Adagrasib vs Docetaxel for Non-Small Cell Lung Cancer

(KRYSTAL-12 Trial)

Recruiting at 711 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

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called adagrasib against an existing chemotherapy drug, docetaxel. It focuses on patients with advanced lung cancer who have a specific genetic mutation (KRAS G12C) and have already had treatment. The new drug aims to block this mutation in cancer cells to stop their growth.

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.

What data supports the effectiveness of the drug Adagrasib vs Docetaxel for Non-Small Cell Lung Cancer?

Research shows that docetaxel, when combined with other treatments like ramucirumab, has been effective in treating non-small cell lung cancer, suggesting its potential effectiveness in combination with other drugs like Adagrasib. ^{1 2 3 4 5}

Is docetaxel safe for treating non-small cell lung cancer?

Docetaxel has been used in various studies for non-small cell lung cancer and is generally considered safe, but it can cause side effects like febrile neutropenia (a condition where you have a fever and low white blood cell count). ^{1 5 6 7 8}

What makes the drug Adagrasib unique for treating non-small cell lung cancer?

Adagrasib (MRTX849) is unique because it specifically targets a mutation in the KRAS gene, which is a common driver of cancer growth in non-small cell lung cancer, offering a more targeted approach compared to traditional chemotherapy like docetaxel. ^{4 8 9 10 11}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of ramucirumab and docetaxel: a single-arm, prospective, multicenter, non-interventional, observational, post-marketing safety study of NSCLC in Japan. [2023]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer: a systematic review and meta-analysis of randomised clinical trials. [2022]

5. England 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. [2023]

6. England 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. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Real-World Efficacy of Nintedanib Plus Docetaxel After Progression on Immune Checkpoint Inhibitors: Results From the Ongoing, Non-interventional VARGADO Study. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Administration of docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte colony-stimulating factor for pretreated non-small cell lung cancer: a phase II study. [2023]

9. England 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. [2022]

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

Docetaxel (Taxotere) and neoadjuvant chemotherapy for non-small cell lung cancer. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Docetaxel: meeting the challenge of non-small cell lung cancer management. [2019]