Targeted Drug Therapy for Non-Small Cell Lung Cancer

Recruiting at 32 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SWOG Cancer Research Network

Must be taking: Osimertinib

Must not be taking: Anti-VEGF, MET inhibitors

Disqualifiers: Uncontrolled hypertension, Recent surgery, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

66 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II Lung-MAP treatment trial test the combination of targeted drugs (capmatinib, osimertinib, and/or ramucirumab) in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has EGFR and MET gene changes. Capmatinib and osimertinib are in a class of medications called kinase inhibitors. They work by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells and may help shrink tumors. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving capmatinib, osimertinib, and/or ramucirumab and targeting abnormal gene changes in tumor cells may be effective in shrinking or stabilizing advanced non-small cell lung cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain drugs like strong inducers of CYP3A4, CYP3A4 inhibitors, and others that affect specific enzymes or prolong the QT interval. Osimertinib can be continued up to the day before starting the trial treatment.

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

Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with a specific mutation (EGFR T790M) that often develops resistance to earlier treatments. In clinical trials, it achieved significant tumor response rates, with 57% and 61% of patients showing improvement in two separate studies. ^{1 2 3 4 5}

What makes the drug combination of Capmatinib and Osimertinib unique for treating non-small cell lung cancer?

This drug combination is unique because it targets specific genetic mutations in non-small cell lung cancer: Osimertinib targets the EGFR T790M mutation, which is common in patients who have developed resistance to previous treatments, while Capmatinib targets the MET exon 14 skipping mutation, providing a tailored approach for patients with these specific genetic profiles. ^{1 2 6 7 8}

Research Team

Sarah B Goldberg

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer that has spread and contains specific gene changes (EGFR and MET). Participants must have progressed on osimertinib treatment, be able to swallow pills, have adequate organ function, not be pregnant or breastfeeding, agree to use contraception if of reproductive potential, and not have certain medical conditions or treatments that could interfere with the study.

Inclusion Criteria

I have recovered from previous treatment side effects, except for hair loss or skin color loss.

Your hemoglobin level is lower than 9.0 grams per deciliter within the last 28 days before the study starts.

Your platelet count is at least 100,000 per microliter of blood within the last 28 days before the study starts.

Exclusion Criteria

I have not had a live vaccine in the last 28 days.

Participants must not be pregnant or breastfeeding (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of 'reproductive potential.' In addition to routine contraceptive methods, 'effective contraception' also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen

I haven't taken any cancer drugs (except osimertinib) in the last 21 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive capmatinib, osimertinib, and optionally ramucirumab, with regular CT or MRI scans and blood sample collections

Up to 3 years

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Capmatinib
• Osimertinib
• Ramucirumab

Trial Overview The trial tests a combination of targeted drugs: capmatinib (a kinase inhibitor), osimertinib (another kinase inhibitor), and ramucirumab (a monoclonal antibody). These drugs aim to block proteins signaling cancer cells to multiply and prevent tumor growth by stopping new blood vessels from forming. The effectiveness in shrinking or stabilizing lung cancer will be studied.

Participant Groups

Group I: Arm B (capmatinib, osimertinib) Experimental Treatment 5 Interventions

Patients receive capmatinib PO and osimertinib PO on study. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.

Group II: Arm A (capmatinib, osimertinib, ramucirumab) Experimental Treatment 6 Interventions

Patients receive capmatinib PO, osimertinib PO, and ramucirumab IV on study. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.

Capmatinib is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tabrecta for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping

Approved in European Union as Tabrecta for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping

Approved in Canada as Tabrecta for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

Capmatinib is an oral MET inhibitor specifically designed to target and inhibit cancer cell growth associated with the MET exon 14 skipping mutation, which is relevant for certain lung cancers.

In May 2020, capmatinib received FDA approval for treating adults with metastatic non-small cell lung cancer (NSCLC) that have this specific mutation, marking a significant advancement in targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capmatinib: First Approval. Dhillon, S.[2021]

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor specifically designed to target the EGFR T790M mutation, which is a common cause of resistance to first-line EGFR TKIs in advanced non-small-cell lung cancer.

This review highlights the efficacy of osimertinib in clinical trials, demonstrating its ability to effectively treat patients with non-small-cell lung cancer harboring the T790M mutation while minimizing effects on normal EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib making a breakthrough in lung cancer targeted therapy. Zhang, H.[2020]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

References

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

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

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

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Capmatinib: First Approval. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib making a breakthrough in lung cancer targeted therapy. [2020]

8. France pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]