Be Part of Research - Trial Details - The first-in-human trial of MDX-124 in patients with advanced cancer

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This study aims to find an effective dose of the study drug (MDX-124) for future studies. The research will look at how safe and well the body copes with the drug before any severe side effects appear (tolerability) and examine how this drug may work with existing forms of treatment available.
The study drug is a molecule involved within the immune system that can specifically bind to a target and activate an immune response (antibody). These antibodies are based on human antibodies (humanised) and have been changed to specifically target a protein called annexin-A1 (ANXA1). All antibodies used will be exactly the same (monoclonal). These are referred to as humanised monoclonal antibodies. The study drug binds to a protein produced by humans and animals called ANXA1.
ANXA1 is a protein produced by various organs in the human body and has several normal functions, but when overproduced is known to play a critical role in how certain cancers behave.

Adults with solid tumours

You can take part if:

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.

You may not be able to take part if:

Current exclusion criteria as of 23/06/2025:Core1. 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 has received previous systemic anticancer therapy for advanced pancreatic adenocarcinoma. Patients receiving adjuvant or neoadjuvant treatment and completed ≥ 6 months prior to registration are eligible.2. History of allergic reactions attributed to previous gemcitabine or nab-paclitaxel treatment.3. Known contraindication to any of the excipients of gemcitabine or nab-paclitaxel.4. History of posterior reversible encephalopathy syndrome (PRES).5. Participants with a high cardiovascular risk including but not limited to a history of myocardial infarction within the last 5 years or with significant cardiac arrhythmias requiring medication or pacemaker.6. Participants who take drugs that inhibit or induce CYP3A4.7. History of (non-infectious) pneumonitis or has current pneumonitis.8. Previous radiotherapy for measurable lesions.

Arm 2:1. Participant has received more than 1 line of prior systemic therapy with chemotherapy.- Prior adjuvant and/or neoadjuvant treatment is not exclusionary.- Treatment with a targeted therapy (e.g. IDH1 and/or FGFR2 inhibitors) is not exclusionary.2. Ampullary carcinoma is excluded.3. 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. Prior immunotherapy within 42 days of the first administration of IMP.

Previous exclusion criteria as of 28/06/2024: Core1. 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 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 last dose of IMP.12. History or presence of alcoholism or drug abuse within the past 2 years.

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 short cycle of palliative radiotherapy for bone pain) or other targeted therapy administered within 28 days of first receipt of IMP.1.1. For immunotherapy within 42 days of first administration of IMP.1.2. For targeted hormone therapy within 14 days of first administration of IMP. Patients on standard-of-care hormonal therapies may continue that therapy.1.3. For nitrosoureas and mitomycin C therapy within 42 days of 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 has received previous systemic anticancer therapy for advanced pancreatic adenocarcinoma. Patients receiving adjuvant or neoadjuvant treatment and completed ≥ 6 months prior to registration are eligible.2. History of allergic reactions attributed to previous gemcitabine or nab-paclitaxel treatment.3. Known contraindication to any of the excipients of gemcitabine or nab-paclitaxel.4. History of posterior reversible encephalopathy syndrome (PRES).5. Participants with a high cardiovascular risk including but not limited to a history of myocardial infarction within the last 5 years or with significant cardiac arrhythmias requiring medication or pacemaker.

_____

Previous exclusion criteria:

Core1. 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 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.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 last dose of IMP. 12. History or presence of alcoholism or drug abuse within the past 2 years.

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 short cycle of palliative radiotherapy for bone pain) or other targeted therapy within 28 days of first receipt of IMP.1.1. For immunotherapy within 42 days of first administration of IMP.1.2. For hormone therapy within 14 days of first administration of IMP.1.3. For nitrosoureas and mitomycin C therapy within 42 days of 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 has received previous systemic anticancer therapy for advanced pancreatic adenocarcinoma. Patients receiving adjuvant or neoadjuvant treatment and completed ≥ 6 months prior to randomisation are eligible.2. History of allergic reactions attributed to previous gemcitabine or nab-paclitaxel treatment. 3. Known contraindication to any of the excipients of gemcitabine or nab-paclitaxel.4. History of posterior reversible encephalopathy syndrome (PRES). 5. Participants with a high cardiovascular risk including but not limited to a history of myocardial infarction within the last 5 years or with significant cardiac arrhythmias requiring medication or pacemaker.

