CTRI/2022/10/046630 [Registered on: 19/10/2022] Trial Registered Prospectively
Last Modified On:
08/08/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A Study of Dato-DXd Versus Investigators 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
Scientific Title of Study
A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator’s Choice of Chemotherapy in Patients who are not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast02)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
D926PC00001 Local Addendum version 1.0 Dated 09 Mar 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Senior Director, Oncology Country Head Site Management and Monitoring – India
Affiliation
AstraZeneca Pharma India Ltd.
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road
Bangalore KARNATAKA 560045 India
Phone
91-9845079472
Fax
Email
Sandeep.AV@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB 151 85 Sodertalje, Sweden
Primary Sponsor
Name
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore – 560045,
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca AB
151 85 Södertälje Sweden
Countries of Recruitment
Afghanistan Belgium Brazil Canada China France Germany Hungary India Italy Japan Mexico Philippines Poland Republic of Korea Russian Federation Singapore South Africa Spain Taiwan Thailand Turkey United Kingdom United States of America
Institutional Ethics Committee Mahatma Gandhi Medical College & Hospital
Submittted/Under Review
Institutional Ethics Committee, HCG Cancer Centre, Vizag
Approved
Institutional Ethics Committee, Kailash Cancer Hospital And Research Center
Approved
Institutional Ethics Committee, Sri Shankara Cancer Hospital and Research Centre, Bangalore
Approved
INSTITUTIONAL REVIEW BOARD ,TATA MEDICAL CENTER
Approved
Institutional Review Board Rajiv Gandhi Cancer Institute & Research Centre
Approved
Kingsway Hospitals Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Datopotamab deruxtecan
6.0 mg/kg IV on Day 1, Q3W
Comparator Agent
Investigator Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel, Capecitabine, Eribulin mesylate, Carboplatin)
Paclitaxel (80 mg/m2 IV on Day 1, Day 8 and Day 15, Q3W)
Nab-paclitaxel (100 mg/m2 IV Day 1, Day 8 and Day 15, every 4 weeks [Q4W])
Capecitabine (1000 or 1250 mg/m2 oral twice daily on Days 1 to 14, Q3W);choice between the 2 doses will be determined by standard institutional practice.
Eribulin mesylate (1.4 mg/m2 IV on Day 1 and Day 8, Q3W)
Carboplatin (area under the curve [AUC] 6 [using Calvert formula] IV Day 1, Q3W)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
90.00 Year(s)
Gender
Both
Details
Inclusion criteria:
1. Participant must be ≥ 18 years (≥ 20 years in Japan) at the time of screening.
2. Histologically or cytologically documented locally recurrent inoperable 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 targeted systemic 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:
1) relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer,
2) comorbidities precluding PD-1/PD-L1 inhibitor therapy, or
3) 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
7. Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), per investigator assessment.
8. Has had an adequate treatment washout period before Cycle 1 Day 1
9. Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation.
10. Participants with a history of previously treated neoplastic spinal cord compression or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they have recovered from acute toxic effects of radiotherapy.
11. Adequate organ and bone marrow function within 7 days before day of first dosing
. Haemoglobin ≥ 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
Absolute neutrophil count ≥ 1.5 × 109/L (granulocyte colony-stimulating factor administration is not allowed within 1 week prior to screening assessment).
Platelet count ≥ 100 × 109/L (platelet transfusion is not allowed within 1 week prior to screening assessment).
Total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN for AST/ALT (< 5 × ULN in participants with liver metastases).
Calculated CrCL ≥ 30 mL/minute as determined by Cockcroft-Gault (using actual body weight)
12. Minimum life expectancy of 12 weeks.
ExclusionCriteria
Details
Inclusion criteria:
1. Participant must be ≥ 18 years (≥ 20 years in Japan) at the time of screening.
2. Histologically or cytologically documented locally recurrent inoperable 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 targeted systemic 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:
1) relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer,
2) comorbidities precluding PD-1/PD-L1 inhibitor therapy, or
3) 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
7. Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), per investigator assessment.
8. Has had an adequate treatment washout period before Cycle 1 Day 1
9. Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation.
10. Participants with a history of previously treated neoplastic spinal cord compression or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they have recovered from acute toxic effects of radiotherapy.
11. Adequate organ and bone marrow function within 7 days before day of first dosing
. Haemoglobin ≥ 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
Absolute neutrophil count ≥ 1.5 × 109/L (granulocyte colony-stimulating factor administration is not allowed within 1 week prior to screening assessment).
Platelet count ≥ 100 × 109/L (platelet transfusion is not allowed within 1 week prior to screening assessment).
Total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN for AST/ALT (< 5 × ULN in participants with liver metastases).
Calculated CrCL ≥ 30 mL/minute as determined by Cockcroft-Gault (using actual body weight)
12. Minimum life expectancy of 12 weeks.
Exclusion criteria:
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) 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).
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 may be included (eg, hearing loss) after consultation with the sponsor study clinical lead or designee.
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; or is positive for hepatitis B or C virus, based on the evaluation of tests for hepatitis B (hepatitis B virus surface antigen, anti-hepatitis B virus surface antibody, and anti-hepatitis B virus core antibody, or hepatitis B virus DNA) or hepatitis C (hepatitis C antibody or hepatitis C virus ribonucleic acid [RNA]) infection at screening.
6. Known human immunodeficiency virus (HIV) infection that is not well controlled.
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. Investigator judgment of any one of the following:
Mean resting corrected QT interval corrected by Fridericia’s formula (QTcF) > 470 ms regardless of gender, obtained from triplicate 12-lead electrocardiograms (ECGs) performed at screening.
