Atezolizumab and bevacizumab are a type of drug called a monoclonal antibody. Antibodies are
proteins that are naturally found in the blood stream that fight infections. A monoclonal
antibody is a special kind of antibody that is created in a laboratory that seeks out
specific proteins in the body that may be involved in cancers to stop tumor growth.
When tumor cells start to die, broken down pieces of the tumor's DNA gets released into the
blood stream, called circulating tumor DNA (ctDNA). Looking at ctDNA may be useful in
determining whether the cancer is responding to treatment.
The purpose of this research study is to see whether looking at tumor DNA circulating in the
bloodstream can help to determine which patients may respond to atezolizumab and bevacizumab
and whether this drug combination is useful, when given as a maintenance treatment for
patients with TP53 mutant ovarian, fallopian tube, or primary peritoneal cancer.
Inclusion Criteria:
Pre-screening:
- Patients must have histologically confirmed TP53-mutant high grade serous or high
grade endometrioid ovarian, fallopian tube, primary peritoneal cancer.
- Ability to understand and the willingness to sign a written Pre-screening Informed
consent document.
- Patients must be receiving standard therapy for recurrent disease and have completed 3
cycles of platinum-based chemotherapy, with clinical benefit (in opinion of
investigator). Patients with stable disease (in opinion of investigator) after 3
cycles of chemotherapy will also be eligible for pre-screening. There is no limitation
on the number of prior lines of therapy. May have received prior PARP-inhibitor
therapy or prior bevacizumab or biosimilar.
- Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be
available.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Patients must have a life expectancy ≥16 weeks
Main Study:
- Patients must have histologically confirmed TP53-mutant high grade serous or high
grade endometrioid ovarian, fallopian tube, primary peritoneal cancer.
- Must have completed standard therapy for recurrent disease including at least 4 cycles
of platinum-based chemotherapy with no clinical and radiographic evidence of disease
progression on the post-treatment scan or a rising CA-125 level, following completion
of standard therapy. Patients with stable disease and in response (as per
Investigators opinion) following completion of chemotherapy will also be eligible for
this study. There is no limitation on the number of prior lines of therapy.
- Following completion of platinum-based chemotherapy, patients must have residual
disease detectable by TP53 ctDNA
- May have received prior PARP-inhibitor therapy or prior bevacizumab.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Patients must have a life expectancy ≥16 weeks
- Patients must have normal organ and marrow function
- Ongoing prior toxicities related to previous treatments must be recovered to ≤ grade 2
at the time of registration
- Ability to understand and the willingness to sign a written informed consent document.
- Patients must receive first dose of study treatment within 8 weeks after their last
dose of platinum based chemotherapy (last dose is the day of the last infusion)
- Postmenopausal or evidence of non-childbearing status for women of childbearing
potential. Female patients of childbearing potential should use highly effective
contraception and take active measures to avoid pregnancy while undergoing
atezolizumab treatment and for at least 5 months after the last dose.
- Willing and able to comply with the protocol for the duration of the study including
undergoing treatment and scheduled visits and examinations
- Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be
available.
- Pre-treatment CA-125 measurements must meet specific criterion
Exclusion Criteria:
Pre-screening:
- History of severe allergic reactions attributed to compounds of similar chemical or
biologic composition to bevacizumab, or atezolizumab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
severe infection, symptomatic congestive heart failure, or psychiatric illness/social
situations that (in the opinion of Investigator) would limit compliance with study
requirements.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 6 months prior to day 1.
Main Study:
- Patients who are receiving any other investigational agents or on-going chemotherapy.
- History of severe allergic reactions attributed to compounds of similar chemical or
biologic composition to bevacizumab, or atezolizumab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
severe infection, symptomatic congestive heart failure, or psychiatric illness/social
situations that (in the opinion of Investigator) would limit compliance with study
requirements.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 6 months prior to day 1.
- Invasive procedures defined as follows:
- Major surgical procedure or significant traumatic injury within 28 days prior to
Day 1 therapy, or open biopsy within 28 days prior to Day 1 therapy
- Anticipation of need for major surgical procedures during the course of the study
- Significant vascular disease within 6 months prior to Day 1
- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because of the possible increased risk of bleeding
if treatment with antiangiogenic agents is provided.
- Inadequately controlled hypertension, history of cerebrovascular accident, myocardial
infarction or unstable angina, serious or inadequately controlled cardiac arrhythmia
within 6 months.
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies.
- Resting ECG with QTcF > 470 msec or family history of long QT syndrome.
- History of bowel obstruction within 28 days from proposed start of treatment.
- History or evidence of arterial thrombotic or hemorrhagic disorders within 3 months
before proposed start of treatment, non-healing wound, ulcer, or bone fracture.
- Known active HIV or hepatitis B or C infection
- Other malignancy within the last 3 years except: adequately treated non-melanoma skin
cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ
(DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including
lymphomas (without bone marrow involvement) curatively treated with no evidence of
disease for ≥5 years. Patients with a history of localised breast cancer may be
eligible, provided they completed their adjuvant chemotherapy more than three years
prior to registration, and that the patient remains free of recurrent or metastatic
disease
- Patients should be excluded if they have had prior treatment with anti-CTLA-4 antibody
or any other antibody or drug specifically targeting T-cell co-stimulation. Previous
treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 is not allowed.
- The patient has experienced any of the following:
- The patient has radiographic evidence of cavitating pulmonary lesion(s).
- The patient has tumour invading or encasing any major blood vessels.
- The patient has evidence of tumour invading the GI tract (esophagus, stomach,
small or large bowel, rectum or anus), or any evidence of endotracheal or
endobronchial tumour within 28 days before the first dose of study treatment
- Patient with extensive pelvic mass at risk of fistulization, or history
- Active peptic ulcer disease within 28 days before the first dose of study
treatment.
- Inflammatory bowel disease (including ulcerative colitis and Crohn's disease),
diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
- Malabsorption syndrome
- Other disorders associated with a high risk of fistula formation including PEG
tube placement.
- Clinically significant gastrointestinal bleeding within 6 months before the first dose
of study treatment
- Administration of a live vaccine within 4 weeks prior to start of protocol therapy.
- Patients with diagnosis of immunodeficiency or who are receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of trial treatment. The following are exceptions to this exclusion
criteria: intranasal, inhaled, topical steroids, or local steroids injections (e.g.
intra-articular injection); systemic corticosteroids at physiologic dose not to exceed
10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity
reactions (eg, CT scan premedication).
- History of autoimmune disease, such as, but not restricted to: rheumatoid arthritis,
inflammatory bowel disease, systemic lupus erythematous, ankylosing spondylitis,
scleroderma, or multiple sclerosis requiring treatment within the last two years.
Patients with vitiligo or diabetes are not excluded. Replacement therapy (e.g.
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Patients with recent history of thyroiditis.
