Study of Dato-DXd With or Without Durvalumab Compared With Investigators Choice of Chemotherapy in Combination With Pembrolizumab as first line therapy for Locally Recurrent Inoperable or Metastatic Breast Cancer
- Conditions
- Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
- Registration Number
- CTRI/2024/04/065629
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Inclusion Criteria
Age
1 Participant must be 18 years at the time of signing the informed consent form ICF.
Type of Participant and Disease Characteristics
2 Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC. TNBC is defined as:
Negative for ER with 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 guidelines
3 ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.
4 All participants must provide a FFPE metastatic excluding bone or locally recurrent inoperable tumour sample collected 3 months prior to signing of informed consent ie, start of screening..
5 PD L1 positive TNBC based on results from an appropriately validated investigational PD L1 22C3 assay CPS 10 from a sponsor-designated central laboratory.
6 No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
7 Eligible for one of the chemotherapy options listed as ICC paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin
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 CNS metastatic disease: 3 days.
Anticancer therapy including hormonal therapy: 3 weeks for small molecule targeted agents: 2 weeks or 5 half-lives, whichever is longer.
Chloroquine/hydroxychloroquine: 14 days.
9 Measurable disease by computed tomography CT or MRI as per RECIST 1.1.
10 Adequate bone marrow reserve and organ function within 7 days before Cycle 1 Day 1 as follows
11 Minimum life expectancy of 12 weeks.
Sex and Contraceptive/Barrier Requirements
12 Male or female.
Reproduction
Contraceptive use by females or males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria
Medical Conditions
1 As judged by the investigator, any evidence of diseases 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 with exceptions as defined in protocol
3 Persistent toxicities caused by previous anticancer therapy
4 Neoplastic spinal cord compression or active brain metastases
5 Has significant third-space fluid retention and is not amenable for required repeated drainage.
6 Uncontrolled infection requiring IV antibiotics, antivirals or antifungals; suspected infections ; or inability to rule out infections
7 Has active or uncontrolled hepatitis B or C virus infection.
8 Known HIV infection that is not well controlled.
9 Uncontrolled or significant cardiac disease
10 Participant meets one or more of the following, as judged by the investigator:
Mean resting corrected QT interval corrected by Fridericia’s formula QTcF 470 ms regardless of gender, obtained from a single 12-lead electrocardiogram ECG performed at screening.
History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and/or cause Torsades de Pointes.
Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
11 Uncontrolled hypercalcaemia
12 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.
13 Has severe pulmonary function compromise.
14 Leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis.
15 Clinically significant corneal disease.
16 Active or prior documented autoimmune or inflammatory disorders
Prior Concomitant Therapy
17 Prior exposure to:
a - Any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I.
b - TROP2-targeted therapy.
c - Chloroquine/hydroxychloroquine without an adequate treatment washout period of 14 days prior to randomisation.
18 Any concurrent anticancer treatment.
19 Concurrent use of systemic hormone replacement therapy (HRT eg, oestrogen and or progesterone or hormonal contraception. However, concurrent use of hormones for other non cancer related conditions eg, insulin for diabetes is acceptable.
20 Current or prior use of immunosuppressive medication within 14 days prior to randomisation.
21 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention
22 Major surgical procedure or significant traumatic injury 3 weeks of Cycle 1 Day 1 or an anticipated need for major surgery during the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2 <br/ ><br> <br/ ><br>PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. <br/ ><br>The comparison will include all randomised participants, as randomized. <br/ ><br>Timepoint: The primary (and final) PFS analysis for superiority will be performed after approximately 336 BICR PFS events have occurred across the Dato-DXd + durvalumab and ICC + pembrolizumab treatment groups (61% maturity).
- Secondary Outcome Measures
Name Time Method