Locally advanced, unresectable or metastatic solid malignancies Cancer
Conditions
Interventions
Current interventions:
The ATTAINMENT study is comprised of two modules: Module 1 and Module 2.
Module 1 includes dose escalation and dose expansion cohorts. In the dose escalation phase using a Bayes
Sponsors
Medannex Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 23/06/2025: Core: 1. Provision of signed written informed consent 2. Age 18 years old and over 3. ECOG Performance status 0-1 4. Adequate bone marrow function as defined by: 4.1. Absolute neutrophil count (ANC) =1.5×10^9/l 4.2. Platelet count =100×10^9/l 4.3. Haemoglobin level =9.0 g/dl 5. Adequate liver function, as defined by: 5.1. Serum total bilirubin =1.5×upper limit of normal (ULN) 5.2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5×ULN 6. Adequate renal function assessed as estimated glomerular filtration rate (eGFR) =50 ml/min/1.73m2 7. Ability to comply with protocol requirements 8. Female participants of child-bearing potential must have a negative serum pregnancy test Module 1: Participants being enrolled in Module 1 must meet all criteria listed below in addition to the Core Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of a solid tumour believed to overexpress ANXA1 (e.g., cholangiocarcinoma, triple negative breast, bladder, ovarian, colorectal, kidney, liver, pancreatic, gastric, prostate and lung) which is not amenable to standard therapy, is refractory to standard therapy or for which no standard therapy exists. Tumours identified as not responding to ANXA1 inhibition (i.e. head and neck (oral, nasal and throat regions) and cervical) are excluded. 2. Participants must have measurable disease per RECIST version 1.1 criteria and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions which do not fulfil RECIST version 1.1 criteria for measurable disease). Module 2: Participants being enrolled in Module 2 must meet the applicable inclusion criteria listed below in addition to the Core Inclusion Criteria: Arm 1: 1. Participants with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic pancreatic cancer. 2. Participants must be suitable for combination treatment. 3. Participants must have at least one measurable lesion as per RECIST version 1.1. Arm 2: 1. Participants with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic cholangiocarcinoma or gallbladder cancer. 2. Participants must have received and have documented evidence of progression following treatment with cisplatin and gemcitabine (with or without durvalumab). 3. Adequate biliary drainage, with no evidence of ongoing infection. 4. Participants must have at least one measurable lesion as per RECIST version 1.1. Previous inclusion criteria as of 28/06/2024: Core: 1. Provision of signed written informed consent 2. Age 18 years old and over 3. ECOG Performance status 0-1 4. Adequate bone marrow function as defined by: 4.1. Absolute neutrophil count (ANC) =1.5×10^9/l 4.2. Platelet count =100×10^9/l 4.3. Haemoglobin level =10.0 g/dl 5. Adequate liver function, as defined by: 5.1. Serum total bilirubin =1.5×upper limit of normal (ULN) 5.2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5×ULN 6. Adequate renal function assessed as estimated glomerular filtration rate (eGFR) =50 ml/min/1.73m2 7. Ability to comply with protocol requirements 8. Female participants of child-bearing potential must have a negative serum pregnancy test Module 1: Participants being enrolled in Module 1 must meet all criteria listed below in addition to the Core Inclusion Criteria: 1. Histologically or cytologically confirmed diagnos
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 23/06/2025: Core 1. Symptomatic central nervous system (CNS) or leptomeningeal metastases. 2. Residual toxicities from chemotherapy or radiotherapy, which have not regressed to Grade =1 severity (NCI CTCAE v5), except for neuropathy (Grade 2 allowed) or alopecia. 3. Participants receiving daily high-dose steroids (defined as >2 mg/day of dexamethasone or >15 mg/ day prednisolone) during the 14 days prior to the first dose of IMP. Participants who are receiving glucocorticoids as part of steroid replacement (e.g., after immunotherapy hypophysitis) remain eligible. 4. Participants who have a history of another malignancy diagnosed within the past 2 years, with the exception of adequately treated non-melanoma skin cancer, curatively treated carcinoma in situ of the cervix or ductal carcinoma in situ (DCIS) of the breast. Participants with previous invasive cancers are eligible if treatment was completed more than a year prior to initiating the trial, and the participant has had no evidence of recurrence since then. 5. Presence of an uncontrolled concomitant illness or active infection requiring intravenous (IV) antibiotics or a fever >38.5°C on the day of scheduled dosing. 