JDQ443 vs Docetaxel for Non-Small Cell Lung Cancer

(KontRASt-02 Trial)

Recruiting at 144 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Platinum-based chemotherapy, Immune checkpoint inhibitors

Must not be taking: Docetaxel, KRAS G12C inhibitors

Disqualifiers: EGFR mutation, ALK rearrangement, CNS 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

Compensation: Varies

Number of Visits: Unknown

96 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase III randomized open label study designed to compare JDQ443 as monotherapy to docetaxel in participants with advanced non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation who have been previously treated with a platinum-based chemotherapy and immune checkpoint inhibitor therapy either in sequence or in combination.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug docetaxel for non-small cell lung cancer?

Research shows that docetaxel is an active chemotherapy drug for advanced non-small cell lung cancer, providing symptom relief and maintaining quality of life in many patients, even after other treatments have failed. ^{1 2 3 4 5}

Is docetaxel generally safe for humans?

Docetaxel has been studied in many patients and is generally considered safe, but it can cause side effects like low white blood cell counts (neutropenia), fluid retention, and fatigue. People with liver problems may experience more severe side effects, and pre-treatment with steroids can help reduce some of these risks. ^{2 5 6 7 8}

What makes the drug JDQ443 unique for treating non-small cell lung cancer?

JDQ443 is a novel drug being compared to docetaxel, a well-established chemotherapy agent for non-small cell lung cancer, which works by stabilizing microtubules to prevent cancer cell division. JDQ443's unique mechanism or benefits over docetaxel are not detailed in the provided research, but its inclusion in a clinical trial suggests it may offer new advantages or reduced side effects. ^{7 9 10 11 12}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer that has a specific mutation (KRAS G12C) and who have already tried platinum-based chemo and immune therapy. They can't join if they've had certain lung conditions, other mutations like EGFR or ALK, active brain metastases, or previous treatment with docetaxel or KRAS G12C inhibitors.

Inclusion Criteria

You have at least one spot that can be measured or seen on a scan at the screening visit.

My cancer has a KRAS G12C mutation.

You have at least one spot that can be measured and evaluated by doctors.

Exclusion Criteria

I haven't had docetaxel or KRAS G12C inhibitors for advanced cancer, or if I did, my cancer didn't worsen within 12 months after treatment.

My cancer has EGFR mutation or ALK rearrangement.

I have cancer that has spread to my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants receive either JDQ443 or docetaxel as monotherapy

Approximately up to 24 months

Regular visits as per treatment protocol

Extension

Participants on docetaxel may cross-over to JDQ443 after progression

Approximately up to 33 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately up to 33 months

Treatment Details

Interventions

• Docetaxel
• JDQ443

Trial Overview The study compares JDQ443 alone to the chemotherapy drug docetaxel in patients whose lung cancer has worsened despite prior treatments. It's an open-label phase III trial where participants are randomly assigned to one of the two drugs.

Participant Groups

Group I: JDQ443 Experimental Treatment 1 Intervention

Participants will be treated with JDQ443

Group II: Docetaxel Active Control 1 Intervention

Participant will be treated with docetaxel following local guidelines as per standard of care and product labels

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

In a study of 27 patients with inoperable non-small-cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy, docetaxel showed a partial response rate of 24%, indicating its effectiveness as a treatment option.

The main side effect observed was severe neutropenia in 75% of patients, highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. Robinet, G., Thomas, P., Pérol, M., et al.[2018]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

In a phase 3 trial involving 423 patients with untreated stage IV or recurrent non-small-cell lung cancer (NSCLC) and PD-L1 expression of 5% or more, nivolumab did not show a significant improvement in progression-free survival compared to chemotherapy, with median times of 4.2 months versus 5.9 months, respectively.

Nivolumab demonstrated a better safety profile than chemotherapy, with 71% of patients experiencing treatment-related adverse events compared to 92% in the chemotherapy group, and significantly fewer severe adverse events (grade 3 or 4) at 18% versus 51%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. Carbone, DP., Reck, M., Paz-Ares, L., et al.[2022]

Docetaxel is a well-tolerated second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) that showed a partial response in 6.3% of patients and stable disease in 25%, with a median survival time of 8.1 months.

Importantly, treatment with docetaxel did not negatively affect the overall quality of life for patients, and it helped alleviate symptoms like shortness of breath and weight loss in many cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxetaxel in previously treated non-small cell lung cancer patients: clinical efficacy and quality of life. Sirisinha, T., Sirilertrakul, S., Jirajarus, M., et al.[2018]

Docetaxel is effective in treating non-small cell lung cancer (NSCLC) by promoting microtubule assembly, leading to cell cycle arrest and death, and has shown survival benefits in both first- and second-line treatments.

The primary toxicity associated with docetaxel is neutropenia, which can be managed with weekly dosing, while other side effects like peripheral edema and interstitial pneumonitis can be mitigated with premedication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the treatment of non-small cell lung carcinoma: an update and analysis. Gubens, MA., Wakelee, HA.[2020]

In a phase II study involving 41 chemotherapy-naive patients with advanced non-small-cell lung cancer, docetaxel showed significant efficacy, achieving a 33% partial response rate with a median response duration of 14 weeks.

The treatment was associated with notable toxicities, including severe neutropenia in 97% of patients, hypersensitivity reactions in 36%, and fluid retention in 54%, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. Fossella, FV., Lee, JS., Murphy, WK., et al.[2018]

In a study of 182 elderly patients (average age 76) with advanced non-small-cell lung cancer, docetaxel showed a significant improvement in progression-free survival (5.5 months) and response rates (22.7%) compared to vinorelbine (3.1 months and 9.9%, respectively).

While docetaxel did not significantly improve overall survival compared to vinorelbine, it was associated with better disease-related symptom improvement and was generally well tolerated, making it a potential option for standard treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). Kudoh, S., Takeda, K., Nakagawa, K., et al.[2022]

References

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

High-risk localized prostate cancer: integrating chemotherapy. [2018]

2. France pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. [2018]

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

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

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

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. [2022]

5. Thailand pubmed.ncbi.nlm.nih.gov

Doxetaxel in previously treated non-small cell lung cancer patients: clinical efficacy and quality of life. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Optimal use of docetaxel (Taxotere): maximizing its potential. [2018]

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

Docetaxel in the treatment of non-small cell lung carcinoma: an update and analysis. [2020]

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

Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. [2018]

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

Neoadjuvant chemotherapy with docetaxel in non--small cell lung cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the neo-adjuvant setting in non-small-cell lung cancer. [2020]

11. Uganda pubmed.ncbi.nlm.nih.gov

[Fatal acute interstitial lung disease associated with docetaxel administration: about a case and review of the literature]. [2018]

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

Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). [2022]