ADCE-D01 for Soft tissue sarcoma

Inclusion criteria

• {"criterion_text":"- Phase 1 Inclusion Criteria: Eligible patients are adults who have selected subtypes of STS with metastatic and/or unresectable disease. Patients must meet all the following criteria to be eligible for the study: ≥ 18 years of age"}
• {"criterion_text":"- Life expectancy of at least 3 months."}
• {"criterion_text":"- Resolution of any toxicities from prior treatment(s) to ≤ Grade 1 by NCI CTCAE v5.0 criteria, or toxicities must have resolved to baseline, prior to first dose of study treatment. Note: unresolved prior treatment-related Grade 2 alopecia, stable Grade 2 peripheral neuropathy, or endocrine disorder adequately managed with hormone replacement therapy (HRT) is allowed."}
• {"criterion_text":"- A male patient must agree to use barrier contraception during the treatment period and for at least 4 months after the last infusion of study treatment, and refrain from donating sperm during this period. Male patients with a pregnant partner must practice sexual abstinence or use a barrier method of contraception (e.g., condom) to prevent exposure of the fetus or neonate."}
• {"criterion_text":"- A female patient is eligible if not pregnant, not breast feeding, and at least one of the following applies: • Not a woman of childbearing potential (WOCBP), or • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 7 months after last infusion of study treatment."}
• {"criterion_text":"- Willing and able to comply with scheduled visits and procedures, drug administration plan, laboratory tests, or other study procedures and study restrictions."}
• {"criterion_text":"- Phase 2 Inclusion Criteria: For Phase 2, the inclusion criteria will be amended based on emerging Phase 1 clinical data and the STS subtypes chosen for the Phase 2 expansion cohorts, as part of a substantial protocol amendment."}
• {"criterion_text":"- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}
• {"criterion_text":"- Histologically confirmed STS with metastatic and/or unresectable disease (not amenable to treatment with curative intent)."}
• {"criterion_text":"- Prior treatment with at least one but no more than two lines of systemic chemotherapy for metastatic/unresectable disease. Prior treatment must include an anthracycline (unless contraindicated or considered unsuitable for treatment with anthracycline). Patients may have received any number of systemic non-cytotoxic therapies. Prior systemic chemotherapy for STS given in a neoadjuvant or adjuvant setting will be considered as one line of therapy if radiological progression occurred either during that treatment or within 3 months of completion, otherwise it will not be counted as a line of treatment. Patient eligibility and appropriateness of study treatment must be discussed within the locally responsible medical team, to ensure that patients have had access to all approved and relevant standard of care treatments from which they are reasonably likely to have derived benefit."}
• {"criterion_text":"- Progressive disease as per Investigator assessment."}
• {"criterion_text":"- At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1."}
• {"criterion_text":"- Availability of tumor tissue at screening. Either: a. An available tumor sample taken within 12 months prior to study entry, from either the primary tumor or metastatic site of disease, or b. A fresh biopsy from a tumor lesion(s) or metastases amenable to biopsy, as confirmed by a radiologist, if appropriate, and as deemed safe by the investigator."}
• {"criterion_text":"- Hematological and biochemical parameters within the following ranges: Hb ≥ 9.0 g/dL; ANC ≥ 1.5 × 10^9/L; Platelet count ≥ 100 × 10^9/L; Total bilirubin ≤ 1.5 × ULN If known Gilbert syndrome: ≤ 3 × ULN; ALT and AST ≤ 2.5 × ULN or ≤ 5 × ULN if raised due to liver metastases Renal function – eGFR by CKD-EPI (2021) ≥ 60 mL/min; Coagulation – PT (or INR) ≤ 1.5 × ULN (if not on anticoagulants). If receiving anticoagulants, the value must be within the therapeutic range for the condition anticoagulated for; Potassium and corrected calcium - Within normal institutional limits"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1."}

Exclusion criteria

• {"criterion_text":"- Phase 1 Exclusion Criteria: Patients who meet any of the following criteria are not eligible for the study: Patients who have had systemic anticancer therapy, including any investigational agent within 4 weeks or 5 half-lives (whichever is shorter) prior to study treatment administration."}
• {"criterion_text":"- Known hypersensitivity to any component of the study medication, excipients, or comparative drugs (e.g., Chinese hamster ovaries, monoclonal antibodies, camptothecin derivatives)."}
• {"criterion_text":"- Primary brain malignancy or known, untreated central nervous system (CNS) or leptomeningeal metastases, or symptoms suggesting CNS involvement for which treatment is required. Screening of asymptomatic patients without history of CNS metastases is not required. Patients with previously treated brain metastases are eligible, provided they have not experienced a seizure, had no significant change in neurological status, and have not required steroids for management of brain metastases in the last 2 weeks prior to enrolment."}
• {"criterion_text":"- Active known second malignancy with the exception of any of the following: • Adequately treated basal cell carcinoma, • Adequately treated Stage 1 cancer from which the patient is currently in remission and has been in remission for ≥ 2 years; • Low-risk prostate cancer with a Gleason score < 7 and a prostate-specific antigen level < 10 ng/mL; • Any other cancer from which the patient has been disease-free for ≥ 3 years. squamous cell carcinoma of the skin, or in situ cervical cancer;"}
• {"criterion_text":"- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment administration, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted prior to study treatment administration provided that the wound has healed."}
• {"criterion_text":"- Ongoing systemic infection requiring treatment with antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed."}
• {"criterion_text":"- Clinically significant cardiovascular disease, defined as any of the following: • Major electrocardiogram (ECG) abnormalities (e.g., symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, clinically significant bundle branch blocks, clinically significant ventricular hypertrophy); • Mean QTc interval value corrected by Fridericia’s formula for heart rate, (QTcF) > 470 msec measured on triplicate ECG; • Major abnormalities documented by echocardiogram (ECHO) (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction < 50%); • Unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months; • Uncontrolled hypertension, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg, which has been confirmed by 2 successive measurements despite optimal medical management; • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 3 months before study treatment administration (except for adequately treated catheter-related venous thrombosis occurring > 1 month prior to study treatment administration)."}
• {"criterion_text":"- Patients with acute infection with human immunodeficiency virus (HIV) 1 or HIV 2. Note: Patients with chronic HIV infection will be eligible if they are considered upon mutual agreement of the investigator and the Sponsor as safe for enrollment and are on an established antiretroviral therapy for at least 28 days and have CD4+ T-cell counts ≥ 350 cells/μL and HIV viral load < 400 copies/mL."}
• {"criterion_text":"- Current active liver disease due to hepatitis B (hepatitis B virus [HBV] surface antigen positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV RNA). Patients with HCV with undetectable virus after treatment are eligible. Patients with a prior history of HBV are eligible if quantitative polymerase chain reaction (qPCR) for HBV DNA is negative."}
• {"criterion_text":"- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on a chest computed tomography (CT) scan at screening."}
• {"criterion_text":"- Presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study."}

Primary endpoints

• {"endpoint_text":"- Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • Incidence of dose-limiting toxicities (DLTs).","definition_or_measurement_approach":"Incidence of DLTs during dose escalation/dose confirmation (Phase 1a/1b) as assessed per protocol-defined DLT criteria."}
• {"endpoint_text":"- Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • Nature, incidence, severity and causality of treatment-emergent adverse events (TEAEs) and changes from baseline in laboratory parameters using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0).","definition_or_measurement_approach":"TEAEs characterized by nature, incidence, severity and causality; laboratory changes assessed using NCI CTCAE v5.0."}
• {"endpoint_text":"- Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • Tolerability as assessed by TEAEs leading to dose interruption, reduction and/or discontinuation.","definition_or_measurement_approach":"Tolerability measured by TEAEs that result in dose interruption, dose reduction, or treatment discontinuation."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • ORR per RECIST v1.1 by Investigator assessment.","definition_or_measurement_approach":"Objective response rate assessed per RECIST v1.1 by Investigator."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • PFS rate at 3 months.","definition_or_measurement_approach":"Progression-free survival rate at 3 months (time-to-event assessment)."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • Nature, incidence, severity and causality of TEAEs and changes from baseline in laboratory parameters using the NCI CTCAE v 5.0.","definition_or_measurement_approach":"Safety and laboratory assessments per NCI CTCAE v5.0."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • Tolerability as assessed by TEAEs leading to dose interruption, reduction and/or discontinuation.","definition_or_measurement_approach":"Tolerability measured by TEAEs resulting in dose interruptions, reductions or discontinuation."}

Secondary endpoints

• {"endpoint_text":"- Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • PK parameters including, but not limited to maximum concentration (Cmax), time to Cmax (Tmax), and area under the concentration-time curve (AUC).","definition_or_measurement_approach":"Pharmacokinetic parameters (e.g., Cmax, Tmax, AUC) measured from plasma concentration-time data."}
• {"endpoint_text":"- Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • Objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), clinical benefit rate (CBR), and time to response (TTR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator assessment.","definition_or_measurement_approach":"Tumor response and time-to-event endpoints assessed per RECIST v1.1 by Investigator."}
• {"endpoint_text":"- Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • overall survival (OS).","definition_or_measurement_approach":"Overall survival measured from date of first study treatment to date of death from any cause."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • DOR, per RECIST v1.1 by Investigator assessment.","definition_or_measurement_approach":"Duration of response per RECIST v1.1 by Investigator assessment."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • PFS, CBR, and TTR, per RECIST v1.1 by Investigator assessment.","definition_or_measurement_approach":"Progression-free survival, clinical benefit rate and time to response assessed per RECIST v1.1 by Investigator."}
• {"endpoint_text":"- Phase 2 (Expansion Cohorts): • OS.","definition_or_measurement_approach":"Overall survival measured as time-to-event (death from any cause)."}

France

Earliest CTIS Part Ii Submission Date

04-04-2025

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

389

Number Of Sites

1

Number Of Participants

54

Belgium

Earliest CTIS Part Ii Submission Date

31-03-2025

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

392

Number Of Sites

1

Number Of Participants

36

Germany

Earliest CTIS Part Ii Submission Date

28-02-2025

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

426

Number Of Sites

1

Number Of Participants

54

Primary sponsor

Full Name

ADCendo ApS

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

codes 1;10;11;12;2;5;6;8;9

Name

Pra International

Responsibilities

code 4

Name

Klifo A/S

Responsibilities

code 14

Name

Celerion Inc.

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG result assessment / ECG analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Travel vendor/Patient reimbursements","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Pra International","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Klifo A/S","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Novasco","duties_or_roles":"Patient reimbursements (French Patients)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes 3;7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"CTI Laboratory Services Spain S.L.","duties_or_roles":"Storage; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"KLIFO A/S","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Medical Image Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Celerion Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"codes 1;10;11;12;2;5;6;8;9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Delfi Diagnostics Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}