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Advanced Lung Non-Small Cell CarcinomaPhase 1NCT05166616

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

A Phase 1 study testing Biopsy, Osimertinib and Triptolide Analog in people with Advanced Lung Non-Small Cell Carcinoma and Locally Advanced Lung Non-Small Cell Carcinoma, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Osimertinib and Triptolide Analog
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
7 Mar 2022to 28 Oct 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%
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  • 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
  • Hemoglobin >= 9 g/dL (within 14 days prior to day 1 of protocol therapy)
  • Total bilirubin =< 1.5 X ULN (unless has Gilbert's disease). Total bilirubin < 3 x ULN in the presence of documented Gilbert's disease (within 14 days prior to day 1 of protocol therapy)
  • Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) (if liver metastases are present, then =< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN if liver metastases are present, then =< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
  • Alkaline phosphatase =< 2.5 x ULN if liver metastases are present, then =< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
  • Serum creatinine within normal limits, OR creatinine clearance of >= 60 mL/min per 24 hour urine test for patients with creatinine levels above ULN (within 14 days prior to day 1 of protocol therapy)
  • Creatinine clearance (CrCl, by Cockcroft-Gault) is utilized for all patients to allow for evaluation of the effect of CrCl on the minnelide/triptolide exposures
  • If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
  • If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  • If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
  • If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  • Albumin >= 3.0 /dL (within 14 days prior to day 1 of protocol therapy)
  • Urinalysis - no clinically significant abnormalities (within 14 days prior to day 1 of protocol therapy)
  • QT corrected (QTc) =< 470 ms (using the Bazett's formula)
  • Note: To be performed within 28 days prior to Day 1 of protocol therapy.
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 weeks after the last dose of protocol therapy. Contraception must be continued following discontinuation of the study drugs for at least five half-lives of both study drugs
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • Female patients of childbearing potential must:
  • Agree to practice 1 highly effective method of non-hormonal contraception and one additional effective (barrier) method at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
  • Agree to practice true abstinence, when is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Agree not to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug. Agree not to breast-feed for the duration of treatment through 6 months post treatment.
  • Male patients of childbearing potential must:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug.
  • Patients must be able to swallow and retain oral medications
  • Previously tolerant of osimertinib at 80 mg QD

Who cannot join

  • Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 21 days prior to day 1 of protocol therapy (6 weeks for nitrosoureas or Mitomycin C). Exceptions to this exclusion are brain radiation and osimertinib
  • 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
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  • 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
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Diagnosis of congenital long QT syndrome
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 1b Open-Label, Dose-Escalation, Safety, and Pharmacodynamic Study of Minnelide™ Capsules Given in Combination With Osimertinib in Patients With EGFR Mutated NSCLC

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of triptolide analog (minnelide) capsules when given in combination with osimertinib.

II. To establish the dose of minnelide capsules recommended for future phase II studies when given in combination with full dose osimertinib (recommended phase II dose [RP2D]).

SECONDARY OBJECTIVES:

  1. To observe patients for any evidence of antitumor activity of minnelide capsules by objective radiographic assessment when in combination with osimertinib.

II. To determine pharmacodynamic effects of minnelide capsules on heat shock protein (HSP)72 levels when given in combination with osimertinib.

EXPLORATORY OBJECTIVES:

  1. Measure HSP levels, pre/post and during therapy as predictive biomarker. II. Determine levels of minnelide in the blood, and its effect. III. Determine the cell free deoxyribonucleic acid (DNA) in blood as biomarker. IV. Evaluate the microbiome pre-, during-, and post-therapy as potentiator of therapeutic response.
  2. Determine the exosomes as biomarker.

OUTLINE: This is a dose-escalation study of minnelide.

Patients receive minnelide orally (PO) once daily (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.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Being tested
Biopsy, Osimertinib, Triptolide Analog
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Correlative studies

  • OsimertinibDrug

    Also called AZD-9291, AZD9291, Mereletinib, Tagrisso

    Given PO

  • Triptolide AnalogDrug

    Also called Minnelide

    Given PO

Study groups in NCT05166616
Study groupRoleWhat they receive
Treatment (minnelide, osimertinib)ExperimentalPatients 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.
Receives: Procedure: Biopsy; Drug: Osimertinib; Drug: Triptolide Analog

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) of osimertinib and minnelide

    Measured: Up to 28 days

  2. Recommended phase II dose (RP2D) of minnelide and osimertinib

    Measured: Up to 28 days

Secondary outcomes (7)

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

    To analyze the pharmacodynamic effects of Minnelide on HSP72 protein levels in serum collected at specific timepoints before and after treatment.

    Measured: Up to 2 years

  2. Objective response rate

    Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

    Measured: Up to 2 years

  3. Duration of overall response

    Measured: Up to 2 years

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

    Assessed by objective radiographic assessment.

    Measured: Up to 2 years

  5. Incidence of adverse events

    Assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Up to 2 years

  6. Progression-free survival (PFS)

    Assessed per RECIST v 1.1. Median PFS will be determined using the Kaplan-Meier method.

    Measured: Up to 2 years

  7. Overall survival

    Assessed per RECIST v 1.1.

    Measured: From the date of study enrollment to the date of death from any cause, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2021
  2. Study start7 Mar 2022
  3. Primary completion28 Oct 2027 (estimated)
  4. Study completion28 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05166616
Sponsor's protocol ID
20609
Other IDs
NCI-2021-12558, 20609, P30CA033572
Status last verified
Mar 2026
First submitted
29 Nov 2021
Last updated
5 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Osimertinib and Triptolide Analog in people with Advanced Lung Non-Small Cell Carcinoma and Locally Advanced Lung Non-Small Cell Carcinoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of osimertinib and minnelide (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05166616.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.

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