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

NCT05801029 | Active Not Recruiting Phase 2

• 1 other identifier: D5162C00052
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 29

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).

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Keywords

NSCLC; Non squamous; Epidermal Growth Factor Receptor (EGFR); Epidermal Growth Factor Receptor mutation (EGFRm)

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events (AEs)

  To assess the safety and tolerability of osimertinib plus amivantamab in participants with EGFR mutation-positive, locally advanced, or metastatic NSCLC.

  From screening (Day-28) to survival follow up (Approximately 52 months after the first participant is dosed)

• Progression Free Survival (PFS)

  The time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause. The analysis will include all dosed participants. All events will be included, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1.

  From date of first dose of study intervention until radiological disease progression or death due to any cause (Approximately 52 months after the first participant is dosed)

Secondary Outcomes (3)

• Overall Survival (OS)

  From date of first dose of study intervention until death due to any cause. Landmarks at 18 and 24 months. (Approximately 52 months after the first participant is dosed)

• Objective Response Rate (ORR)

  From screening (Day -28) to radiological disease progression (Approximately 52 months after the first participant is dosed)

• Duration of Response (DoR)

  From screening (Day -28) to radiological disease progression (Approximately 52 months after the first participant is dosed)

Study Arms (1)

Osimertinib+Amivantamab

EXPERIMENTAL

Participants will receive osimertinib and amivantamab.

Drug: Osimertinib; Drug: Amivantamab

Interventions

Osimertinib 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.

Osimertinib+Amivantamab

Amivantamab 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.

Osimertinib+Amivantamab

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Parexel: collaborator
• AstraZeneca: lead

Study Sites (29)

Research Site

Hong Kong, 150001, Hong Kong

Location

Research Site

Hong Kong, 999077, Hong Kong

Location

Research Site

Hong Kong, Hong Kong

Location

Research Site

Shatin, 00000, Hong Kong

Location

Research Site

George Town, 10990, Malaysia

Location

Research Site

Kota Bharu, 15586, Malaysia

Location

Research Site

Kuala Lumpur, 50586, Malaysia

Location

Research Site

Kuala Lumpur, 59100, Malaysia

Location

Research Site

Kuantan, 25100, Malaysia

Location

Research Site

Kuching, 93200, Malaysia

Location

Research Site

Singapore, 169610, Singapore

Location

Research Site

Singapore, 308433, Singapore

Location

Research Site

Anyang-si, 14068, South Korea

Location

Research Site

Busan, 49241, South Korea

Location

Research Site

Daegu, 42415, South Korea

Location

Research Site

Seoul, 08308, South Korea

Location

Research Site

Seoul, 5030, South Korea

Location

Research Site

Kaohsiung City, 82445, Taiwan

Location

Research Site

Taichung, 404, Taiwan

Location

Research Site

Taichung, 40705, Taiwan

Location

Research Site

Tainan, 73657, Taiwan

Location

Research Site

Taipei, 10048, Taiwan

Location

Research Site

Taipei, 110, Taiwan

Location

Research Site

Yunlin, 640, Taiwan

Location

Research Site

Bangkok, 10330, Thailand

Location

Research Site

Bangkok, 10400, Thailand

Location

Research Site

Bangkok, 10700, Thailand

Location

Research Site

Chiang Mai, 50200, Thailand

Location

Research Site

Songkhla, 90110, Thailand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; amivantamab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 6, 2023
• Study Start: July 18, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

TH (5); SG (2); HK (4); TW (7); MY (6); KR (5)