Adagrasib + Nab-Sirolimus for Non-Small Cell Lung Cancer

No longer recruiting at 8 trial locations

Overseen By Mirati Therapeutics Study

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mirati Therapeutics Inc.

Disqualifiers: Intestinal disease, Lung disease, Cardiac abnormalities, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with non-small cell lung cancer (NSCLC) that has a specific genetic change called a KRAS G12C mutation. The study combines two drugs, adagrasib (also known as Krazati or MRTX-849) and nab-sirolimus (also known as Sirolimus albumin-bound nanoparticles, ABI-009, FYARRO, Nab-rapamycin, or TARZIFYX), to evaluate their safety and effectiveness in treating the cancer. The focus is on individuals whose cancer has spread or cannot be surgically removed and who have no other curative treatment options. Those aware of having this genetic mutation and meeting these conditions might be suitable for the trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that adagrasib, when used alone, is generally safe for patients with advanced solid tumors. In one study, patients took 600 mg of adagrasib twice a day, and it proved safe with some positive effects on tumors. Nab-sirolimus also has a strong safety record, particularly for certain tumors with genetic changes.

Both treatments have been tested separately, but their combined use is still under investigation. Direct data on the safety of this combination is not yet available, but ongoing research focuses on ensuring its safety for patients. This trial is in its early stages, primarily assessing safety and determining the correct dose. Since adagrasib and nab-sirolimus have been safe individually, researchers remain hopeful about their combined safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Adagrasib and nab-Sirolimus for non-small cell lung cancer because it targets the KRAS G12C mutation, which is a specific genetic alteration driving tumor growth. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Adagrasib specifically inhibits the abnormal KRAS protein, potentially leading to fewer side effects and more effective targeting of cancer cells. Additionally, nab-Sirolimus is a nanoparticle form of sirolimus, which enhances delivery and absorption in the body, potentially improving its efficacy against cancer cells. This combination approach offers a novel mechanism of action that could provide a more targeted and potentially more effective treatment option for patients with this mutation.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that adagrasib yields promising results in treating non-small cell lung cancer (NSCLC) with the KRAS G12C mutation. In earlier studies, adagrasib reached the brain and showed positive effects in patients with this type of lung cancer. In this trial, participants will receive a combination of adagrasib and nab-sirolimus. This combination aims to attack cancer cells more effectively by targeting multiple pathways of cancer growth. Although these findings are still early, they suggest that this treatment could offer new hope for patients with advanced NSCLC. ^{1 2 3 5 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or non-small cell lung cancer (NSCLC) that have a specific genetic change called KRAS G12C mutation. They should not be candidates for surgery to remove the tumor and must not have any other curative treatment options available. Their body's major functions need to be stable, and they must have measurable signs of cancer according to certain medical criteria.

Inclusion Criteria

Measurable disease per RECIST 1.1.

My cancer has a KRAS G12C mutation.

My cancer cannot be removed by surgery or has spread.

Exclusion Criteria

I have heart problems.

I have a history of serious gut issues that could affect medication absorption.

I have had lung conditions needing steroids or currently have active lung issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Dose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy in patients with solid tumors

30 months

Phase 2: Treatment

Evaluate the safety, tolerability, and clinical activity of adagrasib in combination with nab-sirolimus in patients with NSCLC

30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adagrasib
• nab-Sirolimus

Trial Overview The study is testing a combination of two drugs: Adagrasib and nab-Sirolimus, in patients with advanced cancers that carry the KRAS G12C mutation. It aims to find out the safest dose levels, how the body processes these drugs, and their effectiveness against these types of cancers.

How Is the Trial Designed?

Group I: Dose Escalation and Clinical Efficacy Experimental Treatment 2 Interventions

Dose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy of adagrasib in combination with nab-sirolimus in patients with solid tumors (Phase 1) and NSCLC (Phase 2) harboring a KRAS G12C mutation

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

Approved in United States as Krazati for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
• KRAS G12C-mutated locally advanced or metastatic colorectal cancer

Approved in European Union as Krazati for:

• KRAS G12C mutation non-small cell lung cancer

Who Is Running the Clinical Trial?

Mirati Therapeutics Inc.

Lead Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Aadi Bioscience, Inc.

Industry Sponsor

Trials

18

Recruited

580+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05840510?term=AREA%5BInterventionSearch%5D(FYARRO)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=6

Study Details | NCT05840510 | Adagrasib in Combination ... This study will evaluate the safety and tolerability and clinical activity of adagrasib in combination with nab-sirolimus in patients with advanced solid tumors ...

2. aadibio.com aadibio.com/aadi-bioscience-recieves-fda-orphan-product-development-grant-for-treatment-of-advanced-pecoma-2-2-2-2/

Aadi Bioscience Breakthrough Therapy nab-Sirolimus (ABI ... Exploratory mutational analysis shows an 89% confirmed response rate in TSC2 mutated tumors; US FDA New Drug Application expected to be ...

3. prnewswire.com prnewswire.com/news-releases/mirati-therapeutics-and-aadi-bioscience-partner-to-evaluate-the-combination-of-adagrasib-with-nab-sirolimus-in-patients-with-advanced-non-small-cell-lung-cancer-and-other-solid-tumors-with-a-krasg12c-mutation-301646795.html

Mirati Therapeutics and Aadi Bioscience Partner to ... Adagrasib has also shown, in clinical trials, CNS penetrance and single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04685135

NCT04685135 | Phase 3 Study of MRTX849 (Adagrasib) ... This Phase 3 study will evaluate the efficacy of the investigational agent MRTX849 (adagrasib) versus docetaxel in patients who have been previously treated ...

5. aadibio.com aadibio.com/wp-content/uploads/2023/04/AACR-Preclinical-Poster.pdf

Synergistic Antitumor Activity of nab-Sirolimus in ... KRAS is frequently mutated in non-small cell lung cancer (NSCLC) and other tumor types, with KRAS G12C mutation representing ~12% of patients with NSCLC1.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35167329/

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib ... Adagrasib 600 mg twice a day was well tolerated and exhibited antitumor activity in patients with advanced solid tumors harboring the KRAS ...