Dacomitinib + Osimertinib for Lung Cancer

Not currently recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Recent surgery, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of combining two drugs, dacomitinib and osimertinib, for individuals with a specific type of lung cancer. It focuses on those with metastatic non-small cell lung cancer that has a certain gene mutation (EGFR) and has not been treated with an EGFR inhibitor. Participants must have this gene mutation confirmed through a tumor biopsy and should not have previously used EGFR inhibitors. The study aims to determine the correct dosage and observe any effects these drugs may have. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have not been treated with any EGFR inhibitors before. If you are on other medications, it's best to discuss with the trial team to see if they are compatible with the study drugs.

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

Research shows that using dacomitinib and osimertinib together is generally safe, with manageable side effects. Studies have found that patients taking these drugs might experience common side effects such as diarrhea, skin rash, and tiredness, which are typical for treatments targeting a specific type of lung cancer.

In earlier research, patients tolerated the combination well, but regular check-ups remain important to adjust doses if needed. The drugs are being tested to find the right balance between efficacy and side effects. While further studies are underway to confirm safety, early results appear promising for individuals with certain types of lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of dacomitinib and osimertinib for lung cancer because it targets cancer cells in a unique way compared to standard treatments like chemotherapy and radiation. Dacomitinib and osimertinib are both tyrosine kinase inhibitors, but they work on different pathways, potentially offering a more comprehensive attack on cancer cells. By combining these two drugs, there's a possibility of overcoming resistance to previous treatments and improving outcomes for patients with specific types of lung cancer. This dual approach could pave the way for more effective and personalized treatment options.

What evidence suggests that the combination of dacomitinib and osimertinib could be effective for metastatic EGFR mutant lung cancer?

Studies have shown that the drugs dacomitinib and osimertinib effectively treat certain types of lung cancer with specific genetic changes. Dacomitinib has helped patients live longer compared to drugs like gefitinib for similar conditions. Research suggests that dacomitinib might also be beneficial when osimertinib stops working, which can occur during treatment. In this trial, participants will receive a combination of dacomitinib and osimertinib. Early findings indicate that using these two drugs together could lead to better outcomes for patients who haven't yet received a specific type of targeted cancer therapy. These results offer hope for people with certain lung cancer mutations that other treatments might not address as well. ^{1 2 3 6 7}

Who Is on the Research Team?

Helena Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer that has a specific EGFR mutation. They must not have had prior EGFR inhibitor treatments but can have other chemotherapies. Participants need to be in good physical condition, able to take oral meds, and willing to use birth control. People with recent surgeries or radiotherapy, significant heart issues, interstitial lung disease, uncontrolled side effects from past treatments, or certain ECG abnormalities cannot join.

Inclusion Criteria

Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential)

Written informed consent

I can swallow pills.

Exclusion Criteria

I do not have any active lung diseases that affect the tissue and space around the air sacs.

Pregnant or lactating women

I have not had any radiation therapy in the week before starting the treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination dacomitinib and osimertinib with dose escalation over 28-day cycles

1 year

Telemedicine visits may be utilized for cycles without imaging; physical exams, vital signs, and labs concurrent with imaging visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dacomitinib
• Osimertinib

Trial Overview The study tests the safety of combining two drugs—Dacomitinib and Osimertinib—at increasing doses on patients with metastatic EGFR mutant lung cancer who haven't been treated with an EGFR TKI before. The goal is to find out the effects of this drug combination.

How Is the Trial Designed?

Group I: Dacomitinib and Osimertinib Experimental Treatment 2 Interventions

Patients will begin on combination dacomitinib and osimertinib at the prescribed doses. A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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]

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]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

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 phase 2 study involving 210 patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), osimertinib demonstrated significant efficacy, with 70% of patients achieving an objective response, including 3% with complete responses.

Osimertinib was found to have manageable side effects, although serious adverse events occurred in 25% of patients, with interstitial lung disease being the only fatal event possibly related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Goss, G., Tsai, CM., Shepherd, FA., et al.[2022]

Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, was effective for 2.5 years in a 78-year-old woman with T790M-positive lung cancer, but she eventually experienced disease progression due to the emergence of a new resistance mutation (C797G).

The case highlights the potential of liquid biopsy and next-generation sequencing to monitor clonal evolution and identify novel resistance mechanisms in patients treated with osimertinib, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. DE Carlo, E., Schiappacassi, M., Pelizzari, G., et al.[2022]

Osimertinib (AZD9291) is effective in prolonging survival for non-small cell lung cancer patients with EGFR mutations, but resistance to the drug is a common issue, prompting the need to explore resistance mechanisms.

In this study, AZD9291-resistant NSCLC cell lines were established, revealing significant changes in circular RNA (circRNA) expression profiles, which may contribute to drug resistance and could serve as potential targets for future gene therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. Chen, T., Luo, J., Gu, Y., et al.[2022]

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 a third-generation EGFR tyrosine kinase inhibitor that effectively targets specific mutations in advanced non-small cell lung cancer (NSCLC), including the T790M mutation, leading to significantly longer progression-free survival compared to first-generation EGFR TKIs like erlotinib or gefitinib.

The benefits of osimertinib in prolonging progression-free survival were consistent across all patient groups, regardless of the type of EGFR mutation or the presence of CNS metastases, and it has a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Scott, LJ.[2020]

In a study of 46 treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer, alternating therapy with osimertinib and afatinib resulted in a median progression-free survival of 21.3 months, indicating promising efficacy despite not meeting the primary endpoint of 12-month progression-free survival probability.

The treatment was generally well-tolerated, with common side effects including diarrhea (73.9%) and rash (63.0%), and only a few cases of serious pneumonitis, suggesting a manageable safety profile for this alternating therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L). Hayashi, H., Yonesaka, K., Nakamura, A., et al.[2022]

Citations

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Real-world data of dacomitinib as first-line treatment for ... Dacomitinib demonstrated superior survival benefit compared to gefitinib as a first-line treatment in non-small cell lung cancer (NSCLC) ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/29/8/1423/725071/Brief-Report-Combination-of-Osimertinib-and

Brief Report: Combination of Osimertinib and Dacomitinib to ... In the acquired resistance trial, dacomitinib with or without osimertinib was administered to patients with EGFR-mutant lung cancers with disease progression on ...

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Identification of optimal dosing schedules of dacomitinib ... Here we present an integrated computational modeling and experimental approach to identify an optimal dosing schedule for osimertinib and dacomitinib ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11245257/

Dacomitinib overcomes acquired resistance to osimertinib ... Dacomitinib is a potential treatment option for NSCLC patients with EGFR L718Q mutation after resistance to Osimertinib.

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Study of Dacomitinib and Osimertinib for Patients With ... The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing doses, to find out what effects, if any, this combination of ...

7. michorlab.dfci.harvard.edu michorlab.dfci.harvard.edu/pfiles/Combination-of-osimertinib-and-dacomitinib-to-mitigate-primary-and-acquired-resistance-in-EGFR-mutant-non-small-cell-lung-cancer.pdf

Brief Report: Combination of Osimertinib and Dacomitinib to ... Afatinib and dacomitinib efficacy, safety, progression patterns, and resistance mechanisms in patients with non-small cell lung cancer carrying uncommon EGFR.