Metastatic Soft Tissue Sarcoma, Unresectable Soft Tissue Sarcoma
Conditions
Keywords
Phase 1/Phase 2, Sequential, Treatment
Brief summary
The goal of this clinical trial is to learn about the safety, tolerability and efficacy of ADCE-D01.
Detailed description
Safety and Tolerability evaluated by incidence of DLTs. Efficacy evaluated by antitumor activity; ORR, DOR, PFS, CBR and TTR per RECIST v i.1.
Interventions
BIOLOGICALAntibody-drug conjugate (ADC)
ADCE-D01 is an antibody-drug conjugate (ADC) composed of an anti-urokinase plasminogen activator receptor-associated protein (uPARAP) antibody, AB-004, conjugated to a topoisomerase I inhibitor, P1021, via a protease cleavage tetra-peptide linker.
Sponsors
Adcendo ApS
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥ 18 years of age 2. Histologically confirmed STS with metastatic and/or unresectable disease (not amenable to treatment with curative intent). 3. Prior treatment with at least one but no more than two lines of cytotoxic systemic therapy for metastatic/unresectable disease. 4. Measurable disease as per RECIST v 1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life expectancy of at least 3 months. 7. 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. 8. A female patient is eligible if not pregnant, not breast feeding, and not a woman of childbearing potential (WOCBP), or agrees to follow the contraceptive guidance during the treatment period and for at least 7 months after last infusion of study treatment.
Exclusion criteria
1. 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. Primary brain malignancy or known, untreated central nervous system (CNS) or leptomeningeal metastases, or symptoms suggesting CNS involvement. 3. Clinically significant cardiovascular disease 4. Patients with acute infection with human immunodeficiency virus (HIV) 1 or HIV 2. 5. Current active liver disease due to hepatitis B 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the MTD/maximum administered dose and RP2DS of ADCE-D01. | From enrollment to the end of Phase 1b (Approximately 18 months after enrollment) | Measuring incidence of dose-limiting toxicities (DLTs) |
| Assess the safety and tolerability of ADCE-D01 | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | 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). Tolerability as assessed by TEAEs leading to dose interruption, reduction and/or discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Cmax) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Time to maximum plasma concentration will be assessed to inform ADCE-D01 PK profile |
| ADCE-D01 time to Cmax (Tmax) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Time to Cmax (Tmax) will be assessed to characterize the ADCE-D01 PK profile |
| ADCE-D01 area under the concentration-time curve (AUC) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | ADCE-D01 area under the concentration-time curve (AUC) will be assessed to characterize PK profile |
| Evaluate ADCE-D01 objective response rate (ORR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Objective response rate (ORR) per RECIST v1.1 by Investigator assessment |
| Evaluate ADCE-D01 duration of response (DOR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Duration of response DOR, measured per RECIST v1.1 by Investigator assessment will be used to further characterize the durability of tumor response of ADCE-D01 |
| ADCE-D01 progression-free survival (PFS) | Throughout the trial duration, completion expected approximately 18 months from completed enrollmen | Progression-free survival (PFS) assessed by Investigator per RECIST v1.1 to evaluate preliminary antitumor activity. |
| ADCE-D01 clinical benefit rate (CBR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | clinical benefit rate (CBR) assessed by Investigator per RECIST version 1.1 to evaluate preliminary antitumor activity of ADCE-D01 |
| ADCE-D01 time to response (TTR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | time to response (TTR) assessed by Investigator per RECIST version 1.1 to evaluate preliminary antitumor activity of ADCE-D01 |
Countries
Belgium, France, Germany, United Kingdom, United States
Contacts
CONTACTRené Smrčka
CONTACTMargaret McNaull
Outcome results
None listed