Adagrasib vs Docetaxel for Non-Small Cell Lung Cancer

(KRYSTAL-12 Trial)

Recruiting at 787 trial locations

Overseen By Mirati Therapeutics Study Locator Services

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mirati Therapeutics Inc.

Must not be taking: KRAS G12C inhibitors

Disqualifiers: Active brain metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 106 weeks

453 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment, adagrasib, against an existing drug, docetaxel, to determine which is more effective for treating non-small cell lung cancer (NSCLC) with a specific genetic change (KRAS G12C mutation). The goal is to assess whether adagrasib better stops or slows the cancer after other treatments have been attempted. This study targets individuals previously treated for this type of lung cancer who could receive docetaxel. The trial aims to determine if adagrasib provides a superior treatment option for patients with this specific mutation. As a Phase 3 trial, it represents the final step before FDA approval, offering patients access to a potentially more effective treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have been treated with a KRAS G12C targeting agent before, you cannot participate.

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

Previous studies have shown that the drug adagrasib (MRTX849) is well tolerated by patients with non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. Research indicates that while some patients experienced side effects, most were manageable. Serious side effects related to the treatment occurred in about 47% of patients. Although this number might seem high, such side effects are common in cancer treatments.

Overall, the safety of adagrasib appears promising, and it is considered well tolerated for individuals with this specific type of lung cancer. These findings can help prospective clinical trial participants understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Adagrasib for treating non-small cell lung cancer because it offers a novel approach by specifically targeting the KRAS G12C mutation, a common driver of this cancer. Unlike traditional chemotherapy options like Docetaxel, which attack rapidly dividing cells non-specifically, Adagrasib works by directly inhibiting this mutated protein, potentially leading to more effective and targeted treatment. This precision can result in fewer side effects and a better quality of life for patients.

What evidence suggests that this trial's treatments could be effective for metastatic NSCLC with a KRAS G12C mutation?

Research has shown that adagrasib (MRTX849), one of the treatments in this trial, may help treat non-small cell lung cancer (NSCLC) with a KRAS G12C mutation. Studies have found that patients with this mutation experienced longer periods without cancer progression when treated with adagrasib. Specifically, one trial showed that adagrasib significantly extended the time patients lived without their cancer progressing compared to other treatments. Additionally, most patients tolerate adagrasib well. These findings suggest that adagrasib could be an effective treatment option for this specific type of lung cancer. This trial will compare adagrasib to docetaxel, another treatment option under study. ^{1 2 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 non-small cell lung cancer (NSCLC) that has a specific mutation called KRAS G12C. Participants must have tried chemotherapy with docetaxel, but their cancer still grew. They should be in decent physical shape (ECOG 0-2). People can't join if they've used other drugs targeting the KRAS G12C mutation, have active brain tumors, or received any other cancer treatments after docetaxel.

Inclusion Criteria

My lung cancer has a specific KRAS G12C mutation.

I am eligible to be treated with docetaxel.

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

I have been treated with a drug targeting KRAS G12C mutation.

I have active cancer spread to my brain.

I haven't taken any cancer treatment after my last docetaxel dose.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either MRTX849 (adagrasib) or docetaxel for the treatment of metastatic NSCLC with a KRAS G12C mutation

Up to approximately 106 weeks

Regular visits as per treatment cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 143 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• MRTX849 (Adagrasib)

Trial Overview The study compares MRTX849 (adagrasib), an experimental drug, to docetaxel, a standard chemotherapy drug. It's designed to see which one is better at controlling NSCLC in patients who already had treatment and whose tumor carries the KRAS G12C mutation.

How Is the Trial Designed?

Group I: MRTX849 Experimental Treatment 1 Intervention

Group II: Docetaxel Active Control 1 Intervention

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

In a study involving 25 patients with advanced non-small cell lung cancer and asymptomatic brain metastases, the combination of ramucirumab and docetaxel showed a median progression-free survival of 3.9 months and a median overall survival of 20.9 months, indicating potential efficacy for this patient group.

