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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; EGFR Activating Mutation; EGFR-TKI Resistant Mutation; Cell Cycle Deregulation
• Intervention / Treatment: Drug: Osimertinib plus Dalpiciclib

Detailed Description

After signing informed consents and completing the screening phase, eligible subjects who meet the enrolment criteria receive the treatment with once-daily osimertinib 80 mg plus dalpiciclib 125 mg daily for 21 consecutive days followed by 7 days off in each 28-day cycle until objective disease progression, intolerable toxicity, or other events that subjects need to be withdrawn from the study.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Department of Thoracic Medical Oncology, Tianjin Medical University Cancer Hospital
      • Principal Investigator: Peng Chen, M.D.
      • Contact: Peng Chen, M.D.; Phone Number: 3201 +86-22-23340123; Email: chenpeng@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers or inhibitors of CYP3A4 within 3 weeks of the first dose of study treatment
• Participation in another clinical study with a cytotoxic, investigational product (IP), or other anticancer drug for the treatment of advanced NSCLC if received IP from that study within 14 days of the first dose of study treatment.
• Known hypersensitivity to the active or inactive excipients of osimertinib or dalpiciclib or drugs with a similar chemical structure or class.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: osimertinib in combination with dalpiciclib	Drug: Osimertinib plus Dalpiciclib; osimertinib 80mg daily plus dalpiciclib 125mg daily for 21 days followed by 7 days off in each 28-day treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
disease control rate (DCR)	12 months
Duration of Response (DoR)	12 months
Progression Free Survival (PFS)	12 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): December 15, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; CDK4/6 inhibitors; EGFR activating mutations; Third-generation EGFR-TKI; Cell cycle signaling pathway aberrations
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: DAL20240409

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No