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 (TROPION-Lung14)

AstraZeneca

Status and phase

Enrolling

Phase 3

Conditions

Non-small Cell Lung Cancer

Treatments

Drug: Datopotamab Deruxtecan

Drug: Osimertinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT06350097

D516NC00001

2023-509883-89-00 (Other Identifier)

Details and patient eligibility

About

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:

The study duration will be event-driven, with an estimated duration of approximately 9 years.
Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.
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.

Full 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.

Enrollment

582 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 within 7 days before the first dose of study intervention.

Sex and Contraceptive/Barrier Requirements
Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Other Inclusion Criteria
All races, gender and ethnic groups are eligible for this study.

Exclusion criteria

As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, psychiatric illness/social situations), history of allogenic organ transplant, and/or substance abuse 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 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.
Known HIV infection that is not well controlled, as defined by Protocol.
Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
Resting ECG with clinically abnormal findings, as defined by Protocol.
Uncontrolled or significant cardiac disease, 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.

Prior/Concomitant Therapy
Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy.

Prior/Concurrent Clinical Study Experience
Participants with a known history of severe hypersensitivity reactions to either Dato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs with a similar chemical structure or class to DXd and osimertinib.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

582 participants in 2 patient groups

Arm 1: Osimertinib in combination with Datopotamab Deruxtecan

Experimental group

Description:

Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.

Treatment:

Drug: Osimertinib

Drug: Datopotamab Deruxtecan

Arm 2: Osimertinib monotherapy

Active Comparator group

Description:

Participants in this group will receive osimertinib 80 mg QD as oral tablet.

Treatment:

Drug: Osimertinib