Osimertinib + Amivantamab for Lung Cancer

(OSTARA Trial)

Recruiting at 23 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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two drugs, Osimertinib and Amivantamab, to treat a specific type of lung cancer. The study focuses on adults whose cancer has certain genetic changes and has either advanced locally or spread. Osimertinib works by stopping cancer cells from growing, while Amivantamab helps the immune system attack these cells. Osimertinib is a standard treatment for non-small cell lung cancer with EGFR mutations, and Amivantamab targets EGFR exon 20 insertion mutations, showing promise in early trials.

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.

What data supports the idea that Osimertinib + Amivantamab for Lung Cancer is an effective drug?

The available research shows that Amivantamab, when used with other treatments like lazertinib or chemotherapy, has shown positive results in treating non-small cell lung cancer (NSCLC), especially in cases where the cancer has progressed after other treatments. Although specific data on the combination of Osimertinib and Amivantamab is not directly mentioned, both drugs have individually shown effectiveness in treating NSCLC. Amivantamab has been approved for use in the USA for certain types of NSCLC, and Osimertinib is effective against a common mutation that causes resistance to other treatments. This suggests that the combination could be promising for patients with advanced NSCLC. ^{1 2 3 4 5}

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

Research shows that Amivantamab, when combined with other treatments like lazertinib, is effective in treating non-small cell lung cancer (NSCLC) that has progressed after using osimertinib. Additionally, Amivantamab has been approved for treating advanced NSCLC with specific genetic mutations, and Osimertinib is known to be effective in NSCLC with certain mutations. ^{1 2 3 4 5}

What safety data is available for the treatment of Osimertinib and Amivantamab in lung cancer?

Amivantamab (Rybrevant) has been approved for use in non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, with safety data indicating it is used after progression on platinum-based chemotherapy. Osimertinib (Tagrisso) is approved for NSCLC with certain mutations, with common adverse effects including leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough. The combination of Amivantamab and Lazertinib has shown efficacy in osimertinib-relapsed NSCLC, suggesting ongoing evaluation of safety in combination therapies. ^{2 3 4 6 7}

What safety information is available for the combination of Osimertinib and Amivantamab in treating lung cancer?

Osimertinib (Tagrisso) is known to cause side effects like low white blood cell counts, diarrhea, anemia, skin rash, muscle pain, and fatigue. Amivantamab (Rybrevant) has been approved for certain lung cancer patients, but specific safety data for the combination with Osimertinib is not detailed in the available research. ^{2 3 4 6 7}

Is the drug combination of Osimertinib and Amivantamab promising for lung cancer?

Yes, the combination of Osimertinib and Amivantamab is promising for lung cancer. Osimertinib is effective for certain lung cancers with specific mutations, and Amivantamab has shown positive results in treating lung cancer, especially when other treatments have failed. Together, they offer a strong potential for improving outcomes in lung cancer patients. ^{1 2 8 9 10}

What makes the drug combination of Osimertinib and Amivantamab unique for lung cancer?

The combination of Osimertinib and Amivantamab is unique because it targets specific mutations in non-small cell lung cancer (NSCLC), with Osimertinib being effective against the EGFR T790M mutation and Amivantamab being a bispecific antibody targeting EGFR and MET pathways, potentially overcoming resistance to previous treatments. ^{1 2 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

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

Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer. [2023]

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

Amivantamab: First Approval. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. [2023]

5. England 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. [2023]

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

New Adjuvant Drug for Lung Cancer. [2023]

7. Switzerland 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. [2023]

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

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). [2023]

9. 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]

10. England 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. [2022]