JDQ443 for Non-Small Cell Lung Cancer

Not currently recruiting at 13 trial locations

Overseen By Pierre-Olivier Gaudreau

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Investigational drugs

Disqualifiers: Unresectable cancer, Cardiac disease, Infections, others

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

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 tests how a new treatment, JDQ443 (also known as Opnurasib), affects non-small cell lung cancer before surgery. The goal is to determine if this treatment can improve outcomes for patients with a surgically removable type of lung cancer. It is suitable for individuals diagnosed with this specific type of lung cancer within the past three months and who are preparing for surgery. Participants should not have received any previous cancer treatments for this condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other investigational drugs or anti-cancer therapy. It's best to discuss your specific medications with the trial team.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot be on other investigational drugs or anti-cancer therapy while participating in this trial.

Is there any evidence suggesting that JDQ443 is likely to be safe for humans?

Research has shown that JDQ443 is generally safe and well-tolerated. In earlier studies, patients with non-small cell lung cancer (NSCLC) who took 200 mg of JDQ443 twice daily experienced manageable side effects. Although some patients did encounter side effects, these were usually not severe enough to require stopping treatment. For those considering joining a trial with JDQ443, this safety information suggests that the treatment is likely tolerable for many participants. ^{1 2 3 4 5}

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

Unlike the standard treatments for non-small cell lung cancer, which typically include chemotherapy, targeted therapy, and immunotherapy, JDQ443 stands out because it is designed to act directly on specific mutations within cancer cells. JDQ443 targets the KRAS G12C mutation, a common and challenging mutation to treat in lung cancer. Researchers are excited about JDQ443 because it represents a new approach that could potentially lead to more effective and personalized treatment options for patients with this specific genetic profile, offering hope for better outcomes than current therapies.

What evidence suggests that JDQ443 might be an effective treatment for non-small cell lung cancer?

Studies have shown that JDQ443 can help treat non-small cell lung cancer (NSCLC), particularly in patients with a genetic change called KRAS G12C. Research indicates that JDQ443 is generally safe and well-tolerated, showing positive effects in treating NSCLC. In a group of patients with this cancer type, the treatment demonstrated promising results. In this trial, researchers are studying JDQ443 as a neoadjuvant therapy, meaning it is given before surgery. Although more studies are needed, early data appears encouraging for those considering this treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

Jonathan Spicer

Principal Investigator

McGill University, Montreal, QC Canada

Normand Blais

Principal Investigator

CHUM-Centre Hospitalier de l'Universite de Montreal, QC Canada

Are You a Good Fit for This Trial?

Adults with newly diagnosed non-small cell lung cancer (NSCLC) that can be removed by surgery are eligible. They should not have had previous cancer treatments, must be in good physical condition (ECOG 0 or 1), and have their major organs functioning well. Women and men who can have children must agree to use effective birth control. People with advanced, unresectable or metastatic cancer, serious medical conditions, certain heart diseases, or a history of significant allergies to similar drugs cannot participate.

Inclusion Criteria

My lung cancer diagnosis was confirmed by a lab test within the last 3 months.

My organ and bone marrow functions are currently healthy.

I am using a highly effective method of birth control.

Exclusion Criteria

I do not have serious heart rhythm problems or a family history of them.

You had another type of cancer before, but it's been treated and doesn't affect the safety or effectiveness of the new treatment being studied.

You have had a bone marrow, double umbilical cord blood, or solid organ transplant in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with JDQ443 to assess effects on lung cancer before surgery

6-8 weeks

Surgery

Participants undergo surgery to remove the tumor after neoadjuvant treatment

Adjuvant Treatment

Participants may receive standard of care adjuvant treatment followed by experimental adjuvant therapy with JDQ443 if MPR/cPR is achieved

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• JDQ443

Trial Overview The trial is testing JDQ443 as a new treatment for NSCLC before surgery. Participants will receive this medication within a specific timeframe prior to their planned surgical procedure aimed at completely removing the cancer. The study aims to evaluate how effective JDQ443 is when given before surgery in improving outcomes for patients.

How Is the Trial Designed?

