MRTX0902 + MRTX849 for Solid Tumors

Recruiting at 35 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

228 Participants Needed

Trial Summary

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 the treatment MRTX0902 + MRTX849 safe for humans?

Adagrasib (MRTX849) is generally well tolerated in humans, with most side effects being mild to moderate, such as diarrhea, nausea, and fatigue. These side effects usually appear early in treatment and can be managed with medication and monitoring, leading to a low rate of treatment discontinuation. ^{1 2 3 4 5}

What makes the drug MRTX0902 + MRTX849 unique for treating solid tumors?

MRTX0902 + MRTX849 is unique because it targets specific genetic mutations in tumors, potentially offering a more personalized treatment approach compared to conventional chemotherapy, which is often ineffective for aggressive tumors like myxofibrosarcoma. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing a new drug, MRTX0902, alone and with another drug, adagrasib, in patients with advanced cancers that have specific genetic mutations. The goal is to see if these drugs are safe and can effectively block cancer growth signals. Adagrasib has shown promising results in treating certain types of advanced cancers.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

3. United States 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. [2023]

4. United States 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). [2023]

5. England 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Phase IB study of the mTOR inhibitor ridaforolimus with capecitabine. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma. [2021]

8. India pubmed.ncbi.nlm.nih.gov

Pazopanib in metastatic soft tissue sarcomas: Testing the waters in developing world. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

Establishment and characterization of NCC-MFS3-C1: a novel patient-derived cell line of myxofibrosarcoma. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

Establishment and characterization of NCC-MFS4-C1: a novel patient-derived cell line of myxofibrosarcoma. [2022]