Itacitinib + Osimertinib for Lung Cancer

Recruiting at 30 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Incyte Corporation

Must be taking: EGFR TKI

Must not be taking: JAK inhibitors, Osimertinib

Disqualifiers: CNS metastases, Cardiac disease, ILD, others

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

Compensation: Varies

Number of Visits: 8

Duration: Approximately 2 years

59 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of using two drugs, itacitinib and osimertinib, together. The study focuses on patients with advanced lung cancer that has spread. Itacitinib helps the immune system fight cancer, while osimertinib targets and kills specific cancer cells. Osimertinib is approved for treating a specific type of lung cancer, even in cases where the cancer has become resistant to other treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other anticancer treatments while participating.

What data supports the effectiveness of the drug combination Itacitinib and Osimertinib for lung cancer?

Research shows that Osimertinib is effective for treating non-small-cell lung cancer (NSCLC) with specific mutations, offering good activity and less toxicity compared to other treatments. It is particularly beneficial for patients with resistance to earlier treatments. ^{1 2 3 4 5}

What safety data exists for the treatment of Itacitinib and Osimertinib in humans?

Osimertinib has been studied in patients with lung cancer and is generally considered safe, but it can cause side effects like diarrhea, rash, dry skin, and fatigue. Rarely, it may lead to serious lung issues like interstitial pneumonitis (inflammation of lung tissue). ^{6 7 8 9 10}

How is the drug combination of Itacitinib and Osimertinib unique for lung cancer treatment?

The combination of Itacitinib and Osimertinib is unique because Osimertinib is a third-generation drug that targets specific mutations in lung cancer cells, offering less toxicity and better activity compared to older treatments. This combination may provide a novel approach by potentially enhancing the effectiveness of Osimertinib, although specific details about Itacitinib's role in this combination are not provided in the research. ^{1 2 8 11 12}

Research Team

Peter Langmuir

Principal Investigator

Incyte Corporation

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who have a specific EGFR mutation and have progressed after treatment with an EGFR tyrosine kinase inhibitor. They must not have untreated brain metastases, significant heart disease, or a history of certain lung conditions. Only one prior line of therapy for NSCLC is allowed in Phase 2.

Inclusion Criteria

I am at least 18 years old, or older if required by my country's laws.

My cancer has a specific EGFR mutation confirmed by a test.

My lung cancer worsened after treatment with an EGFR inhibitor.

Exclusion Criteria

I have been on a stable or decreasing dose of corticosteroids for at least 4 weeks.

I haven't had any cancer except for certain skin, bladder, prostate, cervical, or other noninvasive cancers in the last 2 years.

I am not currently undergoing any cancer treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive itacitinib in combination with osimertinib to evaluate safety and tolerability

Approximately 2 years

8-week intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Itacitinib
• Osimertinib

Trial Overview The study tests the safety and effectiveness of combining Itacitinib with Osimertinib in treating NSCLC. Participants will receive both drugs to see how well they work together against lung cancer that has worsened despite previous treatments.

Participant Groups

Group I: Itacitinib + osimertinib Experimental Treatment 2 Interventions

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

Approved in European Union as Itacitinib for:

• Graft-versus-host disease

Approved in United States as Itacitinib for:

• Graft-versus-host disease

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., 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]

Hsp90 inhibitors, such as ganetespib and luminespib, effectively reduce cell viability and colony formation in osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines, suggesting they can enhance the effectiveness of osimertinib.

The combination of luminespib with osimertinib significantly decreases the expression of key proteins associated with resistance, indicating a potential strategy to overcome resistance in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hsp90 inhibitors enhance the antitumoral effect of osimertinib in parental and osimertinib-resistant non-small cell lung cancer cell lines. Codony-Servat, J., Viteri, S., Codony-Servat, C., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

A 60-year-old male patient with advanced non-small cell lung cancer (NSCLC) developed early-onset interstitial pneumonitis just two days after starting a combination treatment of crizotinib and osimertinib, highlighting a significant safety concern.

This case underscores the risk of interstitial pneumonitis associated with both crizotinib and osimertinib, particularly in patients with elevated MET copy number amplification who may be resistant to osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-onset interstitial pneumonitis in a patient with advanced non-small cell lung cancer treated with crizotinib and osimertinib. Cheng, Y., Yu, Q., Xiong, Y., et al.[2022]

In a study involving six patients with EGFR-mutated lung adenocarcinoma, the combination of osimertinib and ramucirumab was found to be generally safe, with only one case of dose-limiting toxicity (grade 3 appetite loss) and no other severe adverse events reported.

Five out of six patients showed a partial response to the treatment, with a median progression-free survival of 9.2 months for those with the EGFR T790M mutation, suggesting promising efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. Akamatsu, H., Ozawa, Y., Oyanagi, J., et al.[2023]

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]

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]

In vitro studies identified the BRAF G469A mutation as a key mechanism of acquired resistance to osimertinib in non-small cell lung cancer cells, indicating that this mutation allows cancer cells to continue growing despite treatment.

Treatment with selumetinib and trametinib was effective in restoring sensitivity to osimertinib and increasing cell death in resistant clones, suggesting potential strategies to overcome resistance in patients with this mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion. La Monica, S., Minari, R., Cretella, D., et al.[2022]

References

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

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of osimertinib for patients with EGFR-mutated NSCLC: a systematic review and meta-analysis of randomized controlled studies. [2022]

3. Singapore pubmed.ncbi.nlm.nih.gov

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor: A retrospective multicenter study of its real-world efficacy and safety in advanced/recurrent non-small cell lung carcinoma. [2022]

4. 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]

5. China pubmed.ncbi.nlm.nih.gov

Hsp90 inhibitors enhance the antitumoral effect of osimertinib in parental and osimertinib-resistant non-small cell lung cancer cell lines. [2022]

6. England pubmed.ncbi.nlm.nih.gov

ASTRIS: a global real-world study of osimertinib in >3000 patients with EGFR T790M positive non-small-cell lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Early-onset interstitial pneumonitis in a patient with advanced non-small cell lung cancer treated with crizotinib and osimertinib. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]

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

New Adjuvant Drug for Lung Cancer. [2023]

11. 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]

12. France pubmed.ncbi.nlm.nih.gov

Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion. [2022]