EGF816 + Targeted Agents for Non-Small Cell Lung Cancer

Not currently recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must be taking: EGFR TKI

Must not be taking: 3rd generation EGFR TKI

Disqualifiers: Interstitial lung disease, Unstable brain metastases, HIV, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new combinations of treatments for individuals with advanced non-small cell lung cancer (NSCLC) that has a specific EGFR gene mutation. Researchers aim to determine if combining EGF816 (an experimental treatment) with other drugs like INC280, trametinib, ribociclib, gefitinib, or LXH254 is safe and more effective against the cancer. Suitable candidates have NSCLC with an EGFR mutation and have not received certain prior treatments. The goal is to discover a more effective treatment for this type of lung cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific time frames for stopping certain cancer treatments before joining the trial, such as 2 weeks for some therapies and 4 to 6 weeks for others.

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

Research shows that the treatments tested in this trial are generally safe, though some side effects can occur. For the EGF816 and ribociclib combination, earlier studies found that EGF816, also known as nazartinib, often causes mild skin rashes, which can be managed. Ribociclib, approved for breast cancer, is usually well-tolerated but may cause common side effects like tiredness and nausea.

For the EGF816 and INC280 (capmatinib) combination, research suggests it is safe even for patients who have not responded to other treatments. Some mild to moderate side effects, such as upset stomach and tiredness, have been observed.

The EGF816 and LXH254 combination remains under study, so detailed safety information is limited. However, EGF816 itself generally causes only mild side effects.

For EGF816 and trametinib, early data indicate they are usually well-tolerated. Trametinib is FDA-approved for other cancers and may cause mild side effects like skin issues and tiredness.

Lastly, for the EGF816 and gefitinib combination, both drugs target specific cancer mutations and are generally considered safe. Gefitinib has been widely used and can cause mild side effects like diarrhea or skin reactions.

Overall, while these combinations are still being researched, past studies suggest they are relatively safe with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they explore new combinations of targeted therapies that could overcome resistance to existing treatments. Unlike standard options like chemotherapy and existing targeted drugs, these investigational treatments use EGF816, which specifically targets mutations in cancer cells to stop their growth. For example, combining EGF816 with INC280 or ribociclib could address resistance mechanisms that make current treatments less effective. By targeting specific pathways involved in cancer cell survival, these combinations could offer more personalized and potentially more effective options for patients with known or unknown resistance to other therapies.

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

This trial will explore various combinations of EGF816 with targeted agents for non-small cell lung cancer. Research has shown that combining EGF816 and ribociclib, which some trial arms may include, can effectively treat certain cancers. Ribociclib alone has improved survival rates in breast cancer patients. In other trial arms, EGF816 will be combined with INC280, a MET inhibitor, which demonstrated a 74.4% response rate and over five months without cancer progression in lung cancer patients. The combination of EGF816 and trametinib, another option in this trial, has shown promise in stopping tumor growth by targeting specific cancer pathways. Additionally, EGF816 and gefitinib, studied in separate trial arms, have effectively targeted mutations in lung cancer, helping patients live longer without disease progression. Each combination targets specific pathways to potentially halt cancer progression. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis

Are You a Good Fit for This Trial?

This trial is for adults with advanced EGFR-mutant NSCLC who haven't had treatment yet or have specific mutations after initial therapy. They must have a tumor that can be biopsied and agree to the procedure. Excluded are those in other drug studies, with unstable brain tumors, lung conditions like pneumonitis, HIV, recent certain therapies, uncontrolled heart disease, or another cancer history.

Inclusion Criteria

My cancer has specific genetic changes known as EGFR and T790M mutations.

My lung cancer is advanced or has spread, and tests show it has specific EGFR mutations.

I am willing to have a biopsy of my cancer.

Exclusion Criteria

Patients participating in additional parallel investigational drug or medical device studies.

I have or had lung conditions like interstitial lung disease.

I have had another type of cancer in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients are assigned to the addition of trametinib, ribociclib, or LXH254 to EGF816 to determine the recommended dose

4 weeks

1 visit per week (in-person)

Dose Expansion

Patients are enrolled to the dose expansion arms of EGF816 in combination with ribociclib, trametinib, LXH254, or INC280

Approximately 4 years

Every 8-12 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EGF816
• Gefitinib
• INC280
• LXH254
• Ribociclib
• Trametinib

Trial Overview The study tests how safe and effective EGF816 is when combined with INC280, trametinib, ribociclib, gefitinib, or LXH254 in patients with advanced EGFR-mutant NSCLC. It aims to find out if adding these targeted agents improves outcomes for these patients.

How Is the Trial Designed?

Group I: Arm G Experimental Treatment 2 Interventions

EGF816 + INC280 in expansion phase (patients with known resistance mechanism)

Group II: Arm F Experimental Treatment 2 Interventions

EGF816 + gefitinib in expansion phase

Group III: Arm E Experimental Treatment 2 Interventions

EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)

Group IV: Arm D Experimental Treatment 2 Interventions

EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)

Group V: Arm C Experimental Treatment 2 Interventions

EGF816 + ribociclib in expansion phase

Group VI: Arm B Experimental Treatment 2 Interventions

EGF816 + trametinib in expansion phase

Group VII: Arm A Experimental Treatment 2 Interventions

EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)

Group VIII: Arm 3 Experimental Treatment 2 Interventions

EGF816 + LXH254 in escalation phase

Group IX: Arm 2 Experimental Treatment 2 Interventions

EGF816 + ribociclib in escalation phase

Group X: Arm 1 Experimental Treatment 2 Interventions

EGF816+ trametinib in escalation phase

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03292133

A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant ... Both EGF816 and gefitinib are inhibitors which target a specific mutation in cancer and may stop tumors growing and multiplying. Official Title. A Phase 2 Study ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3110340/

Gefitinib in Non Small Cell Lung Cancer - PMC The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0909530

Gefitinib or Chemotherapy for Non–Small-Cell Lung ... First-line gefitinib for patients with advanced non–small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1698934/

Gefitinib (IRESSA) sensitive lung cancer cell lines show ... These data indicate that improved patient selection and combination strategies are probably required to maximize the benefits of using this targeted therapy.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0954611104003087

a new therapy for advanced non-small-cell lung cancer It is unclear why the combination of gefitinib with standard doublet chemotherapy failed to show survival benefits in the first-line setting. Possible ...

6. apm.amegroups.org apm.amegroups.org/article/view/60116/html

Efficacy and safety of domestic and imported gefitinib in ... This study included 227 patients with advanced non-small cell lung cancer (NSCLC) who received gefitinib treatment in four medical institutions.