A Study to Investigate Safety and Efficacy of Osimertinib and Amivantamab in Participants With Non-small Cell Lung Cancer With Common Epidermal Growth Factor Receptor Mutations

NCT ID: NCT05801029

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-18
• Study Completion Date: 2027-10-01

Brief Summary

This study will assess the safety and efficacy of Osimertinib with Amivantamab as First-line Treatment in Participants with Epidermal Growth Factor Receptor Mutation-Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC).

Detailed Description

This is a Phase II, open-label, single-arm, multi-centre study to assess the safety and efficacy of osimertinib with amivantamab as first-line treatment in adult participants with a local preexisting positive approved tissue test result for EGFRm (Ex19del or L858R), locally advanced (clinical stage IIIB, IIIC), metastatic (clinical stage IVA or IVB), or recurrent non-squamous NSCLC.

This study consists of screening period of 28 days, followed by the study intervention period wherein the participant receives treatment from Day 1 until disease progression or study intervention discontinuation. Participants will be followed up at week 6 (± 1 week), week 12 (± 1 week), then every 12 weeks (± 1 week) until radiological disease progression. Survival follow up will be performed every 12 weeks. Upon study intervention discontinuation a 28 day follow up visit will be performed.

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Osimertinib+Amivantamab

Participants will receive osimertinib and amivantamab.

Group Type: EXPERIMENTAL

Osimertinib

Intervention Type: DRUG

Osimertinib will be administered as 80 mg oral tablet once daily (from Day 2) until progression of disease or until a study intervention discontinuation criterion is met.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an IV infusion at 1050 mg (\< 80 kg body weight) or 1400mg (≥ 80 kg body weight) (in 28-day cycles: once weekly in Cycle 1 (with a split dose on Days 1 to 2) and then every 2 weeks in subsequent cycles) until progression of disease or until a study intervention discontinuation criterion is met. The first cycle dose is spilt over 2 days- 350 mg on day 1 and 700 mg \[body weight \< 80 kg\] or 1050 mg \[body weight ≥ 80 kg\] on day 2.

Interventions

Osimertinib

Osimertinib will be administered as 80 mg oral tablet once daily (from Day 2) until progression of disease or until a study intervention discontinuation criterion is met.

Intervention Type: DRUG

Amivantamab

Amivantamab will be administered as an IV infusion at 1050 mg (\< 80 kg body weight) or 1400mg (≥ 80 kg body weight) (in 28-day cycles: once weekly in Cycle 1 (with a split dose on Days 1 to 2) and then every 2 weeks in subsequent cycles) until progression of disease or until a study intervention discontinuation criterion is met. The first cycle dose is spilt over 2 days- 350 mg on day 1 and 700 mg \[body weight \< 80 kg\] or 1050 mg \[body weight ≥ 80 kg\] on day 2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically documented non-squamous NSCLC. NSCLC of mixed histology is allowed.
• Newly diagnosed locally advanced or metastatic NSCLC or recurrent non-squamous NSCLC, not amenable to curative surgery or radiotherapy.
• WHO PS of 0 to 1 with no deterioration over the 2 weeks prior to enrolment.
• Minimum life expectancy > 12 weeks at Day 1.
• Confirmation by the local laboratory that the tumour harbours one of the 2 common EGFRm known to be associated with (Epidermal Growth Factor Receptor- Tyrosine Kinase Inhibitor) EGFR-TKI sensitivity.
• At least 1 lesion that can be accurately measured at baseline as ≥10 mm in the longest diameter with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements.
• Contraceptive use by males or females should be consistent with local regulations

Exclusion Criteria

• Any evidence of diseases, history of allogenic organ transplant, which in the investigator's opinion makes it undesirable for the participant to participate in the study or would jeopardise compliance with protocol.
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the osimertinib, or previous significant bowel resection that would preclude adequate absorption distribution, metabolism, or excretion of osimertinib.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥2 years.
• Any unresolved toxicities from prior therapy with Common Terminology Criteria for Adverse Events CTCAE) Grade ≥1, at the time of first dose of study intervention, with the exception of alopecia and Grade 2 prior platinum therapy related neuropathy.
• Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring corticosteroids for at least 2 weeks prior to start of study intervention.
• Active infection, including tuberculosis and infections with HBV (verified by known positive HBsAg result) or HCV.
• Should participants with HIV infection be included, patients are only eligible if they meet the criteria per protocol.
• Patient with protocol defined cardiac issue.
• History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
• Any concomitant medications known to be associated with Torsade de Pointes.
• Prior exposure to any systemic anti-cancer therapy for advanced NSCLC not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug.
• Any concurrent anti-cancer treatment without an adequate washout period prior to the first dose of study intervention.
• Palliative radiotherapy with a limited field of radiation within 2 weeks, or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
• Major surgical procedure or significant traumatic injury.
• Current use of medications or herbal supplements known to be strong inducers of CYP 3A4.
• Prior treatment with an EGFR-TKI.
• Participants with a history of hypersensitivity, or intolerance to the active or inactive excipients of osimertinib, amivantamab, or recommended pre-treatments of amivantamab or drugs with a similar chemical structure or class to these drugs.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Hong Kong, , Hong Kong

Research Site

Hong Kong, , Hong Kong

Research Site

Hong Kong, , Hong Kong

Research Site

Shatin, , Hong Kong

Research Site

George Town, , Malaysia

Research Site

Kota Bharu, , Malaysia

Research Site

Kuala Lumpur, , Malaysia

Research Site

Kuala Lumpur, , Malaysia

Research Site

Kuantan, , Malaysia

Research Site

Kuching, , Malaysia

Research Site

Singapore, , Singapore

Research Site

Singapore, , Singapore

Research Site

Anyang-si, , South Korea

Research Site

Busan, , South Korea

Research Site

Daegu, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Kaohsiung City, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Tainan, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Yunlin, , Taiwan

Research Site

Bangkok, , Thailand

Research Site

Bangkok, , Thailand

Research Site

Bangkok, , Thailand

Research Site

Chiang Mai, , Thailand

Research Site

Songkhla, , Thailand

Countries

Hong Kong; Malaysia; Singapore; South Korea; Taiwan; Thailand

Other Identifiers

D5162C00052

Identifier Type: -

Identifier Source: org_study_id