Sapanisertib + Osimertinib for Non-Small Cell Lung Cancer

Not currently recruiting at 4 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the side effects and optimal dose of combining two drugs, sapanisertib and osimertinib, for advanced non-small cell lung cancer. It focuses on patients whose cancer has a specific mutation (EGFR mutation) and has worsened after similar treatment. The researchers aim to determine if these drugs can effectively stop cancer cell growth. This trial may suit those with stage IV non-small cell lung cancer who have experienced disease progression after taking osimertinib. 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.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking certain medications, including strong inhibitors or inducers of specific liver enzymes (CYP3A4, CYP3A5, CYP2C19, CYP2C9) and proton pump inhibitors, at least three weeks before starting the study. You also cannot take systemic corticosteroids within one week before the first dose of the study drug.

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

Research shows that osimertinib is usually well-tolerated by patients with specific lung cancer mutations. Earlier studies have shown promising results regarding its safety, with patients reporting manageable side effects.

Past studies have examined sapanisertib both alone and with other drugs to determine the safest and most effective dose. Although detailed safety information on using sapanisertib and osimertinib together is limited, ongoing research is investigating their combined effects. Early trials like this primarily focus on understanding the safety and optimal dosing of treatments, making safety a key concern.

Overall, these treatments are still under study to ensure their safety and effectiveness when used together. Researchers closely monitor trial participants to manage any side effects.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of sapanisertib and osimertinib for non-small cell lung cancer because it targets the disease in a unique way. While standard treatments, like other tyrosine kinase inhibitors, typically focus on blocking specific growth signals in cancer cells, sapanisertib adds a new layer by inhibiting mTOR, a protein that helps cancer cells grow and survive. This dual approach could potentially overcome resistance that often develops with existing treatments, offering hope for more effective management of the disease. Additionally, utilizing both drugs together might enhance their overall efficacy, potentially leading to better outcomes for patients.

What evidence suggests that sapanisertib and osimertinib could be effective for non-small cell lung cancer?

Research has shown that osimertinib effectively treats non-small cell lung cancer, particularly when specific changes occur in the EGFR gene. It blocks certain proteins that promote cancer cell growth. Sapanisertib is believed to function similarly by inhibiting tumor cell growth. In this trial, participants will receive a combination of sapanisertib and osimertinib. Studies have found that this combination is safe and might enhance treatment effectiveness. Early trial results suggest this combination could slow cancer progression in patients who have previously used other EGFR-targeting treatments.12567

Who Is on the Research Team?

PA

Penelope A. Bradbury

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with stage IV non-small cell lung cancer that has specific EGFR mutations and worsened after treatment with an EGFR inhibitor. Participants must have good physical function, measurable disease, meet certain lab criteria, not be pregnant or breastfeeding, and able to consent. Those with serious illnesses, certain heart conditions, or taking drugs that interact badly with the trial medications cannot join.

Inclusion Criteria

I am mostly self-sufficient and can carry out daily activities.
Your blood test results must meet specific requirements for white blood cells, red blood cells, platelets, kidney function, liver function, blood sugar, and heart function.
My non-squamous NSCLC has a specific EGFR mutation.
See 7 more

Exclusion Criteria

Any serious intercurrent or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
Your heart's pumping ability is lower than it should be.
I have NSCLC and no other active cancers or high-risk relapse cancers.
See 12 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive sapanisertib and osimertinib to determine the safety and recommended phase II dose

28 days
Daily oral administration

Dose Expansion

Evaluate the safety and preliminary efficacy of the drug combination

28 days per cycle, repeated
Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days, then every 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Osimertinib
  • Sapanisertib
Trial Overview The study is testing the combination of two drugs: MLN0128 (TAK-228) and AZD9291 (Osimertinib), to find out their side effects together and the best doses for treating advanced lung cancer. The goal is to see if these drugs can block enzymes needed for cancer cells to grow.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (sapanisertib, osimertinib)Experimental Treatment4 Interventions

Osimertinib is already approved in United States, European Union for the following indications:

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Approved in United States as Tagrisso for:
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Approved in European Union as Tagrisso for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Citations

Clinical Trial: NCT04479306This phase Ib trial studies the best dose, safety, and effect of alisertib or sapanisertib, in combination with osimertinib, in treating ...
Testing the Combination of MLN0128 (TAK-228) and ...This phase I trial studies the side effects and best dose of sapanisertib when given together with osimertinib in treating patients with stage IV EGFR ...
A phase II trial of mTORC1/2 inhibition in STK11 deficient non ...Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial ...
Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent ...Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ziv-aflibercept may stop the growth of solid tumors by ...
Results of a phase 1b study of osimertinib plus ...Here, we investigated the safety and efficacy of the aurora kinase inhibitor alisertib and the mTOR inhibitor sapanisertib in combination with osimertinib.
Osimertinib in Early-Stage EGFR-Mutated Non-small Cell ...Despite these challenges, osimertinib emerges as a promising and well-tolerated treatment option for patients with EGFR mutations in early-stage lung cancer.
Targeting NFE2L2/KEAP1 Mutations in Advanced NSCLC ...TAK-228 has single-agent activity in patients with NRF2-activated LUSC. This study reframes oncogenic alterations as biologically relevant based on their ...
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