Itacitinib + Osimertinib for Lung Cancer

Not currently recruiting at 35 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: itacitinib (a JAK inhibitor) and osimertinib (a targeted therapy drug), to assess their safety and tolerability for individuals with advanced or metastatic non-small cell lung cancer (NSCLC). The focus is on those with a specific mutation in their cancer related to the EGFR gene, who have experienced cancer progression after previous treatments. Suitable candidates have lung cancer that cannot be surgically removed and possess a known tumor mutation that qualifies them for this treatment. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Research has shown that osimertinib is a well-tolerated treatment for certain types of lung cancer, particularly effective for patients with specific genetic changes like the T790M mutation. Many patients prefer it, and it is already used to treat advanced non-small cell lung cancer (NSCLC) with these mutations.

Research on itacitinib is ongoing for its use in different conditions. It is currently being tested for safety when combined with osimertinib in lung cancer patients. The trial is in its early stages, and researchers are still collecting safety information. Testing itacitinib with an existing treatment like osimertinib suggests some initial confidence in its potential safety, but data from the trial will confirm this.

Overall, while osimertinib is known to be well-tolerated, itacitinib is still under study to determine its safety when used with osimertinib. Participants in the trial will provide valuable information about the safety of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Itacitinib + Osimertinib for lung cancer because these drugs bring a fresh approach to treatment. Unlike standard therapies such as platinum-based chemotherapy and older tyrosine kinase inhibitors, this combination targets specific pathways involved in cancer growth. Osimertinib targets the EGFR mutation, common in non-small cell lung cancer, while Itacitinib inhibits the JAK1 enzyme, potentially enhancing the effectiveness of Osimertinib. This dual approach not only aims to attack cancer cells more precisely but also hopes to reduce side effects compared to traditional chemotherapy.

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

Research has shown that osimertinib effectively treats non-small cell lung cancer (NSCLC) with certain mutations. This medicine targets specific changes in cancer cells, helping to slow or stop the disease. In this trial, participants will receive a combination of itacitinib and osimertinib. Researchers are still studying itacitinib, but they believe it works by blocking signals that help cancer cells grow. The goal of combining itacitinib with osimertinib is to enhance the overall treatment effect on the cancer. Early studies are examining how well these two medicines work together to combat advanced NSCLC. ^{4 5 6 7 8}

Who Is on the Research Team?

Peter Langmuir

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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

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

My lung cancer worsened after treatment with an EGFR inhibitor.

My cancer progressed after EGFR TKI treatment, and I have a T790M mutation.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02917993

An Open-Label Phase 1/2 Study of Itacitinib in ... The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally advanced or ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT02917993

UCSF Lung Cancer Trial → Itacitinib in Combination With ... The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally advanced or ...

3. clinicaltrial.be clinicaltrial.be/en/details/9771?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

An Open-Label Phase 1/2 Study of Itacitinib in Combinatio... The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally ...

4. withpower.com withpower.com/trial/phase-2-lung-neoplasms-11-2016-b52a7

Itacitinib + Osimertinib for Lung Cancer · Info for Participants Research shows that Osimertinib is effective for treating non-small-cell lung cancer (NSCLC) with specific mutations, offering good activity and less ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4940973/

The safety and efficacy of osimertinib for the ... - PubMed Central We review the rapid clinical development and approval of the third-generation EGFR TKI osimertinib for treatment of NSCLCs with EGFR-T790M.

6. dana-farber.org dana-farber.org/clinical-trials/17-218

An Open-Label Phase 1/2 Study of INCB039110 in ... The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally advanced or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6590181/

Efficacy and safety of osimertinib in treating EGFR‐mutated ... Osimertinib is a favorable treatment option for previously treated T790M mutation‐positive advanced NSCLC as well as a preferable therapy for untreated EGFR ...

8. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-first-patient-treated-phase-3-clinical-trial-1

Incyte Announces First Patient Treated in Phase 3 Clinical ... A Phase 3 study (GRAVITAS-301) of itacitinib for the treatment of patients with acute GVHD is already underway, with results expected in 2019.