MRTX849 for Cancer

Not currently recruiting at 392 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mirati Therapeutics Inc.

Disqualifiers: Intestinal disease, Major gastric surgery, Other active cancer

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

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 called MRTX849 (also known as Adagrasib or Krazati) for individuals with advanced solid tumors that have a specific KRAS G12C mutation. The researchers aim to determine the safety and effectiveness of MRTX849, both alone and in combination with other drugs like cetuximab and pembrolizumab. The trial includes different phases to identify the best dose and treatment combinations. It suits those with tumors that cannot be surgically removed or have spread, who have the KRAS G12C mutation, and for whom standard treatments are not an option. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 MRTX849, also known as adagrasib, is generally safe for patients with certain cancer mutations. In earlier studies, patients taking adagrasib alone experienced some side effects, but serious liver problems were rare, occurring in only 0.3% of patients. When combined with cetuximab, another cancer treatment, the combination remained manageable. Most side effects were mild to moderate, with pneumonia affecting about 4.3% of patients.

For the combination of adagrasib with pembrolizumab, a common cancer treatment, studies have shown similar safety to each drug used alone, with no new safety concerns. Information on adagrasib combined with afatinib is less detailed, as research is still in the early stages to better understand its safety.

Overall, these treatments remain under study, but early findings suggest they are manageable for most patients with careful monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MRTX849 because it offers a novel approach to targeting cancer, particularly for conditions like non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Most cancer therapies aim at a broad spectrum of cancer cells, but MRTX849 specifically targets KRAS G12C mutations, which are common in these types of cancer. This specific targeting could potentially lead to more effective treatments with fewer side effects compared to traditional chemotherapy. Additionally, MRTX849 is being explored in combination with other drugs like cetuximab, afatinib, and pembrolizumab, which may enhance its effectiveness and offer new hope for patients with limited treatment options.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors with a KRAS G12C mutation?

Previous studies have shown that MRTX849 (adagrasib) holds promise for treating cancers with the KRAS G12C mutation. In this trial, participants with non-small cell lung cancer (NSCLC) may receive MRTX849 alone or with other drugs. Specifically, 42% of NSCLC patients experienced a partial response, with tumors shrinking, and some responses lasted six months or more. Participants with colorectal cancer (CRC) in this trial may receive MRTX849 combined with cetuximab. Earlier studies reported a 34% overall response rate for this combination, indicating tumor reduction or disappearance. For pancreatic cancer, about 37% of patients saw tumor shrinkage, and over 80% had their disease under control. These findings suggest that MRTX849 could effectively treat cancers with this specific mutation. ^{6 7 8 9 10}

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 a specific mutation called KRAS G12C. They should have tried all standard treatments without success or declined them, and their cancer must be inoperable or spread to other parts of the body. People can't join if they have another active cancer, serious gut diseases, major stomach surgery history, trouble swallowing pills, or HER2 positive breast cancer.

Inclusion Criteria

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

I have NSCLC and either there's no standard treatment available or I've declined it.

My cancer has a KRAS G12C mutation.

Exclusion Criteria

I do not have any other active cancer.

I have been diagnosed with HER2 positive breast cancer.

I have had major stomach surgery or can't swallow pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Exploration

Dose escalation of MRTX849 to determine maximum tolerated dose

12 months

Regular visits for dose escalation and monitoring

Phase 1b Expansion

Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849

12 months

Regular visits for safety and pharmacokinetic assessments

Phase 2

Evaluation of clinical activity of MRTX849 in separate cohorts stratified by histological diagnosis, prior treatment history or co-mutation status

20 months

Regular visits for clinical activity evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRTX849

Trial Overview The study tests MRTX849 (adagrasib) to see how safe it is and how well patients tolerate it. It also looks at what the drug does inside the body and whether it works against cancers with the KRAS G12C mutation. Patients may also receive other drugs like Pembrolizumab, Afatinib, or Cetuximab as part of their treatment.

How Is the Trial Designed?

Group I: Pilot Phase 1b Combination with Pembrolizumab Experimental Treatment 2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC

Group II: Pilot Phase 1b Combination with Cetuximab in PDAC Experimental Treatment 2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)

Group III: Pilot Phase 1b Combination with Cetuximab in NSCLC Experimental Treatment 2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC

Group IV: Pilot Phase 1b Combination with Cetuximab Experimental Treatment 2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Group V: Pilot Phase 1b Combination with Afatinib Experimental Treatment 2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC

Group VI: Phase 2 Combination with Cetuximab Experimental Treatment 2 Interventions

Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Group VII: Phase 2 Experimental Treatment 1 Intervention

Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849

Group VIII: Phase 1b Expansion Experimental Treatment 1 Intervention

Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens

Group IX: Phase 1 Dose Exploration Experimental Treatment 1 Intervention

Dose escalation of MRTX849 to determine maximum tolerated dose

MRTX849 is already approved in United States, European Union for the following indications:

Approved in United States as Krazati for:

• Locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations
• Locally advanced or metastatic colorectal cancer with KRAS G12C mutations

Approved in European Union as Krazati for:

• Non-small cell lung cancer with KRAS G12C mutations

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

Avapritinib is a targeted protein kinase inhibitor that has shown a remarkable overall response rate of 95% in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the PDGFRA D842V mutation, with a median duration of response of 22.1 months.

