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

Recruiting now · Phase 2

Conditions studied: Triple Negative Breast Cancer

In brief

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.

Key facts

Study ID

NCT06954480

Run by

Queen Mary University of London

People needed

140

Starts

2025-10-27

Expected to finish

2030-02-01

Last updated by the study team

2026-05-22

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

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:
• Absolute neutrophil count ≥ 1500 cells/μL (1.5 x 109/L) (without granulocyte) colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1).
• WBC > 2500/μL (2.5 x 109/L).
• Platelet count ≥ 100,000/μL (100 x 109/L) (transfusion not permitted within 28 days of study medication).
• Haemoglobin ≥ 9.0 g/dL (90g/L) with no blood transfusions (packed red blood cells).
• Serum albumin ≥ 3g/dL.
• AST (SGOT) or ALT (SGPT) and ALP ≤ 2.5 times the institutional upper limit of normal (ULN), bilirubin ≤ 1.5 x ULN (patients with liver metastases who have AST or ALT ≤ 5 x the institutional ULN may be enrolled).
• aPTT ≤ 1.5 × the institutional ULN, INR <1.5 and absence of evidence of impaired hepatic synthesis function. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
• Serum Creatinine ≤ 1.5 x institutional ULN.
• Glomerular filtration rate ≥ 40mL/min as assessed by standard methodology at the investigating center (i.e., Cockcroft Gault, MDRD or CKD-EPI formulae, EDTA clearance or 24 h urine collection).
• No evidence of haematuria: +++ on microscopy or dipstick.

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.
• Known history of active tuberculosis (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol.
• Concurrent treatment with other experimental drugs or participation in another clinical trial with therapeutic intent within 28 days prior to randomisation.
• Pregnant and lactating female patients.
• Major surgical procedure within 4 weeks prior to randomisation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
• Malignancies other than breast cancer within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent).
• Severe infections within 28 days prior to randomisation in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.

Where it is running

• Barts Health NHS Trust — London, United Kingdom (enrolling)
• Barts Cancer Institute, Centre of Experimental Cancer Medicine — London, United Kingdom

Full record on ClinicalTrials.gov

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