A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy
- Conditions
- Breast Cancer
- Registration Number
- JPRN-jRCT2061220029
- Lead Sponsor
- Inoguchi Akihiro
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 600
Age
1. Participant must be >= 18 years at the time of screening.
Type of Participant and Disease Characteristics
2. Histologically or cytologically documented locally recurrent inoperable TNBC, which cannot be treated with curative intent, or metastatic TNBC. TNBC is defined as:
- Negative for ER with < 1% of tumour cells positive for ER on IHC.
- Negative for progesterone receptor with < 1% of tumour cells positive for progesterone receptor on IHC.
- Negative for HER2 with 0 or 1+ intensity on IHC or 2+ intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guideline.
3. No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
4. Not a candidate for PD-1/PD-L1 inhibitor therapy, defined as:
- Participants whose tumours are PD-L1-negative, or
- Participants whose tumours are PD-L1-positive and have:
a. relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer,
b. comorbidities precluding PD-1/PD-L1 inhibitor therapy, or
c. no regulatory access to pembrolizumab [participant's country does not have regulatory approval at the time of screening]).
5. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and is suitable for accurate repeated measurements.
6. ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
7. Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), based on DFI and prior taxane exposure, per investigator assessment.
8. Has had an adequate treatment washout period before Cycle 1 Day 1, defined as:
- Major surgery: >= 3 weeks.
- Radiation therapy including palliative radiation to chest: >= 4 weeks (palliative radiation therapy to other areas >= 2 weeks).
- Corticosteroid therapy for central nervous system metastatic disease: > 3 days.
- Anti cancer therapy including hormonal therapy: >= 3 weeks (for small molecule targeted agents: >= 2 weeks or 5 half-lives, whichever is longer).
- Nitrosoureas or mitomycin C: >= 6 weeks.
- Antibody-based anti cancer therapy: >= 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases).
- Immunotherapy (non-antibody-based therapy), retinoid therapy: >= 2 weeks or 5 times the terminal elimination half-life of the agent, whichever is longer.
- Chloroquine/hydroxychloroquine: > 14 days.
9. Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation. All participants must have a FFPE metastatic (excluding bone) or locally recurrent inoperable tumour sample (block preferred, or a minimum of 20 freshly cut slides) available, collected <= 3 months prior to screening. If neither an adequate FFPE block nor the minimum of 20 slides are available from the most recent biopsy, or if a biopsy is not feasible for safety reasons, and this is clearly documented, an archival tumour specimen obtained before the diagnosis of locally recurrent inoperable or metastatic breast cancer may be submitted, pending approval by the Global Study Team.
10. Participants
Medical Conditions
1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, or significant cardiac or psychological conditions), and/or substance abuse which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence (per investigator assessment). Exceptions include adequately resected non-melanoma skin cancer (basal cell carcinoma of the skin or squamous cell carcinoma of the skin) and curatively treated in situ disease.
3. Persistent toxicities caused by previous anti-cancer therapy, excluding alopecia, not yet improved to Grade <= 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss).
4. Uncontrolled infection requiring IV antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
5. Known active or uncontrolled hepatitis B or C virus infection.
6. Known human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, cluster of differentiation (CD)4+ count > 350 cells/mm3, no history of an acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications.
7. Uncontrolled or significant cardiac disease including:
- Myocardial infarction or uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1
- Congestive heart failure (New York Heart Association Class II to IV), or
- Uncontrolled or significant cardiac arrhythmia, or
- Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg).
8. Resting ECG with clinically abnormal findings.
9. Uncontrolled hypercalcaemia: > 1.5 mmol/L (> 6 mg/dL) ionised calcium, or serum calcium (uncorrected for albumin) > 3 mmol/L (> 12 mg/dL), or corrected serum calcium > ULN, or clinically significant (symptomatic) hypercalcaemia.
10. History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
11. Has severe pulmonary function compromise.
12. Leptomeningeal carcinomatosis.
13. Clinically significant corneal disease.
14. Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
Prior/Concomitant Therapy
15. Prior exposure to:
- Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I
- TROP2-targeted therapy
- Prior treatment with same ICC agent
- Chloroquine/hydroxychloroquine without an adequate treatment washout period of > 14 days prior to randomisation.
16. Any concurren
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method