MRTX0902 + MRTX849 for Solid Tumors

Not currently recruiting at 45 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mirati Therapeutics Inc.

Must not be taking: CYP3A substrates, P-gp inhibitors

Disqualifiers: Brain metastases, Hemoptysis, Pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, MRTX0902 and MRTX849 (also known as Adagrasib or Krazati), to evaluate their safety and effectiveness for people with advanced solid tumors that have specific gene mutations. The study aims to understand how the treatments work alone and together, focusing on tumors with KRAS mutations. People with solid tumors that have these specific mutations and whose disease cannot be treated with standard treatments might be suitable for the trial. Participants need measurable tumors and should not have complicating conditions like active brain issues or recent major surgeries.

As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatments work in people and measuring their effectiveness in an initial group, offering participants a chance to contribute to groundbreaking cancer research.

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

The trial requires that you stop taking medications that are substrates of CYP3A, strong inducers or inhibitors of CYP3A and/or P-gp, strong inhibitors of BRCP, and proton pump inhibitors. If you are on any of these medications, you will need to stop them before participating.

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

Earlier studies have shown that both MRTX0902 and MRTX849 (adagrasib) are safe for patients. Research indicates that MRTX0902 targets KRAS mutations, which are common in some cancers. Early results suggest it has a safety profile that patients can generally handle without severe side effects.

Studies on MRTX849 (adagrasib) have demonstrated it is well tolerated in people with various solid tumors. Participants in these studies reported manageable side effects, and the treatment effectively shrank tumors while keeping side effects in check.

Although the current trial is in its early stages, these previous findings provide reassurance about the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MRTX0902 and MRTX849 because they target the KRAS G12C mutation, which is a common driver in various solid tumors like non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Unlike standard treatments that may not specifically address this mutation, these drugs aim directly at inhibiting KRAS G12C, potentially offering a more precise and effective approach. This targeted action could lead to better outcomes and fewer side effects compared to broader treatments like chemotherapy. Additionally, the combination of MRTX0902 with adagrasib (MRTX849) might enhance the overall treatment efficacy against these specific cancer types.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research shows that combining MRTX0902 and MRTX849 (adagrasib) can effectively fight tumors. In this trial, some participants will receive this combination, which studies have found more powerful than using either treatment alone. Adagrasib showed positive results in patients with solid tumors that have a specific mutation called KRAS G12C, which is usually hard to treat. Previous studies indicated that adagrasib was both safe and effective in these patients. These treatments work by disrupting signals in cancer cells, helping to stop tumor growth. Overall, early research suggests they could benefit people with these difficult-to-treat cancers. ^{1 4 6 7 8}

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 that have specific mutations in the KRAS-MAPK pathway, who can't be cured by other treatments or choose not to undergo them. Participants must have a tumor that can be biopsied, measurable disease, good organ function, and an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory).

Inclusion Criteria

My tumor can be biopsied for study purposes.

My cancer cannot be removed by surgery or has spread to other parts of my body.

I have no curative treatment options left or available to me.

Exclusion Criteria

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

I have not had major surgery in the last 4 weeks.

I have had pneumonitis or lung disease affecting the tissue and space around the air sacs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1/1B Monotherapy

Dose escalation and evaluation of MRTX0902 monotherapy

8-12 weeks

Phase 1/1B Combination Therapy

Dose escalation and evaluation of MRTX0902 in combination with adagrasib, including food effect assessment

8-12 weeks

Phase 2

Evaluation of clinical activity and efficacy of MRTX0902 in combination with adagrasib in separate cohorts

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRTX0902
• MRTX849

Trial Overview

The study tests MRTX0902 alone and combined with MRTX849 (adagrasib) on patients with certain genetic changes in their tumors. It's an early-stage trial to check how safe these drugs are, how the body processes them, and if they work against cancer.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 2 Interventions

MRTX0902 and adagrasib combination RP2D administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12C mutation to include the following: NSCLC, CRC, Other Solid Tumors

Group II: Phase 1/1B Monotherapy Experimental Treatment 1 Intervention

Dose Escalation/Evaluation

Group III: Phase 1/1B Combination Therapy Experimental Treatment 2 Interventions

Dose Escalation/Evaluation and Food Effect Assessment

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

Published Research Related to This Trial

Adagrasib (MRTX849) is a KRASG12C inhibitor that has been administered to 853 patients with KRASG12C-mutated solid tumors, showing a favorable safety profile with mostly mild to moderate treatment-related adverse events (TRAEs) that are manageable and lead to low treatment discontinuation rates.

Common TRAEs include gastrointestinal issues and hepatic toxicities, which can be effectively managed through dose adjustments and supportive medications, highlighting the importance of clinician awareness and patient education for optimal treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Guidance for the Management of Adverse Events in Patients with KRASG12C-Mutated Non-Small Cell Lung Cancer Receiving Adagrasib. Zhang, J., Johnson, M., Barve, M., et al.[2023]

The combination of ridaforolimus (an mTOR inhibitor) and capecitabine showed good tolerability and feasibility in 32 adult patients, with defined recommended doses and manageable side effects like stomatitis and skin rash.

