Recruiting NCT06350097

Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

Phase III Interventional Non-small Cell Lung Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Osimertinib, Datopotamab Deruxtecan.
Who it may be relevant to: Registry conditions: Non-small Cell Lung Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Brazil, Canada, China +14
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Phase III, Open-label, Randomised Study of Osimertinib With or Without Datopotamab Deruxtecan (Dato-DXd), as First-line Treatment in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer

Overview

The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Dato-DXd (i.v. infusion) compared with osimertinib (tablet) monotherapyas a first-line therapy in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC. Study details include: 1. The study duration will be event-driven, with an estimated duration of approximately 8 years. 2. Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met. 3. The visit frequency will be every 3 weeks during the treatment period. Note: Participants on osimertinib treatment(osimertinib only arm or who have discontinued Dato-DXd while are still receiving osimertinib) are required to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and then visits every 12 weeks until disease progression or IP discontinuation. Participants who are receiving osimertinib + Dato-DXd are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA.

Detailed description

This is a global Phase III, open-label, randomised, multicentre study assessing the efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC who have not received any prior therapy for advanced disease.

Interventions

Drug Osimertinib
Osimertinib 80 mg administered orally once daily (QD).
Drug Datopotamab Deruxtecan
Datopotamab Deruxtecan 6 mg/kg administered as an intravenous (i.v.) infusion every 3 weeks (q3w).

Primary outcome measures

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants. [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]

Secondary outcome measures (11)

To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Survival (OS) in all randomised participants. [Time frame: It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on Central nervous system (CNS) metastases in participants with CNS metastases at baseline [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants. [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Response Rate (ORR) in all randomised participants with measurable disease at baseline. [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Duration of Response (DoR) in all randomised participants with measurable disease at baseline. [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants [Time frame: It is anticipated that it will be analyzed by time of PFS primary which is about 3 years after the first participant has been randomised.]
To assess the Pharmacokinetics (PK) of osimertinib and Datopotamab Deruxtecan [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised.]
To investigate the immunogenicity of Datopotamab Deruxtecan [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.]
To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.]
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations [Time frame: It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.]

Eligibility criteria

Inclusion criteria

Age

Participant must be ≥ 18 years.

Type of Participant and Disease Characteristics

Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
The tumour harbors at least 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
WHO performance status of 0 or 1.
At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements.
Adequate bone marrow reserve and organ function before the first dose of study intervention.

Exclusion criteria

As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
History of another primary malignancy.
Spinal cord compression and/or unstable brain metastases, as defined by Protocol.
Clinically significant corneal disease.
Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise.
Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment

Study locations

United States · 36 centers

Research Site — Fountain Valley
Research Site — Los Alamitos
Research Site — Los Angeles
Research Site — Los Angeles
Research Site — Orange
Research Site — San Diego
Research Site — Santa Monica
Research Site — Walnut Creek
… and 28 more centers

China · 33 centers

Research Site — Beijing
Research Site — Beijing
Research Site — Beijing
Research Site — Changchun
Research Site — Changsha
Research Site — Chengdu
Research Site — Chengdu
Research Site — Chengdu
… and 25 more centers

India · 11 centers