutation; Cell Cycle Deregulation; EGFR-TKI Resistant Mutation

Keywords

NSCLC; EGFR activating mutations; Third-generation EGFR-TKI; Cell cycle signaling pathway aberrations; CDK4/6 inhibitors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  12 months

Secondary Outcomes (3)

• disease control rate (DCR)

  12 months

• Duration of Response (DoR)

  12 months

• Progression Free Survival (PFS)

  12 months

Study Arms (1)

osimertinib in combination with dalpiciclib

EXPERIMENTAL

Drug: Osimertinib plus Dalpiciclib

Interventions

Osimertinib plus Dalpiciclib DRUG

osimertinib 80mg daily plus dalpiciclib 125mg daily for 21 days followed by 7 days off in each 28-day treatment cycle

osimertinib in combination with dalpiciclib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status 0 to 2 with a minimum life expectancy of 12 weeks
• Advanced non-small cell lung cancer with EGFR-sensitive mutation
• Confirmed medical history of acquired resistance to third-generation EGFR TKI
• Concurrent CDK4/6 pathway gene dysfunctional aberrations
• Evaluable or measurable disease as defined by RECIST, Version 1.1
• At least one prior line of systemic chemotherapy
• Adequate organ function

You may not qualify if:

• Prior treatment with any CDK4/6 inhibitor
• Active uncontrolled/unstable CNS metastases, carcinomatous meningitis, or leptomeningeal disease
• Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior platinum therapy related neuropathy.
• active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhoea Grade ≥2, malabsorption syndrome or previous significant bowel resection).
• Unstable angina pectoris, Congestive heart failure, Acute myocardial infarction, Stroke or transient ischemic attack or other uncontrolled cardiovascular disease currently or within the last 6 months, Mean resting correct QT interval (QTcF) \>470 msec for women and \>450 msec for men at Screening, obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value.
• Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
• Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days
• Evidence of severe or uncontrolled systemic diseases, including renal transplant, active bleeding diatheses or uncontrolled hypertension
• Active hepatitis B or C or known serious active infection e.g. tuberculosis or human immunodeficiency virus. Viral testing is not required for assessment of eligibility for the study.
• Known serious active infection including, but not limited to, tuberculosis, or human immunodeficiency virus (positive human immunodeficiency virus 1/2 antibodies).
• Presence of other active cancers, or history of treatment for invasive cancer, within the last 5 years.
• Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks prior to start of study treatment.
• Past medical history of interstitial lung disease(ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement, with or without normal LFTs,
• Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days prior to the first dose of study treatment with the exception of monotherapy osimertinib which may continue uninterrupted during screening.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Department of Thoracic Medical Oncology, Tianjin Medical University Cancer Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; dalpiciclib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: April 12, 2024
• Study Start: April 9, 2024
• Primary Completion: December 15, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 16, 2024

Record last verified: 2024-04

Locations

CN (1)