Minnelide + Osimertinib for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Osimertinib

Must not be taking: CYP3A4 inducers, Antiarrhythmics, Herbal meds

Disqualifiers: HIV, Hepatitis B/C, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination, minnelide (a triptolide prodrug) and osimertinib, for advanced non-small cell lung cancer. The goal is to determine the optimal dose and assess how these drugs work together, as they may be more effective in combination, particularly for patients with an EGFR mutation. It suits individuals whose lung cancer has spread, have EGFR mutations, and have experienced cancer progression despite osimertinib treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting, including strong CYP3A4 inducers/inhibitors, some antiarrhythmic agents, herbal and alternative medications, and specific drugs like clarithromycin, loperamide, and ondansetron. If you're taking any of these, you may need to stop them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that minnelide and osimertinib are being tested together to treat advanced lung cancer. The FDA has already approved osimertinib for treating lung cancer with certain mutations, indicating its general safety for patients with this type of cancer.

For minnelide, early studies in other cancer types have identified a safe dose and schedule. It has been tested in patients with stomach and intestinal cancers, which supports its safety for a broader patient group.

Although this combination is still under study, existing research on each drug provides some confidence in their safety. Trial participants will contribute to gathering more information about how these drugs work together. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lung cancer?

Researchers are excited about Minnelide and Osimertinib for lung cancer because these drugs offer a fresh approach compared to standard treatments like chemotherapy and radiation. Minnelide is derived from a natural compound called triptolide and works by disrupting cancer cell machinery, which is different from traditional methods that directly kill cells. Osimertinib, on the other hand, specifically targets mutations in the EGFR gene, which are common in lung cancer, offering a more personalized treatment strategy. Together, these drugs have the potential to provide a more effective and targeted attack on cancer cells with possibly fewer side effects.

What evidence suggests that minnelide and osimertinib might be effective treatments for advanced non-small cell lung cancer?

Research has shown that combining minnelide and osimertinib might help treat advanced non-small cell lung cancer with an EGFR mutation. In this trial, participants will receive both minnelide and osimertinib. Minnelide converts into an active substance called triptolide in the body, which has demonstrated strong anti-cancer effects in lab and animal studies, such as stopping tumors from spreading and extending survival. Osimertinib is already known to significantly delay cancer progression in patients with EGFR-positive lung cancer. Using these two treatments together is believed to enhance their individual effects, offering a hopeful option for patients with this specific type of lung cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Erminia Massarelli, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer that has spread and have specific EGFR gene mutations. They must have had tumor progression after standard osimertinib treatment, be able to swallow pills, not be pregnant or breastfeeding, use effective birth control, and agree to research biopsies. Excluded are those with certain heart conditions, active infections requiring systemic therapy, recent use of strong CYP3A4 inducers/inhibitors or antiarrhythmic agents.

Inclusion Criteria

My tumor has a specific EGFR mutation sensitive to certain treatments.

My liver function test is within the required range.

My blood clotting time is within the target range for my anticoagulant therapy.

Exclusion Criteria

I have not taken strong CYP3A4 drugs in the last 14 days.

I have a history of HIV or hepatitis B/C.

I have a serious health condition that is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive minnelide orally once daily on days 1-21 and osimertinib once daily on days 1-28. Cycles repeat every 28 days for 6 months.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months for 2 years.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Minnelide
• Osimertinib

Trial Overview

The trial is testing the combination of Minnelide (which turns into triptolide in the body) and Osimertinib for treating advanced lung cancer with EGFR mutations. It aims to find the best dose of Minnelide while checking how well it works alongside Osimertinib by blocking a protein needed for cancer cell growth.

How Is the Trial Designed?

Group I: Treatment (minnelide, osimertinib) Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study established an osimertinib-resistant cell line (HCC827/OSIR) from EGFR-sensitive HCC827 cells, demonstrating that these resistant cells have higher resistance to multiple EGFR tyrosine kinase inhibitors compared to the original cells.

Increased expression of IRE1α was identified as a potential mechanism for resistance to osimertinib, and targeting IRE1α with an inhibitor showed promise in reducing the number of viable resistant cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. Tang, ZH., Su, MX., Guo, X., et al.[2022]

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a study of 94 patients with advanced non-small-cell lung cancer (NSCLC) who had previously been treated, osimertinib showed a 47.3% overall objective response rate and a 90.1% disease control rate, indicating its effectiveness in this population.

Patients with the T790M mutation experienced significantly longer progression-free survival (PFS) compared to those without the mutation, highlighting osimertinib's targeted efficacy, especially in those with specific genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. Mu, Y., Xing, P., Hao, X., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, was effective for 2.5 years in a 78-year-old woman with T790M-positive lung cancer, but she eventually experienced disease progression due to the emergence of a new resistance mutation (C797G).

The case highlights the potential of liquid biopsy and next-generation sequencing to monitor clonal evolution and identify novel resistance mechanisms in patients treated with osimertinib, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. DE Carlo, E., Schiappacassi, M., Pelizzari, G., et al.[2022]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

Citations

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Minnelide and osimertinib may work better in treating patients with EGFR mutant advanced non-small cell lung cancer. Detailed Description. PRIMARY OBJECTIVES: I ...

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A general description of the clinical trial arm. It identifies the role of the intervention that participants receive. Types of arms include experimental arm, ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0753332224014677

Potential antitumor activity of triptolide and its derivatives

Minnelide exhibits potent anti-proliferative activity in vitro and in vivo, prevents tumor metastasis, and improves animal survival in preclinical models of ...

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pubmed.ncbi.nlm.nih.gov/38169017/

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This first-in-human, phase I clinical study identified a dose and schedule of Minnelide in patients with refractory GI cancers.

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theoncologynurse.com/lung-cancer-mm/osimertinib-nearly-doubles-pfs-receives-breakthrough-therapy-designation-in-frontline-treatment-of-egfr-positive-nsclc

Osimertinib Nearly Doubles PFS, Receives Breakthrough ...

Survival data were only 25% mature and OS had yet to be reached when lead investigator Suresh Ramalingam, MD, Deputy Director of the Winship Cancer Institute at ...

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astrazeneca-us.com/media/press-releases/2025/New-study-results-reinforce-TAGRISSO-osimertinib-as-the-backbone-therapy-for-EGFR-mutated-lung-cancer-across-stages-and-settings.html

New study results reinforce TAGRISSO® (osimertinib) as ...

In LAURA Phase III trial, TAGRISSO continues to demonstrate improved overall survival trend in unresectable, Stage III setting.