Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer

NCT05166616 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 20609NCI-2021-12558P30CA033572
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the side effects and best dose of minnelide when given together with osimertinib for the treatment of non-small cell lung cancer that has spread to other places in the body (advanced) and has a change (mutation) in a gene called EGFR. Minnelide is a biologically inactive compound that can be broken down in the body to produce a drug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Minnelide and osimertinib may work better in treating patients with EGFR mutant advanced non-small cell lung cancer.

Conditions

Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma; Advanced Lung Non-Small Cell Carcinoma; Locally Advanced Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of osimertinib and minnelide

  Up to 28 days

• Recommended phase II dose (RP2D) of minnelide and osimertinib

  Up to 28 days

Secondary Outcomes (7)

• Pharmacodynamic effects of minnelide on heat shock protein (HSP)72 expression

  Up to 2 years

• Objective response rate

  Up to 2 years

• Duration of overall response

  Up to 2 years

• Evidence of anti-tumor activity of minnelide when in combination with osimertinib

  Up to 2 years

• Incidence of adverse events

  Up to 2 years

Other Outcomes (5)

• HSP levels pre and post therapy

  Baseline and up to 2 years

• Levels of minnelide in the blood

  Up to 2 years

• Cell free deoxyribonucleic acid (DNA) in blood

  Up to 2 years

Study Arms (1)

Treatment (minnelide, osimertinib)

EXPERIMENTAL

Patients receive minnelide PO QD on days 1-21 and osimertinib PO QD on days 1-28. Cycles repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.

Procedure: Biopsy; Drug: Osimertinib; Drug: Triptolide Analog

Interventions

Triptolide Analog DRUG

Given PO

Also known as: Minnelide

Treatment (minnelide, osimertinib)

Biopsy PROCEDURE

Correlative studies

Also known as: BIOPSY_TYPE, Bx

Treatment (minnelide, osimertinib)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Treatment (minnelide, osimertinib)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to two research biopsies
• If tumor is unbiopsiable or not safely biopsied, exceptions may be granted with study principal investigator (PI) approval
• Age: \>= 18 years
• Karnofsky performance \>= 70%
• Histologically confirmed advanced non-small cell lung cancer (NSCLC). Patients with locally advanced NSCLC must not be candidates for surgical resection, radiation, or chemoradiation with curative intent
• The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Tumor progression after receiving standard/approved osimertinib
• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy. Grade 2 neuropathy is allowed
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3 (within 14 days prior to day 1 of protocol therapy)
• NOTE: Growth factor is not permitted within 14 days of ANC assessment
• Platelets \>= 100,000/mm\^3 (within 14 days prior to day 1 of protocol therapy)
• NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment

You may not qualify if:

• Biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
• Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
• Patients receiving class 1A or class III antiarrhythmic agents within 14 days prior to Day 1 of protocol therapy
• Herbal and alternative (eg. turmeric, cannabidiol, ginseng) medications within 7 days prior to Day 1 of protocol therapy
• Clarithromycin, loperamide, ondansetron within 7 days prior to day 1 of protocol therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Active diarrhea
• Clinically significant uncontrolled illness
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score =\< 6 = Gleason Group 1) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry
• Females only: Pregnant or breastfeeding
• Any malabsorption condition
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
• Clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Biopsy; osimertinib; triptolide; 14-O-phosphonooxymethyltriptolide disodium salt

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Erminia Massarelli

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: December 22, 2021
• Study Start: March 7, 2022
• Primary Completion (Estimated): October 28, 2027
• Study Completion (Estimated): October 28, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)