A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer

PHASE3RECRUITING

This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer.

info
Simpliy with AI

Study details:

The primary objectives of the study are to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor low/HER2-negative breast cancer, by central assessment of pCR and/or to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer, by investigator assessment of EFS.

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Participant must be ≥ 18 years, at the time of signing the ICF.
  • Histologically confirmed Stage II or III unilateral or bilateral primary invasive TNBC or hormone receptor-low/HER2-negative breast cancer
  • ECOG PS of 0 or 1
  • Provision of acceptable tumor sample
  • Adequate bone marrow reserve and organ function
  • Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Exclusion criteria

  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before randomization and of low potential risk for recurrence.
  • Evidence of distant disease.
  • Clinically significant corneal disease.
  • Has active or uncontrolled hepatitis B or C virus infection.
  • Known HIV infection that is not well controlled.
  • Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections; or inability to rule out infections.
  • Known to have active tuberculosis infection
  • Resting ECG with clinically significant abnormal findings.
  • Uncontrolled or significant cardiac disease.
  • History of non-infectious ILD/pneumonitis
  • Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for TNBC or hormone receptor-low/HER2-negative breast cancer
  • For females only: is pregnant (confirmed with positive serum pregnancy test) or breastfeeding, or planning to become pregnant.
  • Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of study intervention, or as dictated by local PI for SoC if longer.
  • info
    Simplify with AI

    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2023-11-14

    Primary completion: 2028-03-29

    Study completion finish: 2030-08-28

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE3

    trial

    Trial ID

    NCT06112379

    Intervention or treatment

    DRUG: Dato-DXd

    DRUG: Durvalumab

    DRUG: Pembrolizumab

    DRUG: Doxorubicin

    DRUG: Epirubicin

    DRUG: Cyclophosphamide

    DRUG: Paclitaxel

    DRUG: Carboplatin

    DRUG: Capecitabine

    DRUG: Olaparib

    Conditions

    • Breast Cancer

    Find a site

    Closest Location:

    Research Site

    Research sites nearby

    Select from list below to view details:

    • Research Site

      Darlinghurst, Not Specified, Australia

    • Research Site

      East Melbourne, Not Specified, Australia

    • Research Site

      Heidelberg, Not Specified, Australia

    • Research Site

      Herston, Not Specified, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Dato-DXd plus durvalumab
    • Participants receive durvalumab every 3 weeks (Q3W) + Dato-DXd Q3W as neoadjuvant therapy prior to surgery; followed by 9 cycles of durvaluamb Q3W as adjuvant therapy post-surgery. Adjuvant chemotherapy may be given in combination with durvalumab only if participants have residual disease.
    • Olaparib may be given for participants with gBRCA-positive tumours and residual disease
    • Adjuvant chemotherapy may be one of these:
    • 1. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) and carboplatin (weekly or Q3W) for 4 cycles (12 weeks);
    • 2. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks);
    • 3. Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks);
    • 4. Capecitabine (Q3W) for 8 cycles.
    DRUG: Dato-DXd
    • Experimental drug IV infusion
    ACTIVE_COMPARATOR: Pembrolizumab plus chemotherapy
    • Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Adjuvant capecitabine (Q3W) for 8 cycles may be given in combination with pembrolizumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease.
    DRUG: Pembrolizumab
    • IV Infusion Active comparator

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Pathologic Complete Response (pCR) in the experimental vs control armspCR rate is defined as the proportion of participants who have no evidence by haematoxylin and eosin staining of residual invasive disease at the time of definitive surgery in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by blinded central evaluation. 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 difference between the pCR rates.At the time of definitive surgery
    Event-free survival (EFS) in the experimental vs control armsEFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: disease progression precluding surgery, disease recurrence (local, regional, distant, or contralateral), second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death by any cause (in the absence of recurrence). 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 Hazard Ratio of EFS.Date of randomization to date of the EFS event, up to 68 months after the first subject randomized

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Overall Survival (OS) in the experimental vs control armsOS is defined as the time from the date of randomisation until the 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 receives another anticancer therapy. The measure of interest will be the Hazard Ratio of OS.Date of randomization to date of death due to any cause, up to 82 months after the first subject randomized
    Distant disease-free survival (DDFS) in the experimental vs control armsDDFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: distant metastasis, occurrence of second primary non-breast invasive cancer (other than squamous or basal cell skin cancer), or death by any cause (in the absence of recurrence). 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 Hazard Ratio of DDFS.Date of randomization to date of the DDFS event, up to 68 months after the first subject randomized
    Participant-reported breast and arm symptoms in the experimental vs. control armsBreast and arm symptoms measured by the EORTC IL116. 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 is the mean between-arm difference in breast and arm symptom scores.From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first.
    Participant-reported physical function in the experimental vs. control armsPhysical function measured by the PROMIS Physical Function Short Form 8c. The analysis will include all dosed participants. The measure of interest is the mean between-arm difference in physical function scores.From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
    Participant-reported fatigue in the experimental vs. control armsFatigue measured by the PROMIS Fatigue Short Form 7a. The analysis will include all dosed participants. The measure of interest will be the difference on the proportions of participants reporting different levels of fatigue and mean between-arm difference in the fatigue scores.From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
    Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control armsGlobal health status/Quality of life measured by EORTC IL172. 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 is the mean between-arm difference in GHS/QoL scores.From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).
    Pharmacokinetics of Dato-DXd (in combination with durvalumab)Plasma concentrations of Dato-DXd (ug/ml )Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
    Pharmacokinetics of Dato-DXd (in combination with durvalumab)Plasma concentrations of total anti-TROP2 antibody (ug/ml )Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
    Pharmacokinetics of Dato-DXd (in combination with durvalumab)Plasma concentrations of DXd (MAAA-1181a) (ng/ml)Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
    Immunogenicity of Dato-DXd (in combination with durvalumab)Presence of antidrug antibodies (ADAs) for Dato-DXd (confirmatory results: positive or negative, titres).Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit
    Safety of Dato-DXd (in combination with durvalumab)Safety and tolerability will be evaluated in terms of AEs graded by CTCAE version 5.0Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

    Clinical Trials Gov: A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer

    Other trails to consider

    Top searched conditions