One patient experienced a partial response lasting 10 months, and 10 out of 29 evaluable patients had stable disease for at least 6 months, indicating potential antitumor activity that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IB study of the mTOR inhibitor ridaforolimus with capecitabine. Perotti, A., Locatelli, A., Sessa, C., et al.[2021]

A new myxofibrosarcoma (MFS) cell line, NCC-MFS3-C1, was established from a patient tumor, showing characteristics that reflect the aggressive nature of MFS, including constant proliferation and invasive behavior.

Drug screening revealed that the proteasome inhibitor bortezomib and the histone deacetylase inhibitor romidepsin effectively reduced the growth of NCC-MFS3-C1 cells, suggesting potential new treatment options for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and characterization of NCC-MFS3-C1: a novel patient-derived cell line of myxofibrosarcoma. Tsuchiya, R., Yoshimatsu, Y., Noguchi, R., et al.[2021]

A new myxofibrosarcoma (MFS) cell line, NCC-MFS4-C1, was established from a patient’s tumor, showing characteristics similar to the original tumor, which can help in understanding this aggressive cancer better.

Screening of a drug library revealed that several drugs, including actinomycin D and bortezomib, significantly reduced the proliferation of NCC-MFS4-C1 cells, suggesting potential new treatment options for MFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and characterization of NCC-MFS4-C1: a novel patient-derived cell line of myxofibrosarcoma. Yoshimatsu, Y., Noguchi, R., Tsuchiya, R., et al.[2022]

The KRYSTAL-1 study found that adagrasib (MRTX849), a KRASG12c inhibitor, is generally well tolerated by patients with non-small cell lung cancer, indicating a favorable safety profile.

Adagrasib demonstrated significant efficacy in treating non-small cell lung cancer with the KRASG12c mutation, and it also showed some activity in colorectal cancer and other solid tumors, although to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

In a study of 72 patients with metastatic soft tissue sarcoma in India, pazopanib showed a 24% partial response rate and a median overall survival of 11 months, indicating its efficacy as a treatment option.

Despite its effectiveness, 40% of patients required dose reductions, with a median tolerated dose of 600 mg daily, which is lower than the standard 800 mg dose, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib in metastatic soft tissue sarcomas: Testing the waters in developing world. Bajpai, J., Mullapally, SK., Kapoor, A., et al.[2022]

In a phase I/IB study involving 25 patients with advanced KRASG12C-mutant solid tumors, adagrasib (600 mg twice daily) demonstrated significant antitumor activity, with 53.3% of patients with non-small-cell lung cancer achieving a confirmed partial response after a median follow-up of 19.6 months.

Adagrasib was well tolerated, with the most common side effects being nausea (80%), diarrhea (70%), and fatigue (45%), indicating a manageable safety profile for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). Ou, SI., Jänne, PA., Leal, TA., et al.[2023]

A study of 64 high-grade myxofibrosarcoma samples identified integrin-α10 as a key gene linked to disease progression and poor outcomes, highlighting its potential as a therapeutic target.

Inhibition of the signaling pathway involving integrin-α10, TRIO, and RICTOR using specific drugs showed promising antitumor effects in both cell lines and mouse models, suggesting a new treatment strategy for high-risk myxofibrosarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma. Okada, T., Lee, AY., Qin, LX., et al.[2021]

Adagrasib (MRTX849) is a selective inhibitor targeting the KRASG12C mutation, which is common in non-small cell lung cancer (NSCLC) and linked to poor patient outcomes.

Recent Phase I/II studies have demonstrated that adagrasib shows promising efficacy and tolerability, marking a significant advancement in the treatment of KRASG12C-driven NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib. Brazel, D., Arter, Z., Nagasaka, M.[2022]

Adagrasib (MRTX849) is a promising treatment for patients with KRAS-mutant non-small cell lung cancer (NSCLC) and brain metastases, showing the ability to penetrate the central nervous system and achieve effective concentrations in cerebrospinal fluid.

In preclinical models and preliminary clinical data from two patients, adagrasib demonstrated tumor regression in brain metastases, indicating its potential efficacy in treating this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. Sabari, JK., Velcheti, V., Shimizu, K., et al.[2023]

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Oral administration of MRTX0902 in combination with MRTX849 results in a significant increase in antitumor activity relative to that of either ...

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NCT05578092 | A Phase 1/2 Study of MRTX0902 in Solid ...

This is a Phase 1/2, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX0902 alone and in combination ...

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ascopubs.org/doi/10.1200/JCO.2023.41.36_suppl.425082

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Adagrasib is well tolerated and demonstrates promising clinical activity in pretreated pts with PDAC, BTC, and other solid tumors harboring a KRAS G12C ...

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clinicaltrial.be/en/details/83167?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

A Phase 1/2 Study of MRTX0902 in Solid Tumors With ...

MRTX0902 and adagrasib combination therapy: KRAS G12C mutation. Unresectable or metastatic disease. No available treatment with curative intent; standard ...

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A Phase 1/2 Study of MRTX0902 in Solid Tumors With ...

This is a Phase 1/2, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX0902 alone and in ...

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Clinically, inhibitors that target KRAS G12C-mutant cancer have shown robust antitumor efficacy with tolerable safety profiles (25–28). KRAS G12C is the most ...

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A Phase 1/2 Study of MRTX0902 in Solid Tumors With ...

This is a Phase 1/2, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX0902 alone ...