Participants may derive clinical benefits following treatment with the study drug (MDX-124), which is not currently available other than via participation in the trial. Participants will receive increased medical care (including blood tests and scans) as part of participation in the trial.
Participation in the study will enable the potential benefits and side effects of MDX-124 to be assessed which will then inform future research.
To date, there is limited knowledge of MDX-124's safety profile in humans. The study has been designed to mirror the treatment and clinical assessments carried out as part of the standard of care in this group of patients. In addition, as this is a first-in-human study, additional cytokine (Module 1 dose escalation) and immunophenotyping lab tests have been included in the schedule of events.
1. Administration of MDX-124
2. Taking part in sample collection
3. Informed consent
4. Radiation exposure when receiving scans
1. Assessment of full blood count, renal function and liver function will be made prior to each administration of MDX-124
2. The occurrence of toxicity including haematological toxicity which requires dose adjustment will be specified in the protocol
3. The effect of exposure to MDX-124 in patients with renal impairment is not known. Therefore, trial entry is restricted to patients with an estimated glomerular filtration rate (eGFR) ≥50 ml/min/1.73m2.
4. MDX-124 should not be administered to pregnant women. A negative pregnancy test should be confirmed before the administration of MDX-124 for all women of childbearing age.
5. Subjects will be asked to remain at the site for 6 hours post-dose on Cycle 1 Day 1 in order for them to be observed by study staff.
6. There is no known antidote for MDX-124 and treatment of AEs associated with its use should be for the underlying adverse symptoms
7. Since MDX-124 will be prepared in specialist oncology pharmacies and administered by experienced chemotherapy-trained nurses via intravenous infusion, overdose is considered to be highly unlikely. There is no specific treatment for an overdose of MDX-124. In case of overdose, therapy may be interrupted and any adverse reactions treated symptomatically.
Plasma and serum will be taken prior to the start of treatment and at every dosing visit of every cycle. In addition, blood samples will be collected for PK, annexin-A1, cytokine (Module 1 dose escalation), immunophenotyping, tumour marker and immunogenicity analysis.
When the needle is inserted to draw the blood the patients may feel moderate pain, or only a prick or stinging sensation and afterwards there may be some throbbing or slight bruising.
The total number of PK samples collected per participant will be 24 in Module 1 and 22 in Module 2. This will require subjects to remain at the site for 6 hours after receiving administration of MDX-124 on 2 separate days (Module 1 dose escalation) and having to return to the site on no treatment days for sample collection.
Tissue collection is not compulsory in Module 1 of the study but is part of the study for Module 2. Patients can either agree or disagree to take part. Complications with biopsies are uncommon. In a small number of cases, there may be some bleeding from the biopsy site. This is usually minor and soon stops. There is also a risk of inflammation at the site of the biopsy but again this is rare. There is a slight risk that the small wound will become infected by the biopsy.
Some CT scans may need special preparation beforehand, called contrast medium. Iodinated contrast is generally safe. At the time of administration patients may:
1. Feel hot and flushed for a minute or two
2. Have a metallic taste in the mouth
3. Feel like they are passing urine but they aren’t – this feeling is common and passes quickly
Rarely people have an allergic reaction to the contrast medium. This most often starts with weakness, sweating and difficulty breathing. The radiographer will ask for any allergies before the contrast medium is administered.
Patients might get a small bruise around the area where they put the needle in.
There's a risk that the contrast medium will leak outside the vein. This can cause swelling and pain in the hand or arm but it’s rare.
There is a small risk that the contrast medium can affect the kidneys. The radiographer will check the most recent blood test results before the scan to make sure the kidneys are working well.
The study is only to be conducted at hospitals with expertise in the treatment and diagnosis of advanced cancer to ensure the highest standard of care for the patients.

The first-in-human trial of MDX-124 in patients with advanced cancer

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Age: Adult

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The first-in-human trial of MDX-124 in patients with advanced cancer

Recruiting

Open to: All Genders

Age: Adult

Medical Conditions

Study summary

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Study Details

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Where can I take part?

Possible Benefits and Risks

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We'd like your feedback

This page is to help you find out about a research study and if you may be able to take part