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

Inclusion Criteria:

• Histologically or cytologically documented non-squamous NSCLC. NSCLC of mixedhistology is allowed.

• Newly diagnosed locally advanced or metastatic NSCLC or recurrent non-squamousNSCLC, 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 commonEGFRm known to be associated with (Epidermal Growth Factor Receptor- Tyrosine KinaseInhibitor) EGFR-TKI sensitivity.

• At least 1 lesion that can be accurately measured at baseline as ≥10 mm in thelongest 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 theinvestigator's opinion makes it undesirable for the participant to participate inthe study or would jeopardise compliance with protocol.

• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability toswallow the osimertinib, or previous significant bowel resection that would precludeadequate absorption distribution, metabolism, or excretion of osimertinib.

• History of another primary malignancy except for malignancy treated with curativeintent with no known active disease ≥2 years.

• Any unresolved toxicities from prior therapy with Common Terminology Criteria forAdverse Events CTCAE) Grade ≥1, at the time of first dose of study intervention,with the exception of alopecia and Grade 2 prior platinum therapy relatedneuropathy.

• Spinal cord compression or brain metastases unless asymptomatic, stable, and notrequiring corticosteroids for at least 2 weeks prior to start of study intervention.

• Active infection, including tuberculosis and infections with HBV (verified by knownpositive HBsAg result) or HCV.

• Should participants with HIV infection be included, patients are only eligible ifthey meet the criteria per protocol.

• Patient with protocol defined cardiac issue.

• History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitisthat 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 amenableto 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 thefirst dose of study intervention.

• Palliative radiotherapy with a limited field of radiation within 2 weeks, or withwide field of radiation or to more than 30% of the bone marrow within 4 weeks, priorto 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 orinactive excipients of osimertinib, amivantamab, or recommended pre-treatments ofamivantamab or drugs with a similar chemical structure or class to these drugs.