Studies

Populatie: 

• ES-SCLC patiënten 
• 1 voorgaande behandeling (met een chemovrij-interval van minstens 30 dagen).
• Chemo voor LD moet minstens 6 maanden geleden zijn. 
• Hersenmeta’s moeten asymtomatisch of behandeld zijn

Arm 6 Rilvegostomig + platinum doublet chemotherapy (Q3W)  *4 Cycles neo-adjuvant + Rilvegostomig (Q3W)  *16 Cycles adjuvant

Arm7: Rilvegostomig + Dato-Dxd + single agent platinum chemotherapy (Q3W) *4 Cycles neoadjuvant +  Rilvegostomig (Q3W)  *16 Cycles adjuvant

• Patients should have resectable (Stage II to Stage IIIA disease.For subjects with N2 disease, only those with 1 single nodal station ≤ 3 cm are eligible) and be candidate for lobectomy, sleeve resection, or bilobectomy at the time of screening
• No prior exposure to immune-mediated therapy
• excl: Patients who require preoperative radiotherapy treatment as part of their care plan.
• Testing for EGFR/ALK is mandatory for subjects with adenocarcinoma or never smokers with squamous histology
• Availability of pretreatment tumor tissue biopsy

• The patient must have a pathologically or cytologically confirmed Stage IV NSCLC that could be treated with pembrolizumab alone or combined with carboplatin/pemetrexed or paclitaxel. 
• The patient must be treatment naïve for stage IV NSCLC at the time of study enrolment. Patients having received, at least 6 months before D1, platinum derivatives adjuvant after (i) surgery or (ii) concomitant chemotherapy-radiotherapy for unresectable locally advanced NSCLC are eligible.
• The patient must have a resting oxygen saturation of at least 90%, a FEV1 ≥50% of predicted values as determined by spirometry and a DLCO of at least 50%. 
• Patients who have received prior radiotherapy within 4 weeks prior to the planned day for the first study treatment administration will be excluded (D1), except palliative radiotherapy (2 weeks). Patients must have recovered from all radiation-related toxicities, not require corticosteroids (see criterion 24) and not have had radiation pneumonitis >grade 2. 
• Patients using oral corticosteroids within 4 weeks prior to the planned day for the first study treatment administration (D1) above daily dose of 10 mg or any single dose of 16 mg are not eligible. Patients receiving inhaled or topical corticosteroids are eligible. 

• Histologically or cytologically documented NSCLC
• stage IIIB or IIIC disease not amenable for surgical resection or defenitive chemoradiation, or Stage IV metastatic NSCLC disease 
• no prior chemotherapy or other systemic therapy for first-line Stage IIIB, IIIC or IV NSCLC.
•  Lacks sensitizing EGFR mutation (e.g., exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), ALK and ROS1 rearrangement. Has no known genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with locally-approved therapies.
• FFPE tumour sample collected ≤ 3 months prior to signing of informed consent, ie, the start of screening.

• Gemetastaseerde NSCLC met positieve PD-L1 status (≥1%)
• Tweede- of derdelijns: MOETEN reeds platinumchemo én PDL1 inhibitor gekregen hebben (minstens 6 weken waarop respons ten minste SD) (samen of sequentieel) voor stadium IV
• Progressie op laatste therapie
• Gekende hersenmeta’s moeten stabiel of asymptomatisch zijn. Behandelde hersenmeta’s moeten minstens 28 dagen stabiel zijn op 2 opeenvolgende scans. 
• ECOG score 1 of 0

Inclusion criteria:

• Patients with histologically or cytologically squamous or non-squamous documented NSCLC, metastatic stage at study entry, not eligible for definite surgery or radiation, without EGFR, ALK and ROS1 gene alterations eligible for targeted therapy
• Patients who progressed after ≥ 24 weeks of first-line CT-ICI, including ≥12 weeks of anti-PD(L)1 as monotherapy or in combination with another ICI prior to randomization(i.e.; ICI secondary resistance); a radiological tumor assessment by the Investigator at 24 weeks (± 2 weeks) after the start of ICI is needed to exclude PD; induction treatment with first-line CT-ICI should contain at least 2 cycles of platinum-based CT except if contraindication to platinum