While avapritinib is effective, it is associated with common side effects such as nausea, fatigue, and mild cognitive impairment, as well as rarer but serious events like severe encephalopathy and bleeding, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA assessment of avapritinib in the treatment of gastrointestinal stromal tumours harbouring the PDGFRA D842V mutation. Trullas-Jimeno, A., Delgado, J., Garcia-Ochoa, B., et al.[2021]

Avapritinib is a selective tyrosine kinase inhibitor specifically targeting PDGFRA and KIT mutations, and it has been approved in the USA for treating gastrointestinal stromal tumors (GIST) with PDGFRA exon 18 mutations, including the D842V variant.

The drug is currently under regulatory review in the USA as a 4th-line treatment for GIST and is also being evaluated in the EU for the same indication, highlighting its potential as a significant treatment option for patients with advanced GIST.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avapritinib: First Approval. Dhillon, S.[2021]

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]

Avapritinib, a novel inhibitor targeting PDGFRA D842V mutations, demonstrated a manageable safety profile with no treatment-related deaths and a maximum tolerated dose of 400 mg in a study involving 82 patients with advanced gastrointestinal stromal tumors.

In patients specifically with PDGFRA D842V mutations, avapritinib showed significant antitumor activity, with 88% of patients achieving an overall response, including 9% complete responses and 79% partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Heinrich, MC., Jones, RL., von Mehren, M., et al.[2020]

ASP8374 is a fully human monoclonal antibody that effectively blocks the TIGIT immune checkpoint, leading to increased production of interferon (IFN)-γ and enhanced T-cell activation, especially when combined with pembrolizumab, an anti-PD-1 antibody.

In mouse tumor models, ASP8374 demonstrated anti-tumor efficacy both alone and in combination with anti-PD-L1 or anti-PD-1 antibodies, suggesting its potential as a therapeutic option for advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of ASP8374, a fully-human, antagonistic anti-TIGIT monoclonal antibody. Shirasuna, K., Koelsch, G., Seidel-Dugan, C., 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]

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]

Avapritinib, a selective kinase inhibitor, was well tolerated in a study of 59 Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST), with a recommended dose of 300 mg once daily and no dose-limiting toxicities reported.

The drug demonstrated significant anti-tumor activity, particularly in patients with PDGFRA D842V mutations, achieving an objective response rate of 75% and a clinical benefit rate of 86%, while also showing notable efficacy in patients receiving it as a fourth-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study. Li, J., Zhang, X., Deng, Y., et al.[2023]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2212419

Adagrasib with or without Cetuximab in Colorectal Cancer ... In addition, adagrasib monotherapy was associated with a median progression-free survival of 5.6 months and median overall survival of 19.8 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38587856/

Efficacy and Safety of Adagrasib plus Cetuximab in ... - PubMed Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20648

Clinical outcomes and safety profile of adagrasib in KRAS ... Adagrasib showed a median overall survival (OS) of 14.74 months (95% CI: 12.06–17.42, I² = 40.4%) and progression-free survival (PFS) of 6.80 ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)01315-6/fulltext

P-71 KRYSTAL-10: A randomized phase 3 study ... A randomized phase 3 study of adagrasib (MRTX849) in combination with cetuximab vs chemotherapy in patients with previously treated advanced colorectal cancer ...

5. onclive.com onclive.com/view/adagrasib-cetuximab-maintains-efficacy-in-kras-g12c-mutated-advanced-mcrc

Adagrasib/Cetuximab Maintains Efficacy in KRAS G12C– ... Adagrasib plus cetuximab shows sustained efficacy in KRAS G12C-mutant mCRC with a 34% ORR per BICR and 43% per investigator review. The disease ...

6. krazatihcp.com krazatihcp.com/nsclc/safety

Safety | KRAZATI® (adagrasib) for NSCLC View safety profile of KRAZATI® (adagrasib) for KRAS G12C-mutated NSCLC, including adverse reactions. Please see indications and important safety ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/216340Orig1s000Corrected_lbl.pdf

KRAZATI (adagrasib) tablets - accessdata.fda.gov In the pooled safety population of 366 patients [see Adverse Reactions (6.1)], drug-induced liver injury was reported in 0.3% of patients, ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9002

KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in ... Adagrasib is well tolerated and demonstrates promising efficacy in pretreated patients with NSCLC harboring a KRAS G12C mutation.

9. caymanchem.com caymanchem.com/product/31440/mrtx-849?srsltid=AfmBOopeqf6cAdjLBgrvz7yDNwHe1QUKE7Iki1y4_8IsRcMaIMXIIO3B

MRTX-849 (​Adagrasib, CAS Number: 2326521-71-3) MRTX-849. Item No. 31440. MRTX-849 (​Adagrasib, CAS Number: 2326521-71-3). Download Product Insert (PDF)Download Safety Data Sheet (SDS) (PDF). 1 mg: $44: In ...

10. bmsaccesssupport.com bmsaccesssupport.com/krazati/indications-important-safety-information

KRAZATI® (adagrasib)| Indication and Important Safety ... KRAZATI, as a single-agent, is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer ( ...