Group I: Neoadjuvant therapy (JDQ443) followed by surgery. (ARM CLOSED) Experimental Treatment 1 Intervention

If \*MPR/cPR\* - standard of care adjuvant treatment may be followed by experimental adjuvant therapy (JDQ443) \*Major Pathological Response (MPR)/ Complete Pathological Response (cPR)

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Published Research Related to This Trial

In a phase 3 study involving 272 patients with advanced squamous-cell non-small-cell lung cancer, nivolumab significantly improved overall survival (9.2 months) compared to docetaxel (6.0 months), with a 41% lower risk of death.

Nivolumab also had a better safety profile, with only 7% of patients experiencing severe treatment-related adverse events, compared to 55% in the docetaxel group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. Brahmer, J., Reckamp, KL., Baas, P., et al.[2022]

Immune checkpoint inhibitors (ICIs) have shown promise in treating advanced non-small-cell lung cancer (NSCLC), but only a small number of patients experience significant and lasting benefits, highlighting the need for better patient selection.

Factors such as age, sex, performance status, smoking habits, and specific metastasis sites may influence the effectiveness of ICIs, suggesting that personalizing immunotherapy could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features affecting survival in metastatic NSCLC treated with immunotherapy: A critical review of published data. Passaro, A., Attili, I., Morganti, S., et al.[2020]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

A phase-Ib clinical trial is investigating the safety and efficacy of combining metformin with nivolumab, an immune checkpoint inhibitor, in patients with refractory solid tumors, including non-small-cell lung cancer and pancreatic cancer.

The trial aims to determine the optimal dose of metformin that enhances the effects of nivolumab, with a focus on safety and pharmacokinetics, enrolling a total of 39 to 48 patients across two parts of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Protocol: Phase-Ib Trial of Nivolumab Combined With Metformin for Refractory/Recurrent Solid Tumors. Kubo, T., Ninomiya, T., Hotta, K., et al.[2019]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

In a phase II trial involving 116 patients with squamous non-small-cell lung cancer, durvalumab demonstrated a 16% overall response rate and a disease control rate of 54%, indicating its potential effectiveness as a treatment after platinum-based chemotherapy.

The treatment was associated with a median overall survival of 11.6 months and a median progression-free survival of 2.9 months, with 32% of patients experiencing grade ≥ 3 treatment-related adverse events, suggesting that while durvalumab is active, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study). Borghaei, H., Redman, MW., Kelly, K., et al.[2022]

Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell lung cancer, based on a meta-analysis of 20 studies involving 3404 patients.

The presence of PD-L1 expression in patients is associated with a better response to nivolumab, indicating that PD-L1 status can help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. Zhao, B., Zhang, W., Yu, D., et al.[2019]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

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 four-year study of 80 patients with non-small cell lung cancer treated with anti-PD-1 and anti-PD-L1 therapies, significant overall survival rates were observed, particularly with nivolumab and pembrolizumab, showing 79.7% survival at 6 months and 100% at first-line treatment for pembrolizumab.

Adverse events were common, occurring in over 84% of patients, with fatigue and respiratory issues being the most reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of anti PD-1/PD-L1 antibodies as monotherapy in patients with non-small-cell lung cancer. Zayas-Soriano, M., Bonete-Sánchez, M., Campillo-López, J., et al.[2021]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

Monoclonal antibodies like nivolumab and pembrolizumab have shown significant efficacy in treating non-small cell lung cancer (NSCLC), with some patients experiencing durable responses lasting years after treatment.

Despite the success of these therapies, many NSCLC patients do not respond to anti-PD-1/PD-L1 treatments, highlighting the urgent need for biomarkers to identify which patients are likely to benefit from these immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? Grigg, C., Rizvi, NA.[2022]

For patients with nonsquamous non-small-cell lung cancer (NSCLC) who do not have specific oncogene mutations, new combination therapies involving pembrolizumab or atezolizumab with chemotherapy are now available, improving treatment options regardless of PD-L1 expression levels.

Second-line treatments are evolving, with combinations of antiangiogenic agents like ramucirumab and nintedanib with docetaxel offering new possibilities for patients who have already undergone first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New options for combination therapy for advanced non-squamous NSCLC. Rossi, A.[2020]

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. 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)

3. 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 ...

4. 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 ...

5. 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.