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

Phase 1

• Conditions: ocally advanced, unresectable or metastatic solid malignancies; Cancer

• Registration Number: ISRCTN78740398
• Lead Sponsor: Medannex Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-25
• Last Update Posted: 8 July 2024
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

Current 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 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 criteria listed below in addition to the Core Inclusion Criteria:
1. Arm 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.

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Previous inclusion criteria:

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. Negative SARS-CoV-2 reverse transcription polymerase chain reaction (RT PCR) test within 48 hours prior to first receipt of IMP
8. Ability to comply with protocol requirements
9. 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 (i.e., 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 inhi

Exclusion Criteria

Current exclusion criteria as of 28/06/2024:

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 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The occurrence of dose-limiting toxicities (DLTs) at each dosing level recorded by the Investigator and trial site staff during Cycle 1