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 (OSTARA)

A Phase II, Open-label, Single-arm, Multi-centre Study to Evaluate 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 (OSTARA)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Osimertinib; Drug: Amivantamab

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Hong Kong, Hong Kong, 150001
    • Research Site
  • Hong Kong, Hong Kong, 999077
    • Research Site
  • Shatin, Hong Kong, 00000
    • Research Site
• Malaysia
  • George Town, Malaysia, 10990
    • Research Site
  • Kota Bharu, Malaysia, 15586
    • Research Site
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuala Lumpur, Malaysia, 50586
    • Research Site
  • Kuantan, Malaysia, 25100
    • Research Site
  • Kuching, Malaysia, 93200
    • Research Site
• Singapore
  • Singapore, Singapore, 169610
    • Research Site
  • Singapore, Singapore, 308433
    • Research Site
• South Korea
  • Anyang-si, South Korea, 14068
    • Research Site
  • Busan, South Korea, 49241
    • Research Site
  • Daegu, South Korea, 42415
    • Research Site
  • Seoul, South Korea, 08308
    • Research Site
  • Seoul, South Korea, 5030
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 82445
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 404
    • Research Site
  • Tainan, Taiwan, 73657
    • Research Site
  • Taipei, Taiwan, 10048
    • Research Site
  • Taipei, Taiwan, 110
    • Research Site
  • Yunlin, Taiwan, 640
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Songkhla, Thailand, 90110
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Osimertinib+Amivantamab; Participants will receive osimertinib and amivantamab.

Drug: 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from date of first dose of study intervention until the date of death due to any cause. The analysis will include all dosed participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy.	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)	The proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per RECIST 1.1. The analysis will include all dosed participants with measurable disease at baseline.	From screening (Day -28) to radiological disease progression (Approximately 52 months after the first participant is dosed)
Duration of Response (DoR)	The time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause. The analysis will include all dosed participants with measurable disease at baseline who have a confirmed response.	From screening (Day -28) to radiological disease progression (Approximately 52 months after the first participant is dosed)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Epidermal Growth Factor Receptor (EGFR); Non squamous; Epidermal Growth Factor Receptor mutation (EGFRm)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; amivantamab; osimertinib
• Other Study ID Numbers: D5162C00052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

• IPD Sharing 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
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No