Osimertinib and Abemaciclib in EGFR Mutant Non-Small Cell Lung Cancer After Osimertinib Resistance

NCT04545710 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 190752
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Lung cancer is the leading cause of cancer deaths. Advances in the systemic treatment of non-small cell lung cancer (NSCLC) have increased survival in metastatic EGFR-mutated NSCLC. However resistance to therapy can develop.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival at 6 months

  Rate of Progression Free Survival at 6 months on the combination.

  6 months

Study Arms (1)

Single Arm, POC

EXPERIMENTAL

Single arm, POC Safety and Efficacy Osimertinib 80 mg QD Abemaciclib 150mg BID

Drug: Abemaciclib; Drug: Osimertinib

Interventions

Abemaciclib DRUG

Abemaciclib 150mg BID

Also known as: Verzenios

Single Arm, POC

Osimertinib DRUG

Osimertinib 80mg daily

Also known as: Tagrisso

Single Arm, POC

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed NSCLC-lung adenocarcinoma histology.
• Tumor must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q).
• Patient must have Stage IV, recurrent or metastatic disease with EGFR mutant disease.
• Patient must have progressive disease on or after osimertinib (any number of prior treatment is allowed).
• At least one measurable lesion according to RECIST version 1.1
• Age \>18 years
• ECOG performance status ≤1
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
• Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
• The patient has adequate organ function for all of the following criteria, as defined below.
• Table 1: Laboratory Value Guidance to Establish Adequate Organ Function System Laboratory Value Hematologic ANC 1.5 × 109/L Platelets 100 × 109/L Hemoglobin 8 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Hepatic Total bilirubin 1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
• ALT and AST 3 × ULN Renal Serum creatinine 1.5 × ULN
• Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal.
• Negative urinary pregnancy test within 7 days prior to entry of study.

You may not qualify if:

• Chemotherapy or other investigational agent within three weeks prior to the start of study treatment.
• Radiotherapy within 4 weeks prior to randomization, except as follows:
• Palliative radiation to target organs other than chest or stereotactic radiotherapy to the chest may be allowed up to 2 weeks prior to treatment with osimertinib and abemaciclib.
• Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
• Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study.
• Known hypersensitivity to osimertinib or the excipients of any of the trial drugs.
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to study enrollment.
• Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 28 days after treatment has ended. \<Note: for osimertinib this must be 28 days, however this may be longer for other drugs.
• Female patients of childbearing potential who are nursing or are pregnant or are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and/or do not agree to submit to pregnancy testing required by this protocol.
• Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
• Known pre-existing interstitial lung disease (patients with previous radiation induced interstitial lung disease are allowed provided they do not require active treatment and symptoms attributed to interstitial lung disease have resolved).
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of osimertinib (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, and malabsorption).
• Active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
• QTcF \> 470 ms on average of 3 ECG recordings
• Leptomeningeal carcinomatosis.

Sponsors & Collaborators

• University of California, San Diego: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

abemaciclib; osimertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Hatim Husain, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 11, 2020
• Study Start: November 21, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)