CAAA603D12101 (JCP150)

An Interventional, Open-Label, Randomized, Multicenter Phase 3 Study of PF-07220060 Plus Fulvestrant Compared To Investigator`s Choice of Therapy in Participants Over 18 Years of Age with Hormone Receptor-Positive, HER2-Negative Advanced/Metastatic Breast

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Population: ER+, HER2- Metastatic Breast Cancer

Line of therapy: 2L - After Progression on Previous Endocrine Therapy in Combination With a CDK4/​6 Inhibitor

Intervention: [177Lu]Lu-NeoB + Capecitabine (Imaging Drug: [68Ga]Ga-NeoB)

Key Inclusion Criteria

1. Histologically and/or cytologically documented diagnosis of ER+ breast cancer (ER expression >10% of tumor cell nuclei stain, regardless of PgR expression)

2. HER2- breast cancer defined as a negative in situ hybridization test (ISH) or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative ISH

3. No more than three prior endocrine therapy/ies (single agent or in combination with targeted therapy) regimen/s in the metastatic setting of which at least one included endocrine therapy in combination with a CDK4/6i. In addition:

   • if confirmed presence of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the participant may also have received a PARP inhibitor-based therapy.

   • if HER2-low breast cancer, the participant may also have received Enhertu®

4. Metastatic breast cancer with radiologically confirmed progression of disease after the most recent therapy

5. Measurable disease as per RECIST 1.1.

6. At least one target lesion with [68Ga]Ga-NeoB uptake above the liver at PET/CT or PET/MRI, as per local reading.

7. ECOG performance status of 0 or 1.

8. For Phase I part only : Female participant must be in postmenopausal status at the time of starting study treatment

9. For Phase II part only

   • Female participant is post-menopausal at the time of starting study treatment.

   • Female participant is pre/peri-menopausal at the time of starting study treatment

   
   

Key Exclusion Criteria

1. Symptomatic visceral disease or any disease burden that are at risk of life-threatening complications as per the investigator’s judgment.

2. Prior treatment with chemotherapy in the metastatic setting (allowed in neoadjuvant/ adjuvant setting, unless progression or recurrence occurred during or within 12 months after completion of adjuvant chemotherapy).

3. Prior treatment with capecitabine

4. Inflammatory breast cancer at screening.

5. Concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol

6. Hx of impaired cardiac function, clinically significant cardiac disease or ECG abnormalities

   Receiving brivudine which cannot be discontinued at least 4-week prior to start of capecitabine therapy.R

7. eceiving NEP inhibitors (i.e., Entresto®) and images for dosimetry assessments cannot be acquired for this participant

8. Known deficiency or family history of deficiency of dihydropyrimidine dehydrogenase.

   • For Phase II part only: Pregnant or breast-feeding women; Women of childbearing potential

Sponsor: Novartis

CRP Contact:  wagdy.rezk@ladydavis.ca

514-340-8222 ext. 25728

hend.al-bizri@ladydavis.ca

514-340-8222 ext. 23674

CRP PI: Dr. K. Ma

Status: Open to accrual