CCTG IND.241

Liquid-biopsy Informed Platform Trial to Evaluate CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer

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Population: ER+, HER2- Metastatic Breast Cancer

Line of therapy: 2L+

Intervention: Substudy B: RP-6306 -- Substudy C: NIRAPARIB

Key Inclusion Criteria

1. Patients must have histologically and/or cytologically confirmed, advanced / metastatic breast cancer, ER ≥10% and not HER2 overexpressing/amplified as per ASCO/CAP criteria. Patients with locally advanced or inflammatory disease without distant metastases that is potentially resectable or treatable with curative intent are not eligible.

2. All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block

3. Patients must have had objective disease progression demonstrated on (defined as while taking or within 8 weeks of the last dose) first line CDK4/6i + ET for MBC. Patients who discontinued CDK4/6i + ET without disease progression more than 8 weeks prior to objective disease progression (toxicity, patient request) are not eligible. Patients must have received at least 24 weeks of first line CDK4/6i + ET therapy. Patients with one subsequent line of endocrine-based therapy may only enroll in 3rd line substudies .

4. Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative).

5. All patients must have measurable disease as defined by RECIST 1.1.

6. Patients must be ≥ 18 years of age.

7. Patients must have an ECOG performance status 0 or 1

8. Patients must have a life expectancy ≥ 3 months

   
   

Key Exclusion Criteria

1. Patients with a history of other malignancies, including Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML) except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other malignancies curatively treated with no evidence of disease for ˃ 2 years and which do not require ongoing treatment.

2. Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to protocol.

3. Patients with recent clinically significant cardiac disease

4. All patients should have a LVEF ≥ 50%.

5. Patients with HER2 positive breast cancer (based on the most recent assessment, according to ASCO/CAP criteria).

6. History of hypersensitivity to any of the study drugs or their components.

7. Patients may not receive concurrent treatment with other anti-cancer therapy (other than bone-targeted therapy, if already taking and stable) or investigational agents while on protocol therapy.

8. Patients with prior allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

Sponsor: CCTG

CRP Contact:  wagdy.rezk@ladydavis.ca

514-340-8222 ext. 25728

CRP PI: Dr. P. Fallah

Status: Open to accrual