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. Clinically severe pulmonary function compromise resulting from intercurrent clinically significant pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of first dosing, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis, etc.) where there is documented or suspected pulmonary involvement at the time of screening.
12 Leptomeningeal carcinomatosis.
13 Clinically significant corneal disease.
14 Known active tuberculosis infection
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Radiological Progression-Free Survival (PFS) - time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first &
Overall Survival (OS)-time from randomization to death from any cause
For PFS, From Randomization Every 6 weeks (± 7 days) from randomisation for 48 weeks, then every 9 weeks (±7 days) thereafter until RECIST 1.1 disease progression.
For OS, every 3 months ± 14 days following objective PD or treatment discontinuation until the end of the study
Secondary Outcome
Outcome
TimePoints
Objective response rate (ORR)
Data obtained from randomisation up until progression (Every 6 weeks (± 7 days) from randomisation for 48 weeks, then every 9 weeks (±7 days) thereafter until RECIST 1.1 disease progression.)
Duration of response (DOR)
Every 6 weeks (± 7 days) from randomisation for 48 weeks, then every 9 weeks (±7 days) thereafter until RECIST 1.1 disease progression
Disease control rate (DCR)
At 12 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD, per RECIST 1.1 From randomisation up until progression.
Time to deterioration (TTD)
From Randomization to deterioration or End of study at each patient visit.
Time to second progression or death (PFS2)
Following objective progression that is confirmed by investigator assessment, participants will have their subsequent progression status recorded every 3 months (± 14 days) per local standard clinical practice to assess PFS2.
Time to Second Subsequent Therapy (TSST)
From randomisation to (each patient visit per protocol) until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.
Target Sample Size
Total Sample Size="600" Sample Size from India="23" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase III, randomised, open-label, 2-arm, multicentre,
international study assessing the efficacy and safety of Dato-DXd compared with
ICC in participants with locally recurrent inoperable or metastatic TNBC who
are not candidates for PD-1/PD-L1 inhibitor therapy.
The primary purpose of the study is to determine the efficacy and safety
of Dato -DXd compared with investigator’s choice single agent chemotherapy in
the target population.
Approximately 800 participants with TNBC will be screened/enrolled to
achieve
approximately 600 randomised to study intervention ({andomised 1:1 to
either Dato-DXd 6.0 mg/kg IV Q3W or ICC (Paclitaxel, Nab-paclitaxel,
Capecitabine, Eribulin mesylate, Carboplatin)} .
Randomisation will be stratified by the following prognostic factors:
Geographic region (Region 1 [US,
Canada, Europe] versus Region 2 [Rest of World])
DFI history (de novo versus prior
DFI ï‚£ 12 months versus prior DFI > 12 months)
PD-L1 status (positive [CPS ≥ 10]
versus negative [CPS < 10])
A recruitment cap of 20% of the randomised participants will be applied
to participants who have a DFI ≤ 12 months.
A recruitment cap of approximately 10% of the randomised participants
will be applied to participants who have PD-L1-positive (CPS ≥ 10) tumours who
would otherwise be eligible for pembrolizumab but do not have regulatory access
to pembrolizumab (participant’s country does not have regulatory approval at
the time of screening).
All participants will receive study intervention until
investigator-defined disease progression according to RECIST 1.1, or until
unacceptable toxicity, withdrawal of consent, or another criterion for
discontinuation is met. Intervention beyond RECIST 1.1-defined radiological progression
is not permitted in this study. No crossover between study treatment arms will
be allowed. Switching between ICC chemotherapy agents is not permitted.
Tumor evaluation scan will be performed at screening (as baseline)
followed by every 6 weeks (± 7 days) from randomisation for 48 weeks, then
every 9 weeks
(±7 days) thereafter until RECIST 1.1 disease progression (as assessed by
the
investigator), regardless of study intervention discontinuation or start
of subsequent anti-cancer therapy. Following disease progression, 1 additional
follow-up tumour imaging assessment should be performed per imaging schedule
(ie, either 6 weeks or 9 weeks later).
The study will compare PFS, OS and other measures of efficacy between the
study treatment groups and further characterize the safety and tolerability
profile of Dato DXt.
Duration of Treatment: Unless specific treatment discontinuation criteria
are met or the patient withdraws consent, all patients will continue receiving
treatment until disease progression. For patients randomized to the
investigator’s choice single agent chemotherapy arm, crossover to Dato-DXd will
not be permitted.
Follow-up of Participants Post-discontinuation of Study Intervention:
After study intervention discontinuation, all participants will undergo an
end-of-treatment visit (within 7 days of the decision to discontinue treatment)
and will be followed up for safety assessments 28 + 7 days after their last
dose of study intervention (ie, the safety follow-up visit).
Participants who have discontinued study intervention in the absence of
RECIST 1.1-defined radiological progression (by investigator assessment) will
be followed up with tumour assessments according to the SoA until RECIST
1.1-defined PD (as assessed by the investigator) or death regardless of whether
or not the participant started a subsequent anti-cancer therapy, unless they
have withdrawn all consent to study-related assessments.
In addition, all participants will be followed up for survival status
after intervention discontinuation every 3 months ± 14 days from the date of
the safety follow-up visit until death, withdrawal of consent, or the end of
the study (ie, progression/survival follow-up), per the SoA.
Participants may also be followed up for time to
second progression or death (PFS2) and subsequent anti-cancer therapy use after
intervention discontinuation every 3 months (± 14 days) from the date of the
safety follow-up visit until death, withdrawal of consent, or the end of the study (ie,
progression/survival follow-up), per the SoA.