Investigating Datopotamab Deruxtecan Plus Durvalumab Versus Datopotamab Deruxtecan in Patients With PDL1-negative Metastatic Triple-negative Breast Cancer

NCT06954480 | Recruiting Phase 2 DMC

• 1 other identifier: 1011098
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

The DIAMOND study is being carried out to evaluate if Datopotamab deruxtecan (Dato-DX) in combination with Durvalumab is more effective than Dato-DXd alone in treating PDL1-negative advanced or metastatic triple negative breast cancer (TNBC). Globally, breast cancer is the most common malignancy in women and the second most common cancer overall. The term TNBC is used to define tumours that do not express oestrogen receptors, progesterone receptors and HER2 receptors. TNBC comprises 10 -15% of all breast cancers. It remains the subtype with poorest outcome and there is a significant need to develop new therapies for this group of patients especially. Moreover, the PDL1-negative tumour has demonstrated no benefit from standard 1st line treatment of chemotherapy plus immune checkpoint inhibitors.

Conditions

Triple Negative Breast Cancer

Keywords

Triple Negative Breast Cancer; breast cancer; PDL1-negative; Datopotamab Deruxtecan; Durvalumab

Outcome Measures

Primary Outcomes (1)

• PFS is defined as the time from the date of randomisation to the date of first documented confirmed tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first in all patients.

  PFS is defined as the time from randomisation to disease progression or relapse (as assessed by the site radiologist and/or investigator, using RECIST, Version 1.1) or death on study from any cause (defined as death within 30 days of the last study treatment), whichever occurs first. For patients who have not died or experienced disease progression at the end of study, PFS will be censored on the last date the patient was known to be progression free.

  PFS is defined as the time from the date of randomisation to date of first documented confirmed disease progression or death, which ever occurs first, assessed on average up to 12 months.

Secondary Outcomes (6)

• OS is defined as the time from date of randomisation to the date of death due to any cause in all patients.

  From date of randomisation to the date of death due to any cause in all patients, assessed on average up to 12 months.

• DoR is defined as the time from first documentation of CR or PR to confirmed disease progression using RECIST 1.1, or death on study from any cause, whichever occurs first, in patients with objective response.

  The time from first documentation of CR or PR to confirmed disease progression, or death on study from any cause, whichever occurs first in patients with objective response, assessed on average up to 12 months.

• CBR is defined as the percentage of patients who have achieved at least one CR or PR or met the SD criteria at least once after randomisation for a minimum interval of 24 weeks continuously (using RECIST 1.1).

  Up to 24 weeks

• DoCB is calculated as time (in months) from randomisation to progression or death from any cause in patients with a clinical benefit.

  From the time (in months) from randomisation to progression or death from any cause in patients with a clinical benefit, assessed on average up to 12 months..

• Changes in quality of life measured by the time to deterioration (TTD)

  From the time of enrollment to the safety visit (90 days +/- 7 days after the last dose.), assessed up to at least 122 PFS events have occured

Study Arms (2)

Dato-DXd plus Durva

EXPERIMENTAL

In arm A, patients will receive Durvalumab 1120mg plus Dato-DXd 6.0mg/kg.

Drug: Datopotamab Deruxtecan (Dato-DXd); Drug: Durvalumab

Arm B - Dato-DXd

ACTIVE COMPARATOR

In arm B, patients will receive Dato-DXd 6.0mg/kg.

Drug: Datopotamab Deruxtecan (Dato-DXd)

Interventions

Datopotamab Deruxtecan (Dato-DXd) DRUG

Patients will receive Dato-DXd 6.0mg/kg, which will be administered by infusion on day 1 of each 21-day cycle.

Arm B - Dato-DXd; Dato-DXd plus Durva

Durvalumab DRUG

Patients will receive Durva 1120mg, which will be administered by infusion on day 1 of each 21-day cycle.

Dato-DXd plus Durva

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Ability to comply with the protocol.
• Female ≥ 18 years of age.
• Triple-negative disease, defined as tumour cells being:
• Negative for ER with \<10% of tumour cells positive for ER on IHC or IHC score (Allred) of ≤3.
• Negative for PR with \<10% of tumour cells positive for PR on IHC or IHC score (Allred) of ≤3 or PR unknown, and
• Negative for HER2 with 0, 1+ or 2+ intensity on IHC and no evidence of amplification on ISH.
• PDL1 negative, defined as 22C3 CPS\<10.
• Patients must have:
• at least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computed tomography (CT) or magnetic resonance imaging (MRI) performed within 28 days prior to randomisation which is suitable for accurate repeated measurements, or
• lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable disease as defined above; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible. Patient that cannot be assessed by the CT or MRI should be excluded from the study.
• Representative formalin-fixed paraffin embedded (FFPE) breast tumour samples with an associated pathology report from the primary or recurrent cancer that are determined to be available and sufficient for central testing OR tumour accessible for biopsy.
• ECOG performance status 0-1.
• Life expectancy ≥12 weeks.
• Adequate haematologic and end-organ function within 28 days prior to the first study treatment defined by the following:

You may not qualify if:

• Prior chemotherapy, immunotherapy (including durvalumab) or treatment with PARP inhibitors for advanced or metastatic breast cancer.
• Prior treatment with immune checkpoint inhibitors (eg atezolizumab, pembrolizumab) or DNA topoisomerase I or TROP2- or HER2-targeting ADCs and TROP2 targeted therapy in the (neo)adjuvant setting within 6 months from the end of treatment and randomisation into this study.
• Patients with prior allogeneic stem cell or solid organ transplantation.
• Patients must not have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent), or had oral or IV steroids for 14 days prior to the first dose of study drug; the use of intranasal, inhaled corticosteroids topical steroids, or local steroid injections, physiologic replacement doses of glucocorticoids (i.e. for adrenal insufficiency) and mineralocorticoids (e.g. fludrocortisone) or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication is allowed.
• Administration of a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Active or prior documented autoimmune or inflammatory disorders including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, , rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis , Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included
• Patients with celiac disease controlled by diet alone
• History of idiopathic pulmonary fibrosis (including pneumonitis or interstitial lung disease), drug-induced pneumonitis, radiation pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) requiring steroids, or evidence of active pneumonitis on screening chest CT scan.
• Active infection requiring systemic therapy.
• History of HIV infection.
• Known active hepatitis infection (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

Sponsors & Collaborators

• Queen Mary University of London: lead
• AstraZeneca: collaborator

Study Sites (2)

Barts Cancer Institute, Centre of Experimental Cancer Medicine

London, EC1M 6BQ, United Kingdom

NOT YET RECRUITING

Barts Health NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Peter Schmid, MD PhD, FRCP

  Queen Mary University of London

  STUDY DIRECTOR

Central Study Contacts

Peter Schmid, MD PhD, FRCP

CONTACT

+44(0)20 7882 8764; bci-diamond@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: May 1, 2025
• Study Start: October 27, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: November 19, 2025

Record last verified: 2025-04

Locations

GB (2)