A study to investigate safety and efficacy with Dato-DXd as IV infusion in participants aged 18 years of age or older with previously treated nonsquamous advanced or metastatic NSCLC - TROPION-Lung13

Exclusion Criteria

• 1. Symptomatic or clinically active central nervous system metastases that require immediate local treatment. Leptomeningeal carcinomatosis or metastasis.
• 2. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases and significant cardiac or psychological conditions), 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.
• 3. History of (non-infectious) ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• 4. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of study Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren’s syndrome, sarcoidosis, etc.), or prior pneumonectomy.
• 5. History of another primary malignancy except for solid malignancy treated with curative intent with no known active disease within 3 years before enrolment and of low potential risk for recurrence. Exceptions include adequately resected non melanoma skin cancer (basal cell carcinoma of the skin or squamous cell carcinoma of the skin) and curatively treated in situ disease.
• 6. Persistent toxicities caused by previous anti-cancer therapy such as radiation, excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
• Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to Grade > 2 for at least 3 months prior to enrolment and managed with SoC treatment) which the investigator deems related to previous anti-cancer therapy, including (bu not limited to):
• (a) Chemotherapy-induced neuropathy.
• (b) Fatigue.
• (c) Residual toxicities from prior immunotherapy treatment: Grade 1 or Grade 2 endocrinopathies, which may include but are not limited to hypothyroidism/hyperthyroidism, Type I diabetes, hyperglycaemia, adrenal insufficiency, or adrenalitis; and skin hypopigmentation (vitiligo).
• Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss).
• 7. Spinal cord compression or clinically active CNS metastases (unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants). Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure). A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and the first dose of study intervention.
• 8. Significant third-space fluid retention (for example ascites or pleural effusion) not amenable to required repeated drainage.
• 9. Clinically significant corneal disease.
• 10. Uncontrolled infection requiring IV 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).
• 11 Known to have active tuberculosis infection (clinical evaluation that may include clinical history, physical examination, and radiographic findings, or tuberculosis testing in line with local practice).
• 12 Resting ECG with clinically abnormal findings.
• 13 Uncontrolled or significant cardiac disease including:
• (a) Mean QTcF prolongation > 470 msec (based on the average of screening triplicate 12 lead ECG determinations).
• (b) Myocardial infarction or uncontrolled/unstable angina within 6 months before the first dose of study intervention.
• (c) Congestive heart failure (New York Heart Association Class II to IV).
• (d) Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg).
• (e) Cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the investigator judgment with cardiologist consultation recommended.
• 14. Has severe pulmonary function compromise.
• 15. Any other medical conditions, including cardiac disease or psychological disorders, and/or substance abuse, that may, in the opinion of the investigator, interfere with the participant’s participation in the clinical study or evaluation of the clinical study results.