6. Presence of any serious illnesses, medical conditions, or other medical history, including laboratory results, which, in the Investigator’s opinion, would be likely to interfere with their participation in the trial, or with the interpretation of the results. 7. Known diagnosis of human immunodeficiency virus (HIV) or active hepatitis B or C. Participants who are HBV carriers and receiving anti-viral prophylaxis are excluded. 8. Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location etc.) that, in the judgment of the Investigator, may affect the participant’s ability to sign the informed consent and undergo trial procedures. 9. Known allergy to any of the excipients of the MDX-124 drug product (histidine, sucrose and polysorbate 20). 10. Currently pregnant, lactating or breastfeeding. 11. All men or women of reproductive potential, unless using at least two highly effective contraceptive measures, or abstaining from sexual intercourse, until six months after the last dose of IMP. 12. History or presence of alcoholism or drug abuse within the past 2 years. 13. Participants who have received a live vaccine 4 weeks or fewer prior to enrolment. 14. Drugs that have anti-cancer characteristics or other compounds such as herbal, “alternative” or traditional Chinese medicine, which may have anti-cancer properties. Module 1: In addition to the core exclusion criteria, if participants being considered for enrolment in Module 1 meet any criteria listed below, they will be ineligible for the trial: 1. Prior chemotherapy, radiotherapy (other than a short cycle of palliative radiotherapy for bone pain) or other targeted therapy administered within 28 days of first receipt of IMP. - For immunotherapy, within 42 days of the first administration of IMP. - For targeted hormone therapy within 14 days of the first administration of IMP. Patients on standard-of-care hormonal therapies may continue that therapy. - For nitrosoureas and mitomycin C therapy within 42 days of the first administration of IMP. Module 2: In addition to the core exclusion criteria, if participants being considered for enrolment in Module 2 meet any criteria listed below, they will be ineligible for the trial: Arm 1: 1. Patient h
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measure as of 23/06/2025: 1. Treatment-emergent adverse events (per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5) recorded by the Investigator and trial site staff at the following study visits: 1.1. Module 1 dose escalation: screening, cycle 1 day 1, cycle 1 day 8, cycle 2 day 1, cycle 2 day 8, cycle 3 (and any subsequent cycles) day 1 onwards, end of treatment, and the 28-day follow-up visit (+/- 7 days) 1.2. Module 1 dose expansion: screening, cycle 1 day 1, cycle 1 day 8, cycle 1 day 15, cycle 2 (and subsequent cycles) day 1 onwards, end of treatment, and the 28-day follow-up visit (+/- 7 days) 1.3. Module 2 Arm 1: screening, cycle 1 (and subsequent cycles) day 1, day 8, day 15, day 22, end of treatment, and the 28-day follow-up visit (+/- 7 days) 1.4. Module 2 Arm 2: screening, cycle 1 day 1, cycle 1 day 8, cycle 2 (and subsequent cycles) day 1, end of treatment, and the 28-day follow-up visit (+/- 7 days) 2. Clinically significant laboratory changes (per NCI CTCAE v5) recorded by the Investigator and trial site staff and evaluated by the Trial Management Group at the following study visits: 2.1. Module 1 dose escalation: screening, cycle 1 day 1 (if more than 14 days since the screening visit have passed), cycle 1 day 8, cycle 2 day 1, cycle 2 day 8, cycle 3 (and any subsequent cycles) day 1 onwards, end of treatment, and the 28-day follow-up visit (+/- 7 days) 2.2. Module 1 dose expansion: screening, cycle 1 day 1 (if more than 14 days since the screening visit have passed), cycle 1 day 8, cycle 1 day 15, Cycle 2 and subsequent cycles day 1, onwards, end of treatment, and the 28-day follow-up visit (+/- 7 days) 2.3. Module 2 Arm 1: screening, cycle 1 day 1 (if more than 14 days since the screening visit have passed), day 8, day 15, day 22, subsequent cycles day 1, day 8, day 15, and day 22, end of treatment, and the 28-day follow-up visit (+/- 7 days) 2.4. Module 2 Arm 2: screening, cycle 1 day 1 (if more than 14 day | — |
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 23/06/2025: Module 1: The occurrence of dose-limiting toxicities (DLTs) at each dosing level recorded by the Investigator and trial site staff during Cycle 1. Module 2: Treatment-emergent adverse events (per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5) during the study period Previous primary outcome measure: The occurrence of dose-limiting toxicities (DLTs) at each dosing level recorded by the Investigator and trial site staff during Cycle 1 | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactLiverpool Clinical Trials Centre -
Outcome results
None listed