Atezolizumab for Triple-negative breast cancer (metastatic)

Inclusion criteria

• {"criterion_text":"- Metastatic or incurable locally advanced triple negative breast cancer with confirmation of ER and HER2 negativity (ER <10% and HER2 IHC 0, 1+ or 2+ in the absence of amplification as determined by in situ hybridization, independent of progesterone receptor expression) on a histological biopsy of a metastatic lesion"}
• {"criterion_text":"- Bilirubin < 1.5 x upper limit of the normal range (ULN)(except for participants with Gilbert Syndrome <3x ULN); alkaline phosphatase < 2.5 x ULN (< 5 x ULN in case of liver metastases, and < 7 x ULN N22TON, version 1.0 dd 21 July 2023 10 in case of bone metastases); transaminases (ASAT/ALAT) < 3 x ULN (and < 5 x ULN in case of liver metastases), LDH < 2xULN"}
• {"criterion_text":"- Calculated (Cockcroft-Gault) or measured creatinine clearance > 40 mL/min"}
• {"criterion_text":"- Signed informed consent"}
• {"criterion_text":"- Patients with PD-L1 negative disease determined using the Combined Positivity Score (CPS<10) (Dako 22C3 immunohistochemistry) OR previously treated with anti-PD(L)1 in the (neo)adjuvant or metastatic setting (irrespective of PD-L1 status)"}
• {"criterion_text":"- Metastatic lesion accessible for histological biopsy (Mandatory biopsies: baseline, after 1 cycle of treatment. Optional biopsies: 12-weeks, at progression)."}
• {"criterion_text":"- 18 years or older"}
• {"criterion_text":"- WHO performance status of 0 or 1"}
• {"criterion_text":"- Maximum of three lines of chemotherapy (including antibody-drug conjugates and PARP-inhibitors) for metastatic disease and with evidence of progression of disease."}
• {"criterion_text":"- Measurable or evaluable disease according to RECIST 1.1"}
• {"criterion_text":"- Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year. This does not apply to patients with de novo metastatic disease or patients who did not receive (neo)adjuvant chemotherapy."}
• {"criterion_text":"- WBC ≥ 2.0x109/L, ANC ≥ 1.5 x 109/L(without G-CSF use in last 4 weeks), platelets ≥100 x 109/L, Hemoglobin ≥ 5.0 mmol/L"}

Exclusion criteria

• {"criterion_text":"- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris"}
• {"criterion_text":"- Active other cancer"}
• {"criterion_text":"- Positive test for hepatitis B surface virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Specified by: positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: negative total hepatitis B core antibody (HBcAb), positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL. The HBV DNA test will be performed only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. Specific for hepatitis C screening: positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test"}
• {"criterion_text":"- Sign of active TB"}
• {"criterion_text":"- Positive HIV test at screening"}
• {"criterion_text":"- Positive EBV viral capsid antigen immunoglobulin M (IgM) test at screening"}
• {"criterion_text":"- History of uncontrolled serious medical or psychiatric illness"}
• {"criterion_text":"- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- Current pregnancy pregnancy or breastfeeding. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception: Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 90 days after the final dose of tiragolumab, 5 months after the final dose of atezolizumab. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. (The definition of childbearing potential may be adapted for alignment with local guidelines or regulations). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period, for 90 days after the final dose of tiragolumab. Men must refrain from donating sperm during this same period. With a pregnant female partner, men must remain abstinent or use a condom during the treatment period for 90 days after the final dose of tiragolumab to avoid exposing the embryo. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form."}
• {"criterion_text":"- Symptomatic brain metastases, subjects with asymptomatic brain metastases are eligible. Subjects who received prior treatment for brain metastases should be free of progression on magnetic resonance imaging (MRI) for at least 4 weeks after treatment is completed and prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration"}
• {"criterion_text":"- History of leptomeningeal disease localization"}
• {"criterion_text":"- History of having received other anticancer therapies within 2 weeks of start of the study drug"}
• {"criterion_text":"- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins"}
• {"criterion_text":"- Known hypersensititivy to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation"}
• {"criterion_text":"- History of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (>10 mg daily prednisone equivalents) or chronic infections. Subjects with vitiligo, diabetes mellitus type I, psoriasis not requiring systemic treatment or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement, Sjøgren’s syndrome or conditions not expected to recur in the absence of an external trigger will not be excluded from the study. Adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease"}
• {"criterion_text":"- Prior treatment with an anti-CTLA4 or anti-TIGIT antibody"}
• {"criterion_text":"- Administration of live vaccine within 30 days of planned start of study therapy."}

Primary endpoints

• {"endpoint_text":"- Progression-free survival rate as measured by the proportion of patients free of progression after 12-weeks of treatment (PFS: time from administration of first treatment to tumor progression or death from any cause) according to RECIST1.1","definition_or_measurement_approach":"PFS: time from administration of first treatment to tumor progression or death from any cause; assessed according to RECIST1.1; rate measured as proportion free of progression after 12 weeks"}
• {"endpoint_text":"- Adverse events as measured according to CTCAE v5.0 and immune-related toxicity","definition_or_measurement_approach":"Adverse events graded and measured according to CTCAE v5.0; includes immune-related toxicity assessments"}

Secondary endpoints

• {"endpoint_text":"- Response as measured by the objective response rate (ORR: complete responses or partial responses) according to iRECIST and RECIST1.1","definition_or_measurement_approach":"ORR measured as proportion of complete or partial responses; evaluated by iRECIST and RECIST1.1"}
• {"endpoint_text":"- Clinical benefit as measured by the clinical benefit rate (CBR) according to iRECIST and RECIST1.1","definition_or_measurement_approach":"CBR measured according to iRECIST and RECIST1.1"}
• {"endpoint_text":"- PFS measured by time to event","definition_or_measurement_approach":"Progression-free survival measured as time-to-event (time from treatment start to progression or death)"}
• {"endpoint_text":"- Overall survival (OS: time from therapy initiation to death from any cause)","definition_or_measurement_approach":"Overall survival measured as time from therapy initiation to death from any cause"}

Netherlands

Earliest CTIS Part Ii Submission Date

01-12-2023

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

164

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands