Ovel Immunotherapy strategies for advanced Triple negative breast Cancer (TNBC) patients: TONIC-3 trial

Phase 1

Recruiting

Conditions: advanced TNBC, eg. irresectable recurrent disease or metastatic disease
MedDRA version: 23.0Level: LLTClassification code: 10084066Term: Triple negative breast cancer metastatic Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-507875-23-00

Lead Sponsor: Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

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, 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, Calculated (Cockcroft-Gault) or measured creatinine clearance > 40 mL/min, Signed informed consent, 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), Metastatic lesion accessible for histological biopsy (Mandatory biopsies: baseline, after 1 cycle of treatment. Optional biopsies: 12-weeks, at progression)., 18 years or older, WHO performance status of 0 or 1, Maximum of three lines of chemotherapy (including antibody-drug conjugates and PARP-inhibitors) for metastatic disease and with evidence of progression of disease., Measurable or evaluable disease according to RECIST 1.1, 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., 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/

Exclusion Criteria

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, Active other cancer, 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, Sign of active TB, Positive HIV test at screening, Positive EBV viral capsid antigen immunoglobulin M (IgM) test at screening, History of uncontrolled serious medical or psychiatric illness, Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, 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 t