The treatment was generally well-tolerated, with no severe adverse events like intracranial hemorrhage reported, although 40% of patients experienced grade 3 or higher neutropenia, suggesting that while the combination is promising, further studies with larger sample sizes are necessary to fully assess safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab Plus Docetaxel for Patients with Non-small cell Lung Cancer with Brain Metastases: A Multicenter, Open-Label Single-Arm Phase II Trial. Tanimura, K., Uchino, J., Kimura, H., et al.[2023]

In a phase III trial, nivolumab significantly improved health-related quality of life (HRQoL) and disease-related symptoms compared to docetaxel in patients with advanced non-squamous non-small cell lung cancer, with improvements noted at multiple time points (weeks 12, 24, 30, and 42).

Patients receiving nivolumab experienced a longer time to first deterioration in HRQoL compared to those treated with docetaxel, indicating a more favorable safety profile and sustained symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Reck, M., Brahmer, J., Bennett, B., et al.[2019]

Docetaxel, when combined with other agents like cisplatin and gemcitabine, shows promising response rates (up to 53%) and median survival times (8 to 13 months) in patients with non-small-cell lung cancer, based on multiple phase I and II trials.

The combinations of docetaxel with other treatments have manageable adverse effects, making them a viable option for patients, with ongoing phase III trials to further evaluate their effectiveness in first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. Ornstein, DL., Nervi, AM., Rigas, JR.[2022]

In the JAVELIN Lung 200 trial, avelumab showed improved 2-year overall survival (OS) rates compared to docetaxel in patients with higher PD-L1 expression, with rates of 36.4% for those with ≥50% PD-L1 and 40.2% for those with ≥80% PD-L1, indicating potential efficacy in specific subgroups.

Despite the primary analysis showing no significant overall survival benefit for avelumab compared to docetaxel, the longer follow-up data suggests that avelumab may be more effective for patients with higher PD-L1 expression, with a median duration of response of 19.1 months compared to 5.7 months for docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial. Park, K., Özgüroğlu, M., Vansteenkiste, J., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204619

Adagrasib in Non–Small-Cell Lung Cancer Harboring a ... Table S2 includes efficacy outcomes for all 116 patients ... KRYSTAL-1: updated safety and efficacy data with adagrasib (MRTX849) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11534526/

Adagrasib in KRYSTAL-12 has Broken the KRASG12C ... The Phase III KRYSTAL-12 trial demonstrated that adagrasib significantly improved median progression-free survival (mPFS) compared with ...

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

KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in ... Conclusions: Adagrasib is well tolerated and demonstrates promising efficacy in pretreated patients with NSCLC harboring a KRASG12C mutation. A ...

4. news.bms.com news.bms.com/news/details/2024/KRAZATI-adagrasib-Demonstrated-Statistically-Significant-Improvement-in-Progression-Free-Survival-in-Patients-with-Pretreated-Locally-Advanced-or-Metastatic-KRASG12C-Mutated-Non-Small-Cell-Lung-Cancer/default.aspx

KRAZATI (adagrasib) Demonstrated Statistically Significant ... KRAZATI (adagrasib) Demonstrated Statistically Significant Improvement in Progression-Free Survival in Patients with Pretreated Locally Advanced ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10860949/

Safety and Intracranial Activity of Adagrasib in Patients With ... CNS metastases occur in 27%-42% of patients with non–small-cell lung cancer (NSCLC) that harbor KRASG12C mutations at diagnosis. Prognosis is ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00866-9/abstract

mutated non-small-cell lung cancer (KRYSTAL-12): a ... Grade 3 and above treatment-related adverse events occurred in 140 (47%) of 298 patients treated with adagrasib and 64 (46%) of 140 with ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT485936

First-line adagrasib (ADA) with pembrolizumab (PEMBRO) ... First-line ADA plus PEMBRO demonstrated promising clinical efficacy and a manageable safety profile, regardless of PD-L1 status.