JDQ443 vs Docetaxel for Non-Small Cell Lung Cancer

(KontRASt-02 Trial)

Not currently recruiting at 157 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments for individuals with advanced non-small cell lung cancer (NSCLC) who have a specific KRAS G12C mutation. It evaluates the new drug JDQ443 (Opnurasib) against the standard treatment, docetaxel, to determine which is more effective. Candidates who have previously undergone platinum-based chemotherapy and an immune checkpoint inhibitor may be suitable. Participants should not have certain other mutations or active brain metastases. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Earlier studies have found JDQ443 to be safe and tolerable for people with non-small cell lung cancer (NSCLC) who have a KRAS G12C mutation. Most participants taking 200 mg of JDQ443 twice a day managed the treatment well.

Some side effects occurred, but they were mostly mild to moderate. While some participants experienced discomfort, the symptoms were not severe enough to stop the treatment. It is important to note that JDQ443 is still under study, and further research will provide a better understanding of its safety.

In summary, JDQ443 appears reasonably safe for treating NSCLC with this specific mutation based on current studies. Prospective trial participants may find this information helpful in understanding what to expect regarding the safety of JDQ443. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about JDQ443 because, unlike many current treatments for non-small cell lung cancer that target general cancer growth, JDQ443 specifically targets a mutation in the KRAS gene, which is a common driver of this cancer type. This targeted approach may lead to more effective treatment outcomes with potentially fewer side effects. By honing in on this specific mutation, JDQ443 promises to provide a more personalized and precise treatment option compared to traditional chemotherapy like docetaxel.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that JDQ443, one of the treatments in this trial, may help treat non-small cell lung cancer (NSCLC) with a specific KRAS gene change called G12C. Studies have found that JDQ443 works well and is generally safe for patients. In one study, patients with this gene change responded well, indicating that JDQ443 can effectively target and control the cancer. Patients in previous trials experienced manageable side effects with JDQ443, suggesting it is a promising option for those who have tried other treatments. Participants in this trial will receive either JDQ443 or Docetaxel, a standard treatment option for NSCLC. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05445843

NCT05445843 | Study of Efficacy and Safety of JDQ443 ... This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or ...

2. tandfonline.com tandfonline.com/doi/full/10.1080/14656566.2025.2536352?src=

Profiling opnurasib (JDQ-443) for the treatment of non- ... Response rates and survival outcomes are lower compared to other targeted therapies in NSCLC ... non-small cell lung cancer (NSCLC). Oral presentation. In: ASCO ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9007

Safety and efficacy of JDQ443 in KRAS G12C-mutated ... JDQ443 demonstrates an acceptable safety and tolerability profile at 200 mg BID, with clinical activity in pts with NSCLC.

4. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(24)00198-0/fulltext

A Phase II Study of Neoadjuvant Opnurasib KRAS G12C ... A Phase II study of neoadjuvant opnurasib KRAS G12C inhibitor in patients with surgically resectable non-small cell lung cancer (CCTG IND.242A)

5. ncoda.org ncoda.org/wp-content/uploads/2025/05/KontRASt-01-update-Safety-and-Efficacy-of-JDQ443-in-KRAS-G12C-mutated-solid-tumors-including-non-small-cell-lung-cancer-NSCLC-.pdf

Safety and efficacy of JDQ443 in KRAS G12C-mutated ... ... data are plotted out of n = 27 patients with NSCLC who received ... CRC, colorectal cancer; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04699188

NCT04699188 | Study of JDQ443 in Patients With ... This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination ...