Osimertinib + Amivantamab for Lung Cancer

(OSTARA Trial)

Not currently recruiting at 29 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: CYP 3A4 inducers

Disqualifiers: Organ transplant, Active infection, ILD, 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

Compensation: Varies

Number of Visits: 7

Duration: Until disease progression or discontinuation

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two drugs, Osimertinib and Amivantamab, used together to treat non-small cell lung cancer (NSCLC) with specific genetic mutations. The trial targets individuals whose cancer has spread or cannot be treated with surgery or radiation. It seeks participants with non-squamous NSCLC and a specific mutation in the EGFR gene, which responds to these treatments. Those recently diagnosed with advanced NSCLC that cannot be surgically removed and have a confirmed EGFR mutation may find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use medications or supplements that are strong inducers of CYP 3A4, and any concurrent anti-cancer treatment requires an adequate washout period before starting the study.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take medications known to cause Torsade de Pointes or strong inducers of CYP 3A4. Also, any current anti-cancer treatment requires an adequate washout period (time without taking certain medications) before starting the trial.

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

Research has shown that both osimertinib and amivantamab have been studied for safety in people with lung cancer. Osimertinib is safe, with many patients tolerating it well. Studies indicate that side effects are manageable and may include mild skin and nail issues, diarrhea, and tiredness.

Amivantamab has also been tested with other treatments. It appears promising and is generally well-tolerated. However, some patients might experience side effects like a rash, reactions during infusions (such as fever or chills), and changes in blood cell counts.

These drugs are being studied together as a new treatment option. While side effects can occur, they are usually not severe. This combination aims to offer a chemotherapy-free option, potentially leading to fewer side effects overall. Safety data from past studies suggest that patients can expect a good balance of effectiveness and tolerability. Always consult a healthcare professional about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Osimertinib and Amivantamab for lung cancer because this duo targets cancer cells in a unique way. Osimertinib is already known for blocking a specific mutation in the EGFR gene, which is common in some lung cancers. Amivantamab adds a fresh twist by also targeting the EGFR pathway but with an additional focus on another mutation, MET, which can make cancers resistant to previous treatments. This combination aims to tackle both known and emerging mutations, potentially offering a more comprehensive attack on cancer cells compared to current single-target therapies.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

Research has shown that combining Osimertinib with Amivantamab, the focus of this trial, may effectively treat EGFR-mutated non-small cell lung cancer (NSCLC). Studies have found that this combination can extend the time patients live without their cancer worsening and reduce the likelihood of the cancer developing resistance, a common issue with Osimertinib alone. The combination is generally safe and rarely causes severe side effects. These findings suggest that Osimertinib with Amivantamab could be a promising initial treatment for individuals with advanced NSCLC that has an EGFR mutation. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or recurrent non-squamous Non-small Cell Lung Cancer (NSCLC) that can't be removed by surgery. Participants should have a life expectancy of more than 12 weeks, no prior advanced NSCLC treatment, and must not have certain health conditions like interstitial lung disease or heart problems.

Inclusion Criteria

I have a tumor that is at least 10 mm large and can be measured by CT or MRI.

Contraceptive use by males or females should be consistent with local regulations

My lung cancer is non-squamous based on lab tests.

Exclusion Criteria

I do not have an active infection, including TB, hepatitis B, or hepatitis C.

Should participants with HIV infection be included, patients are only eligible if they meet the criteria per protocol.

I have a heart condition as defined by the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive osimertinib and amivantamab from Day 1 until disease progression or study intervention discontinuation

Until disease progression or discontinuation

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at week 6, week 12, and every 12 weeks thereafter until radiological disease progression

Approximately 52 months

Visits at week 6, week 12, and every 12 weeks

Survival Follow-up

Survival follow-up will be performed every 12 weeks after study intervention discontinuation

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Osimertinib

Trial Overview

The study tests the combination of Osimertinib and Amivantamab as a first-line treatment for NSCLC patients with specific EGFR mutations. It aims to evaluate the safety and effectiveness of this drug duo in managing locally advanced or metastatic cancer.

How Is the Trial Designed?

Group I: Osimertinib+Amivantamab Experimental Treatment 2 Interventions

Participants will receive osimertinib and amivantamab.

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

Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., 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 study of 61 patients with advanced EGFR-mutant NSCLC, amivantamab showed a clinical response rate of 45.2% and a disease control rate of 64.3%, indicating its potential effectiveness beyond just exon 20 insertion mutations.

The combination of amivantamab with osimertinib and concurrent radiation therapy was found to be safe, with no additional toxicities reported, suggesting that this treatment approach could be a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). Wang, K., Du, R., Myall, NJ., et al.[2023]

Amivantamab, approved for treating non-small cell lung cancer with specific genetic mutations, works by targeting two pathways: the epithelial growth factor receptor and mesenchymal epithelial transition factor, enhancing the immune response against cancer cells.

Preclinical studies indicate that Amivantamab effectively inhibits cancer cell growth in models with exon20 insertions of the epithelial growth factor receptor, suggesting its potential as a targeted therapy for this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. Billowria, K., Das Gupta, G., Chawla, PA.[2023]

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET, specifically developed for treating non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations.

It received its first approval in the USA on May 21, 2021, for adult patients with advanced NSCLC who have progressed after platinum-based chemotherapy, and is currently in preregistration in multiple countries including the EU and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. Syed, YY.[2021]

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 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 a study of 62 patients with EGFR-mutated advanced non-small cell lung cancer, the combination of osimertinib and chemotherapy did not significantly improve progression-free survival compared to osimertinib alone, with median PFS of 15.8 months for monotherapy versus 14.6 months for the combination.

The overall response rate was higher in the osimertinib monotherapy group (71.4%) compared to the combination group (53.6%), and the safety profile of the combination treatment was comparable to previously reported data for carboplatin and pemetrexed, indicating it was generally tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib versus osimertinib plus chemotherapy for non-small cell lung cancer with EGFR (T790M)-associated resistance to initial EGFR inhibitor treatment: An open-label, randomised phase 2 clinical trial. Tanaka, K., Asahina, H., Kishimoto, J., et al.[2022]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

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