Inclusion Criteria:
* Written informed consent according to Swiss law and ICH GCP E6 regulations before registration and prior to any trial specific procedures;
* Histologically or cytologically confirmed diagnosis of NSCLC (adeno-, squamous-, large cell carcinoma or NSCLC not otherwise specified);
* Patients planned for systemic first-line therapy with a combination of a carboplatin-based doublet chemotherapy and a PD-1 / PD-L1 targeting immune checkpoint inhibitor;
* Patients not eligible for immune checkpoint inhibitor monotherapy irrespective of PD-L1 expression;
* Locally advanced unresectable stage III or metastatic stage IV disease (defined as TNM, according to 8th edition) not eligible for curative surgery and/or definitive (curative intended) chemoradiotherapy;
* No sensitizing EGFR mutation, METex14 skipping mutation, BRAF V600E mutation, ALK/ROS1/RET, NTRK1/2 gene rearrangements, HER2 mutations, amplifications detected in primary tumor or metastases;
* Have not received prior systemic treatment for their metastatic NSCLC. Patients who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for nonmetastatic disease are eligible if the therapy was completed at least 12 months prior to the diagnosis of metastatic disease;
* Patients with treated and stable CNS metastases are eligible, provided they meet the following criteria:
* No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed
* No stereotactic radiation or whole-brain radiation within 14 days prior to registration.
* Patients with known HIV-infection, who are at low risk of AIDS-related outcomes, are eligible, provided they meet the following criteria:
* CD4+ T-cell counts are ≥ 350 cells/ųL
* No history of AIDS-defining opportunistic infection within past 12 months
* Patients have been on antiretroviral therapy (ART) for \> 4 weeks before registration and have a HIV viral load \< 400 copies/mL;
* Patients with a prior malignancy and treated with curative intention are eligible if the treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence;
* Measurable disease per RECIST v1.134);
* Age ≥ 18 years;
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
* Adequate bone marrow function as per local guidelines;
* Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST and ALT ≤ 2.5 x ULN, or ≤ 5 x ULN under the assumption that abnormal values are a result of NSCLC;
* Adequate renal function defined by stable estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 (according to CKD-EPI formula);
* Women of childbearing potential must use highly effective contraception (see chapter 9.4), are not pregnant or lactating and agree not to become pregnant during trial treatment and until 6 months after the last dose of investigational drug. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential.
* Men agree not to donate sperm or to father a child during trial treatment and until 6 months after the last dose of investigational drug.
Exclusion Criteria:
* Plasma magnesium concentration \< 0.4 mmol/l or \> 1.2 mmol/L
* Treatment with any anti-cancer therapy within 21 days prior to registration (excluding hormonal therapy or anti-cancer surgery). Any previous anti-cancer therapy must have been administered with curative intent;
* Treatment with radiotherapy within 14 days prior to registration (except for local pain control);
* Patients planned for cisplatin-based chemo-immunotherapy;
* Treatment with any other experimental drug within 28 days of registration;
* Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia);
* Atrioventricular (AV) block of any degree unless being treated with cardiac pacemakers;
* Bradycardia \<40/min at steady state;
* Active chronic Hepatitis C or Hepatitis B infection or any uncontrolled active systemic infection, needing antibiotic treatment within 14 days before registration;
* Known history of tuberculosis, known history of relevant primary immunodeficiency, known history of allogeneic organ transplant, receipt of live attenuated vaccine within 28 days prior to registration;
* Diagnosis of myasthenia gravis;
* Concomitant or prior use of immunosuppressive medication within 28 days before registration, with the exceptions of:
* intranasal and inhaled corticosteroids
* systemic corticosteroids ≤ 10 mg/day of prednisone, or a dose equivalent corticosteroid,
* premedication for chemotherapy;
* Prior treatment with peroral or intravenous magnesium 14 days prior to registration;
* Patient not willing to stop the use of peroral magnesium treatment including over the counter or lifestyle products;
* Any concomitant drugs contraindicated for use with the trial drug according to the approved product information;
* Known hypersensitivity to any of the trial drugs;
* Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
