DYNASTY - Breast02 (JCP153)

A Phase 3, Randomized, Multi-center, Open-label Study of DB-1303 Versus Investigator’s Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02)

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Population: HR+, HER2-low metastatic Breast Cancer

Line of therapy: 2L - After Progression on Previous Endocrine Therapy

Intervention: DB-1303 Versus Investigator’s Choice Chemotherapy

Key Inclusion Criteria

1. Advanced or metastatic 2) Has HER2-low expression (IHC 1+ or IHC 2+/ISH-) as determined by the central laboratory result.

2. Was never previously reported as HER2-positive (IHC 3+ or ISH+) as per ASCO/CAP guidelines.

3. Is documented as HR+ (either estrogen receptor [ER] and/or progesterone receptor [PgR] positive [ER or PgR ≥1%]) per ASCO/CAP guidelines.

4. Must have an adequate tumor tissue sample available for assessment of HER2 by central laboratory, preferably in formalin fixation and paraffin embedding blocks based on a mandatory FFPE tumor sample obtained at the time of metastatic disease or later;

5. ECOG of 0 or 1.

6. Must have had either: Disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator, OR Disease progression on at least 2 previous lines of ET with or without a targeted therapy (such as CDK4/6, mammalian target of rapamycin [mTOR] or phosphoinositide 3-kinase [PI3-K] inhibitors) administered for the treatment of metastatic disease.

7. No prior chemotherapy for advanced or metastatic breast cancer. Subjects who have received chemotherapy in the neo-adjuvant or adjuvant setting are eligible, as long as they have had a disease-free interval (defined as completion of systemic chemotherapy to diagnosis of advanced or metastatic disease) of >12 months.

8. Subjects must have at least one measurable lesion as defined per RECIST v1.1 or have non-measurable, bone-only disease that can be assessed by computer tomography (CT) or Magnetic Resonance Imaging (MRI) or X-Ray.

   
   

Key Exclusion Criteria

1. Ineligible for all options in the investigator's choice chemotherapy arm.

2. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events or compromise the ability of the subject to give written informed consent.

3. Clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to the randomization.

4. Uncontrolled or significant cardiovascular disease

5. Has as a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

6. Subjects with prior use of immunosuppressive medication within 14 days prior to first study dose, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses less than 10 mg/day of prednisone or equivalent.

7. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.

8. Previous treatment with anti-HER2 therapy.

9. Prior treatment with antibody-drug conjugate that comprised an exatecan derivative that is a topoisomerase I inhibitor.

Sponsor: Duality Bio Inc.

CRP Contact:  wagdy.rezk@ladydavis.ca

514-340-8222 ext. 25728

CRP PI: Dr. C. Ferrario

Status: Open to accrual