First-in-Human Study of ADCE-D01 in Soft Tissue Sarcoma (ADCElerate 1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ADCendo ApS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jun 2025 → ongoing

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Adcendo ApS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacokinetic, Others, Safety

Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • To determine the MTD/maximum administered dose and RP2DS of ADCE-D01; • To assess the safety and tolerability of ADCE-D01.
Phase 2 (Expansion Cohorts): • To evaluate the antitumor activity of ADCE-D01 at the RP2DS; • To further characterize the safety and tolerability of ADCE-D01 at the RP2DS.

Secondary objectives 4

1. Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • To characterize the PK profile of ADCE-D01 (Phase 1a only).
2. Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • To evaluate preliminary antitumor activity of ADCE-D01.
3. Phase 2 (Expansion Cohorts): • To further characterize the durability of tumor response of ADCE-D01 at the RP2DS.
4. Phase 2 (Expansion Cohorts): • To further characterize the antitumor activity of ADCE-D01 at the RP2DS.

Conditions and MedDRA coding

Soft Tissue Sarcoma

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Paul-Ehrlich-Institut, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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
2. 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.
3. Histologically confirmed STS with metastatic and/or unresectable disease (not amenable to treatment with curative intent).
4. 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.
5. Progressive disease as per Investigator assessment.
6. At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
7. 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.
8. 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
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Life expectancy of at least 3 months.
11. 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.
12. 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.
13. 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.
14. Willing and able to comply with scheduled visits and procedures, drug administration plan, laboratory tests, or other study procedures and study restrictions.
15. 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.

Exclusion criteria 11

1. 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.
2. Known hypersensitivity to any component of the study medication, excipients, or comparative drugs (e.g., Chinese hamster ovaries, monoclonal antibodies, camptothecin derivatives).
3. 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.
4. 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;
5. 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.
6. Ongoing systemic infection requiring treatment with antibiotic, antiviral, or antifungal treatment. Note: prophylactic treatment is allowed.
7. 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).
8. 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.
9. 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.
10. 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.
11. Presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • Incidence of dose-limiting toxicities (DLTs).
2. 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).
3. Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • Tolerability as assessed by TEAEs leading to dose interruption, reduction and/or discontinuation.
4. Phase 2 (Expansion Cohorts): • ORR per RECIST v1.1 by Investigator assessment.
5. Phase 2 (Expansion Cohorts): • PFS rate at 3 months.
6. 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.
7. Phase 2 (Expansion Cohorts): • Tolerability as assessed by TEAEs leading to dose interruption, reduction and/or discontinuation.

Secondary endpoints 6

1. 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).
2. 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.
3. Phase 1a (Dose Escalation) and Phase 1b (Dose Confirmation): • overall survival (OS).
4. Phase 2 (Expansion Cohorts): • DOR, per RECIST v1.1 by Investigator assessment.
5. Phase 2 (Expansion Cohorts): • PFS, CBR, and TTR, per RECIST v1.1 by Investigator assessment.
6. Phase 2 (Expansion Cohorts): • OS.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ADCendo ApS

Sponsor organisation

ADCendo ApS

Address

Nordre Fasanvej 215

City

Frederiksberg

Postcode

2000

Country

Denmark

Scientific contact point

Organisation

ADCendo ApS

Contact name

Medical monitoring

Public contact point

Organisation

ADCendo ApS

Contact name

Medical monitoring

Third parties 13

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications