JDQ443 for Non-Small Cell Lung Cancer

(KontRASt-06 Trial)

Recruiting at 77 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Strong CYP3A inducers

Disqualifiers: EGFR mutation, ALK rearrangement, CNS metastases, 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

Duration: 21 days per cycle, up to approximately 24 months

96 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression \< 1% (cohort A) or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A inducers (a type of medication that affects how drugs are processed in the body) at least seven days before starting the study treatment and for the duration of the study. If you are on such medications, you will need to discontinue them.

What data supports the effectiveness of the drug JDQ443 for non-small cell lung cancer?

While there is no direct data on JDQ443, similar drugs like nivolumab, which also target immune checkpoints, have shown effectiveness in treating non-small cell lung cancer by enhancing the immune system's ability to fight cancer. Nivolumab has demonstrated a 1-year overall survival rate of 45% and a progression-free survival rate at 24 weeks of 42% in patients with this type of cancer. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has a specific mutation (KRAS G12C). Participants must have a PD-L1 expression level below 1% or above 1% with an STK11 co-mutation, and should not have had previous systemic treatment for metastatic NSCLC. They need to be able to swallow pills, have at least one measurable tumor lesion, and be in good physical condition.

Inclusion Criteria

I had chemotherapy, immunotherapy, or radiotherapy over a year ago for early-stage cancer.

My cancer has PD-L1 expression of 1% or more and an STK11 mutation.

My cancer has PD-L1 expression under 1%, STK11 mutation status doesn't matter.

Exclusion Criteria

My cancer has EGFR mutation or ALK rearrangement.

I have a condition that makes my skin extra sensitive to sunlight.

I am not taking any strong medications that can't be stopped a week before starting the study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JDQ443 single-agent as first-line treatment for locally advanced or metastatic KRAS G12C-mutated NSCLC

21 days per cycle, up to approximately 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Treatment Details

Interventions

• JDQ443

Trial Overview The study tests JDQ443 as the first-line treatment for NSCLC patients with KRAS G12C mutations. It's divided into two groups based on their PD-L1 expression levels: one group has less than 1%, while the other has more than 1% plus an STK11 mutation. The drug's effectiveness and safety are being evaluated.

Participant Groups

Group I: Cohort B- PD-L1≥ 1% and STK11 mutation Experimental Treatment 1 Intervention

Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.

Group II: Cohort A- PD-L1<1% Experimental Treatment 1 Intervention

Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.

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

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, 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]

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]

References

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

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical features affecting survival in metastatic NSCLC treated with immunotherapy: A critical review of published data. [2020]

3. United States 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. [2019]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? [2022]