Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Gemcitabine

Capecitabine

Vinorelbine

Hormones

Immunoglobulins

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Arm 2: ICC

Capecitabine

Gemcitabine

Eribulin mesylate

Vinorelbine

Experimental drug. Provided in 100mg vials. IV infusion.

Dato-DXd

Tablet. Oral route of administration. Active comparator

Eribulin

The study will evaluate the safety and efficacy of datopotamab deruxtecan (also known as Dato-DXd, DS-1062a), when compared with Investigator's choice of standard of care single-agent chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine) in participants with inoperable or metastatic HR-positive, HER2- negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy.

The primary objective of this study will assess the safety and efficacy of datopotamab deruxtecan (Dato-DXd) in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy.

The study will be stratified based on number of previous lines of chemotherapy (1 vs. 2), prior use of CDK4/6 inhibitors (Yes vs. no) and geographic region of participant (US/Canada/Europe vs. rest of world).

This study aims to see if datopotamab deruxtecan allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.

A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by BICR, or death due to any cause. The analysis will include all randomized participants as randomized regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1. The measure of interest is the hazard ratio of PFS.

OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the hazard ratio of OS.

Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as determined by the BICR/Investigator assessment, per RECIST 1.1.

Duration of response is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/Investigator assessment or death due to any cause.

PFS by Investigator assessment will be defined as the time from the date of randomization until the date of PD per RECIST 1.1 (by Investigator assessment) or death (by any cause in the absence of progression), (ie, date of event or censoring - date of randomization + 1).

Disease control rate 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, as assessed BICR/per investigator assessment and derived from the raw tumor data for at least 11 weeks after randomization.

Time to first subsequent therapy is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.

Time to second subsequent therapy is defined as the time from randomization to until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.

Time to second progression of death will be defined as the time from the randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice.

The secondary PRO endpoints include: TTD in pain as measured by the pain scale from EORTC QLQ-C30

Plasma concentrations of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a (payload).

To test for the presence of ADA to investigate the immunogenicity of Dato-DXd.

The secondary PRO endpoints include: TTD in physical functioning as measured by the physical functioning scale from EORTC QLQ-C30

The secondary PRO endpoints include: TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC QLQ-C30

Daiichi Sankyo

AstraZeneca

Triple Negative Breast Neoplasms

Pembrolizumab

Durvalumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles

Arm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles

Arm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles

Pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles

Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles

\* Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3.

Experimental drug. Provided in 100mg vials. IV infusion

Experimental drug. Provided in 50mg vials. IV infusion

Active Comparator. Tablet. Oral route of administration

Active Comparator. Provided in 100mg vials. IV infusion

AstraZeneca Clinical Study Information Center

Aditya Bardia, MD, MPH

This is a Phase III, randomized, open-label, 3-arm, multicenter, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with ICT in participants with stage I to III TNBC with residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.

The study will investigate the efficacy and safety of Dato-DXd with or without durvalumab when compared with ICT (capecitabine and/or pembrolizumab) in participants with stage I to III TNBC who have residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.

The primary objective of the study is to demonstrate superiority of Dato-DXd in combination with durvalumab relative to ICT by assessment of iDFS in participants with stage I to III TNBC with residual invasive disease at surgical resection following neoadjuvant therapy.

A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)

A Phase 3 Open-label, Randomised Study of Datopotamab Deruxtecan (DatoDXd) With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Who Have Residual Invasive Disease in the Breast and/or Axillary Lymph Nodes at Surgical Resection Following Neoadjuvant Systemic Therapy (TROPION-Breast03)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause.

iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs ICT.

DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause.

DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments.

The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd + durvalumab vs ICT.

DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd vs ICT.

DDFS is defined as time from randomisation to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment based on all available clinical assessments. The measure of interest will be the HR (hazard ratio) of DDFS for Dato-DXd + durvalumab vs Dato-DXd.

OS is defined as time from randomisation until date of death due to any cause.

The analysis will include all randomised participants, as randomised regardless of whether the participant withdraws from randomised therapy or received another anticancer therapy. The measure of interest will be the HR (hazard ratio) of OS for Dato-DXd + durvalumab vs ICT.

OS is defined as time from randomisation until date of death due to any cause. The measure of interest will be the HR (hazard ratio) of OS for Dato-DXd vs ICT.

iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause.

iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd vs ICT.

iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs Dato-DXd.

Time to Deterioration (TTD) and actual scores in physical function as measured by the PROMIS Physical Function Short Form 8c.TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold.

The analysis will include all dosed participants. The measure of interest is the HR (hazard ratio) of TTD and mean between-arm difference in physical function for Dato-DXd with or without durvalumab compared with ICT.

Time to Deterioration (TTD) and actual scores in GHS/QoL as measured by the GHS/QoL scale from the EORTC IL172.

TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold.

The analysis will include all randomised participants. The measure of interest is the HR (hazard ratio) of TTD and mean between-arm difference in GHS/QoL for Dato-DXd with or without durvalumab compared with ICT.

Proportion of participants experiencing different levels of fatigue at 3 months (13weeks), 6 months (26 weeks), and 12 months (52 weeks) as measured by PROMIS Fatigue Short Form 7a.

The analysis will include all dosed participants. The measure of interest will be the proportion of participants reporting different levels of fatigue.

Concentration of Dato- DXd, total anti-TROP2 antibody, and MAAA-1181 in plasma.

Presence of ADAs for Dato-DXd (confirmatory results: positive or negative; titres).

Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE version 5.0).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)	NCT05104866	Breast Cancer	Dato-DXd Capecitabine Gemcitabine Eribulin Vinorelbine	18 Years -	AstraZeneca
A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)	NCT05629585	Breast Cancer	Dato-DXd Durvalumab Capecitabine Pembrolizumab	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for ds1062a

Every month we try and update this database with for ds1062a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ds1062a

Every month we try and update this database with for ds1062a cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ds1062a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.