EGF816 + Targeted Agents for Non-Small Cell Lung Cancer

Recruiting at 12 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

105 Participants Needed

Trial Summary

What is the purpose of this trial?

The study purpose is to evaluate the safety, tolerability, and preliminary efficacy of the addition of INC280, trametinib, ribociclib, gefitinib, or LXH254 to EGF816 in adult patients with advanced Epidermal growth factor receptor- mutant (EGFR-mutant) non-small cell lung cancer (NSCLC).

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.

What data supports the effectiveness of the drug combination EGF816 and other targeted agents for non-small cell lung cancer?

Research shows that gefitinib, one of the drugs in the combination, has been effective in treating advanced non-small cell lung cancer, with evidence of tumor shrinkage and good tolerability in patients. ^{1 2 3 4 5}

Is the treatment with EGF816 and related agents generally safe for humans?

Gefitinib (Iressa), one of the related agents, has been studied in patients with advanced non-small cell lung cancer and is generally well tolerated, with some patients experiencing tumor shrinkage. These studies suggest that the treatment is generally safe for humans, although individual experiences may vary. ^{1 2 3 5 6}

What makes the drug EGF816 + Targeted Agents unique for treating non-small cell lung cancer?

The combination of EGF816 with targeted agents like gefitinib (Iressa) is unique because it targets the epidermal growth factor receptor (EGFR), which is often involved in the growth of non-small cell lung cancer. Gefitinib is known for its ability to inhibit EGFR and has shown effectiveness in patients who have already been treated for advanced stages of this cancer, offering a novel approach by combining it with other targeted therapies. ^{1 2 3 5 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

References

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

Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer. [2023]

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

Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer. [2020]

4. Ireland pubmed.ncbi.nlm.nih.gov

Gefitinib as first-line, compassionate use therapy in patients with advanced non-small-cell lung cancer. [2018]

5. Ireland pubmed.ncbi.nlm.nih.gov

Outcomes of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839, "Iressa") on an expanded access study. [2018]

6. China pubmed.ncbi.nlm.nih.gov

[Treatment of non-small cell lung cancer with gefitinib]. [2018]

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

Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. [2022]