SAKK 17/18_ORIGIN Behandlung von einem fortgeschrittenen, nicht-kleinzelligen Lungenkrebs oder einem Mesotheliom mit Gemcitabin und Atezolizumab mit dem Ziel, eine Resistenz gegenüber einer Immuntherapie zu überwinden. Eine multizentrische einarmige offene Phase II Studie mit zwei Patientengruppen.

Drug: Gemcitabine;Drug: Atezolizumab

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

- Written informed consent according to Swiss law and ICH/GCP regulations before
registration and prior to any trial specific procedures including screening
procedures.

- For Cohort 1 (NSCLC): Patients with histologically- or cytologically- confirmed
squamous or non-squamous metastatic NSCLC stage IIIB-IV (based on TNM classification).
Patients must have experienced disease recurrence or progression during or after one
or more prior immunotherapy or chemo-immunotherapy regimen for metastatic disease.

- For Cohort 2 (MPM): Patients with histologically confirmed inoperable malignant
pleural mesothelioma (MPM; with or without metastasis; all histological subtypes are
eligible). Participants must have experienced disease recurrence or progression during
or after one or more prior systemic therapy regimen for advanced or metastatic
disease.

- Patients with treated and stable CNS metastases are eligible, if:

- Previous CNS-directed therapy has been completed at least 4 weeks prior to
treatment start

- No evidence of progression after completion of CNS-directed therapy as
ascertained by clinical examination and brain imaging (MRI or CT).

- Patients with known HIV-infection are eligible, if:

- CD4+ T-cell counts are = 350 cells/ul

- No history of AIDS-defining opportunistic infection within past 12 months

- Patient agrees to concomitant antiretroviral therapy (ART) if not currently on
ART, or is on ART for ? 4 weeks and has a HIV viral load ? 400 copies/ml.

- Patients with a previously treated malignancy are eligible if this is clinically
stable and does not require concurrent tumor-directed treatment.

Exception: patients suffering from prostate cancer under hormonal ablation therapy (hormone
sensitive disease) are eligible.

- Patients with measurable disease according to RECIST 1.1 or mRECIST 1.1.

- Availability of samples for translational research prior to treatment start. For the
tumor samples either archival or freshly prepared biopsy samples (cytology is not
allowed) are acceptable. Acceptable samples include core needle biopsies for deep
tumor tissue (three cores; or in case only two cores can be obtained, there has to be
tissue available in order to send 10 unstained slides considered by the local
pathologist to be representative of the tumor) or excisional, incisional, punch, or
forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.

- Age = 18 years.

- ECOG performance status 0-2.

- Adequate bone marrow function: absolute neutrophil count (ANC) = 1.5 x 109/L, platelet
count = 100 x 109/L, hemoglobin = 90 g/L or = 5.6 mmol/L.

- 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 for patients
with hepatic metastasis.

- Adequate renal function: estimated glomerular filtration rate (eGFR) = 40 ml/min/1.73
m2 (according to the Chronic Kidney Disease Epidemiology Collaboration) abbreviated
formula CKD-EPI formula).

- Women of childbearing potential, including women who had their last menstrual period
in the last 2 years, must use highly effective contraception, are not pregnant or
lactating and agree not to become pregnant during trial treatment and until 5 months
after the last dose of investigational drug. A negative serum or urine pregnancy test
before starting of trial treatment is required for all women of childbearing
potential.

- Men agree not to donate sperm or to father a child during trial treatment and until 5
months after the last dose of investigational drug (www.swissmedicinfo.ch).

- Patients consent to the mandatory translational research projects providing the
required samples.

Exclusion criteria

The presence of any one of the following exclusion criteria will lead to exclusion of the
participant:

- Symptomatic brain metastases indicative of active disease (defined as new and/or
progressive brain metastases at the time of treatment start [38]) or leptomeningeal
disease.

- Prior treatment with gemcitabine in combination with atezolizumab.

- NSCLC patients who progressed within the first 8 weeks from start of first line
treatment.

- NSCLC patients with activating EGFR or ALK mutations.

- Known unstable or unresolved surgical or chemotherapy-related toxicity that would
compromise trial treatment' duration.

- Concomitant or recent anti-cancer treatment (within 14 days prior to trial treatment
start) with any other experimental drug (enrollment in another clinical trial).

- Concomitant use of other anti-cancer drugs or radiotherapy (except for local pain
control).

- Cardiac disease NYHA 2 or greater.

- Major surgery within 1 month prior to trial treatment start.

- Known history of any uncontrolled active systemic infection requiring intravenous
(i.v.) antimicrobial treatment.

- Known history of tuberculosis, of primary immunodeficiency, of allogeneic tissue/solid
organ transplant, of receipt of live attenuated vaccine within 28 days prior to
treatment start.

- History of interstitial lung disease (ILD) or severe pneumonitis (other than chronic
obstructive pulmonary disease -COPD- exacerbation) that have required oral or i.v.
steroids, or uncontrolled pleural effusion.

- Concomitant use of systemic corticosteroids as premedication for chemotherapy.

- Concomitant or prior use of systemic immunosuppressive medication (such as interferon,
methotrexate) within 28 days prior to trial treatment start, with the exceptions local
(i.e. intranasal, inhaled and topical) corticosteroids.

- Any concomitant drugs contraindicated for use with the trial drugs according to the
approved product information or to the Investigator' Brochure.

- Known or suspected hypersensitivity to trial drug(s) or to any component of the trial
drug(s).

- 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.