Brief Title
SAKK 17/18 (ORIGIN) MPM & NSCLC >1st Line Gemci & Atezo Ph II
Official Title
Overcoming Resistance to Immunotherapy Combining Gemcitabine With Atezolizumab in Advanced NSCLC and Mesothelioma Progressing Under Immune-checkpoint Inhibitors or Gemcitabine. A Multicenter, Single-arm, Open Label Phase II Trial With Two Cohorts
Brief Summary
A significant number of patients with malignant pleural mesothelioma (MPM) and non-small cell
lung cancer (NSCLC) are not cured with available treatments and will eventually relapse.
After relapse treatment options are limited. Preclinical in vitro studies have demonstrated a
synergism of immunotherapy with PD(L)1-targeting monoclonal antibodies and gemcitabine and
ongoing clinical studies showed encouraging results.
The main objective of this trial is to determine the efficacy of chemotherapy (gemcitabine)
combined with immunotherapy (atezolizumab) in patients with progressive NSCLC and MPM.
The trial treatments will be continued for max. 2 years or until discontinuation criteria are
met. The follow-up phase will last up to 5 years from treatment start.
Detailed Description
The trial combines two (Gemcitabine and Atezolizumab). Gemcitabine, alone or in combination
regimens is a standard of care for several solid tumors, such as advanced or metastatic
NSCLC. It is also used in an off-label setting for pre-treated MPM or naïve MPM in
combination with platin-chemotherapy.
Atezolizumab is approved in the United States, European Union and in Switzerland for the
treatment of NSCLC, urothelial carcinoma, small cell lung cancer (SCLC) and triple-negative
breast cancer (TNBC) patients.
A significant number of patients with malignant pleural mesothelioma (MPM) and non-small cell
lung cancer (NSCLC) are not cured with available treatments and will eventually relapse.
After relapse treatment options are limited. Preclinical in vitro studies have demonstrated a
synergism of immunotherapy with PD(L)1-targeting monoclonal antibodies and gemcitabine
administered in different tumors models and ongoing clinical studies showed encouraging
results. This may represent a safe and effective therapy for patients who relapsed or did not
respond to standard therapies.
Patients will be treated with gemcitabine (1000 mg/m2 i.v. on day 1 and day 8 of each cycle,
(every 3 weeks) and with atezolizumab (1200 mg i.v. on day 1 of each cycle, (every 3 weeks).
The trial treatments will be continued for max. 2 years or until discontinuation criteria are
met. The follow-up phase will last up to 5 years from treatment start.
The main objective of this trial is to determine the efficacy of chemotherapy (gemcitabine)
combined with immunotherapy (atezolizumab) in patients with progressive NSCLC and MPM.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Primary endpoint for cohort 1: Objective response rate (ORR) according to RECIST 1.1
Secondary Outcome
For cohort 1 (NSCLC): Duration of response (DoR) according to RECIST 1.1
Condition
Malignant Pleural Mesothelioma
Intervention
Gemcitabine
Study Arms / Comparison Groups
NSCLC (cohort 1) and inoperable MPM (cohort 2)
Description: Cohort 1 consists of NSCLC patients. Cohort 2 consists of MPM patients. Patients will be treated with gemcitabine at the dose of 1000 mg/m2 i.v. on day 1 and day 8 of each cycle (every 3 weeks) and with atezolizumab at the dose of 1200 mg i.v. on day 1 of each cycle (every 3 weeks). The trial treatments will be continued for max. 2 years or until discontinuation criteria are met (see Ch. 9.3), whichever occurs first. The follow-up phase will last up to 5 years from treatment start.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
67
Start Date
December 2020
Completion Date
December 2025
Primary Completion Date
April 2025
Eligibility Criteria
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 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/ųl
- 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 (minimum three cores) or excisional, incisional, punch, or forceps
biopsies for cutaneous, subcutaneous, or mucosal lesions. See Ch. 12 and 17 for
further details.
- 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 treatment (within 30 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 corticosteroids as premedication for chemotherapy.
- Concomitant or prior use of immunosuppressive medication (such as interferon,
methotrexate) within 28 days prior to trial treatment start, with the exceptions of
intranasal and inhaled 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Alessandra Curioni Fontecedro, MD, +41 31 389 91 91, [email protected]
Location Countries
Switzerland
Location Countries
Switzerland
Administrative Informations
NCT ID
NCT04480372
Organization ID
SAKK 17/18
Responsible Party
Sponsor
Study Sponsor
Swiss Group for Clinical Cancer Research
Study Sponsor
Alessandra Curioni Fontecedro, MD, Study Chair, University of Zurich
Verification Date
November 2020