| Eligibility |
Inclusion Criteria:
- Histological or cytological proof of advanced breast cancer (M1) or advanced
gynaecological cancer (cervix (M1, FIGO IVA/IVB), ovarian (only after recurrence on
carboplatin and/or paclitaxel) stage 4 cervical or endometrial (T3-T4, FIGO IVA/IVB)
cancer) pre-treated with maximally one line of systemic chemotherapy in the advanced
setting and any line of hormonal therapy for advanced disease and potentially
benefitting from carboplatin-cyclophosphamide and atezolizumab. (prior (neo-)adjuvant
chemotherapy is accepted and does not count as one line, since administered in early
stage disease);
- Men and women >= 18 years;
- Able and willing to give written informed consent;
- WHO performance status of 0 or 1;
- Life expectancy >= 3 months, allowing adequate follow up of toxicity evaluation and
antitumor activity;
- Minimal acceptable safety laboratory values
Exclusion Criteria:
- Any treatment with investigational drugs within 28 days prior to receiving the first
dose of investigational treatment; or 21 days for standard (neo-)adjuvant
chemotherapy, hormonal and immunotherapy;
- Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies.
- Women who have a positive pregnancy test (urine or serum) and/or who ware breast
feeding;
- Unreliable contraceptive methods. Women and men enrolled in this trial must agree to
use a reliable contraceptive method throughout the study (adequate contraceptive
methods are: oral, injected or implanted hormonal methods, intra-uterine devices or
systems, condom or other barrier contraceptive measures, sterilization and true
abstinence);
- Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2
type patients;
- Positive test for HIV
- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HbsAg]
test at screening) or active hepatitis C Patients with past hepatitis B virus (HBV)
infection or resolved HBV infection (defined as having a negative HBsAg test and a
positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase
chain reaction (PCR) is negative for HCV RN
- Active tuberculosis
- Receipt of a live, attenuated vaccine within 28 days prior to enrolment or
anticipation that such a live, attenuated vaccine will be required during the study
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
anti-CTLA-4 (like Ipilimumab), anti-PD-1 (like pemprolizumab), or anti-PD-L1
therapeutic antibodies (like atezolizumab).
- Treatment with systemic immunostimulatory agents (including but not limited to
interferons or IL-2) within 28 days or five half-lives of the drug (whichever is
shorter) prior to enrolment;
- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
within 28 days prior to enrolment, or anticipated requirement for systemic
immunosuppressive medications during the trial
- Patients who have received acute, low-dose, systemic immunosuppressant medications
(e.g., one-time dose of dexamethasone for nausea) may be enrolled in the study. The
use of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension,
and low-dose supplemental corticosteroids for adrenocortical insufficiency are
allowed;
- Patients with known alcoholism, drug addiction and/or psychiatric of physiological
condition which in the opinion of the investigator would impair study compliance;
- Recent myocardial infarction (<six months prior to enrolment) or unstable angina;
- New York Heart Association Class II or greater congestive heart failure. If cardiac
failure is suspected: LVEF by MUGA or ultrasound must be = 50% and should be performed
within 28 days prior to enrolment.
- Symptomatic brain metastases. If adequately treated with resection and/or irradiation
and patients are at least four weeks completely free of symptoms of these metastases
and without medication related to these metastases patients could be eligible if all
other in-and exclusion criteria are obeyed.
- Known leptomeningeal metastases; History of autoimmune disease including, but not
limited to, systemic lupus erythematosus, rheumatoid arthritis, imflammatory bowel
disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple
sclerosis, vasculitis or glomerulonephritis; Patients with a history of
autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may
be eligible for this study;
- Prior allogenic stem cell or solid organ transplantation;
- History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with
organizing pneumonia) or evidence of active pneumonitis on screening chest computed
tomography scan.
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Severe infections within 28 days prior to enrolment, including, but not limited to,
hospitalization for complications of infection, bacteraemia, or severe pneumonia;
- Signs or symptoms of significant infection within 2 weeks prior to enrolment;
- Received oral or IV antibiotics within 2 weeks prior to enrolment
- Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease) are eligible;
- History of stroke or transient ischemic attack (TIA) within 6 months prior to
enrolment;
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to enrolment or anticipation of need for major surgical procedure during the
course of the study
- Any medical condition not yet specified above that is considered to possibly, probably
or definitely interfere with study procedures, including adequate follow-up and
compliance and/or would jeopardize safe treatment.
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