Exclusion criteria: 

• Patients with PD during induction first-line CT-ICI (to exclude hyper progression and fast progression to CT-ICI) or with PD within 24 weeks of ICI; chemotherapy, other cytotoxic agent or antiangiogenics in combination with ICI within 12 weeks prior to randomization are not authorized; patients who stopped ICI due to toxicity or other reason than PD are not eligible
• Patients with brain metastasis or previously treated brain metastasis, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease
• Patients with interstitial lung disease or active non-infectious pneumonitis

• Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R mutation, and/or T790M.
• EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with osimertinib as the most recent therapy
• Participants must be chemotherapy and immunotherapy (i.e., PD-1 inhibitor, PD-L1 inhibitor, T-lymphocyte-associated protein 4 inhibitor) naïve in the metastatic setting
• clearance ≥ 45 mL/min

• Stadium IV AdenoCA, niet voordien behandeld, met EGFR ex20ins mutatie

• locally advanced non-squamous NSCLC,
• activating HER2 mutation 
• No prior systemic therapy for locally advanced or metastatic disease.
• No prior treatment with a HER2 ex20ins-targeted therapy (eg poziotinib, trastuzumab deruxtecan).
• Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the start of screening
• Participants with treated brain metastases that are asymptomatic at screening are eligible if all of the following criteria are met: 
  • There is no evidence of progression (new or enlarging brain metastases) for at least 6 weeks after CNS-directed treatment
  • Participants must be off or receiving low-dose of corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to the first dose 

• Documented history of the KRAS G12C mutation
• Documented history of PD-L1 expression: 
  • For Cohort A1, PD-L1 tumor cell expression 1% is required to be eligible. 
  • For Cohort A2, PD-L1 tumor cell expression 1% is required to be eligible, unless detailed below. 
  • For Cohort B, PD-L1 tumor cell expression is not required to be eligible
     
• Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study
• No prior systemic treatment for advanced unresectable or metastatic NSCLC
• Measurable disease, as defined by RECIST v1.1
• History of leptomeningeal disease is excluded
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases are excluded

Populatie:

• Stadium IIIc of IV NSCLC, KRAS G12C positief en gekende KEAP status
• patiënten die reeds chemo- en immunotherapie kregen (max 3 voorgaande lijnen). 
• Hersenmeta’s moeten behandeld en stabiel en asymptomatisch zijn. 
• Verplicht tumorstaal op te sturen tijdens screening.

Inclusion criteria:

• 18-80 years of age
• Have had a chronic cough for at least 1 year
• Have seen a doctor and received prescribed or over-the-counter medicines but without improvement
• 24-hour cough frequency of ≥20 per hour

Exclusion criteria:

• Current smoker/vaper or individuals who have given up smoking within the past 6 months
• Body Mass Index of ≥40 kg/m2
• Supine systolic blood pressure >150 mmHg or <85 mmHg, a supine diastolic blood pressure >95 mmHg or <40 mmHg, or a pulse rate ≥100 or <40 beats per minute
• Diagnosis of COPD or other pulmonary diseases

Excluded medications:

• Opioids (e.g. morphine)
• Gabapentin (tricyclics)
• Chronic, systemic corticosteroid use
• Inhalers
• Medication to aid sleep
• Medication to regulate blood pressure (e.g. Losartan)
• Cough suppressant (e.g. paracodine)
• Speech therapy

• Adult participants ≥ 18 years old at the time of signing the ICF.
• Patients hospitalised with viral lung infection. Note: Suspected viral aetiology is
• acceptable to meet this criterion.
• Hypoxaemia requiring treatment with supplemental O2, consistent with WHO Clinical
• Progression Scale for Disease Progression score of 5 and 6.
• Note: Hypoxemia is defined as SpO2 ≤ 94% on room air at screening, or documented
• SpO2 ≤ 94% prior to initiation of oxygen therapy. Patients receiving oxygen > 6 L/min
• or non-invasive ventilation will be considered to have met this inclusion criterion
• regardless of SpO2 levels.
• ≤ 36 hours since admission to hospital.
• ≤ 14 days since onset of respiratory viral infection symptoms.