A phase 1b, dose finding, open label study of the safety and tolerability of carboplatin-cyclophosphamide combined with atezolizumab, an antibody that targets programmed death ligand 1 (PD-L1), in patients with advanced breast cancer, ovarian, cervical and endometrial cancer.

The Dutch Triple B study is a phase IIB study in advanced TNBC where we test
the hypothesis that patients with BRCA-like tumors will benefit from a
platinum-alkylating drug combination as first line treatment while patients
with non-BRCA like tumors will benefit from a taxane. Besides that, we evaluate
whether addition of bevacizumab to either drug schedule can further improve
outcome and whether plasma VEGFR-2 levels can predict for benefit of
bevacizumab. Because one of the co-primary endpoints of the Triple B study in
the meanwhile has been answered by outcomes of the Meridian trial, namely that
VEGFR-2 fails as a reliable biomarker for bevacizumab benefit, and because
atezolizumab shows promising activity in this particular patient group, we want
to replace bevacizumab by atezolizumab in this study.

To determine a safe dose combination of carboplatin-cyclophosphamide combined
with atezolizumab fixed dose in advanced breast cancer and gynaecologic cancer
(ovarian, cervical and endometrial cancer).

This is a single centre, 3+3, dose finding, open label, phase 1b clinical study
of carboplatin and cyclophosphamide, in combination with atezolizumab. The
starting dose is carboplatin AUC 5mg/ml*min, cyclophosphamide 600mg/m2 and
atezolizumab 840 mg, all administered intravenously (see table 1). One cycle is
28 days. On day 1 carboplatin, cyclophosphamide and atezolizumab will be
administered. On day 15 atezolizumab only will be administered. After 6 cycles
treatment can be continued with atezolizumab monotherapy, every three weeks as
long as the patient experiences clinical benefit in the opinion of the
investigator.
Patients will be treated until loss of clinical benefit, unacceptable
toxicities, or withdrawal of consent. It is expected that 6-12 patients will be
enrolled, depending on safety issues observed.

carboplatin AUC 5mg/ml*min, cyclophosphamide 600mg/m2 and atezolizumab 840 mg,
all administered intravenously.
One cycle is 28 days.
On day 1 carboplatin, cyclophosphamide and atezolizumab will be administered.
On day 15 atezolizumab only will be administered.
After stop combination therapy patients can continue treatment with
atezolizumab monotherapy, 1200 mg flat dose, every three weeks as long as the
patient experiences clinical benefit in the opinion of the investigator

Patients are at risk for development of carboplatin-,
cyclophosphamide-,atezolizumab-related side effects.