Solid Tumors (Phase 1)
Conditions
Brief summary
The main purpose of the study is to determine the Maximum Tolerated Dose (MTD), the Recommended Expansion Dose and the safety and tolerability of ADCE-B05 when given as a single therapy over a range of different dose levels.
Detailed description
Safety and tolerability will be evaluated by incidence of DLTs. Efficacy will be evaluated by antitumor activity: ORR, DOR, PFR, and TTR per RECIST v 1.1
Interventions
DRUGADCE-B05
Biological: Antibody-drug conjugate (ADC)
Sponsors
Adcendo ApS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of solid tumor * Advanced disease (i.e., unresectable locally advanced or metastatic) and refractory to, intolerant of, or ineligible for approved therapies * Radiologically or clinically determined progressive disease during or after most recent line of therapy * Measurable disease per RECIST 1.1 * ECOG performance status of 0 or 1 * Adequate hematological and biochemical parameters * 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 * A female patient who is not pregnant, not breast feeding, and either 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
* Treatment with systemic anticancer therapy, including any investigational agent within 3 weeks or 5 half-lives (whichever is shorter) prior to study treatment administration * Prior treatment with an ADC containing a topoisomerase I inhibitor payload * Primary brain malignancy or known, untreated central nervous system (CNS) or leptomeningeal metastases, or symptoms suggesting CNS involvement for which treatment is required * Other malignancy * Major surgical procedure or significant traumatic injury within 28 days prior to study drug administration * Ongoing systemic infection requiring treatment with antibiotics, antivirals, or antimycotics, other than prophylactic treatment * Persistent toxicities from previous systemic anti-neoplastic treatments of Grade \>1 * Clinically significant cardiovascular disease * Acute infection with human immunodeficiency virus (HIV)-1 or HIV-2 * Current active liver disease due to hepatitis B or hepatitis C * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis or pulmonary lymphangitic carcinomatosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the MTD/maximum administered dose of ADCE-B05 | From enrollment to the end of Phase 1a (Approximately 11 months after enrollment) | Incidence of dose-limiting toxicities (DLTs) |
| Assess the safety and tolerability of ADCE-B05 | 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 | The maximum concentration (Cmax) will be assessed to characterize the Pharmacokinetic profile of ADCE-B05 |
| Time to maximum concentration (Tmax) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | The time to maximum concentration (Tmax) will be assessed to characterize the Pharmacokinetic profile of ADCE-B05 |
| Terminal half-life (T[1/2]) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | The terminal half-life (T\[1/2\]) will be assessed to characterize the Pharmacokinetic profile of ADCE-B05 |
| Area under the concentration-time curve (AUC) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | The area under the concentration-time curve (AUC) will be assessed to characterize PK profile of ADCE-B05 |
| Total antibody (TAb) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | The total antibody will be assessed to characterize the Pharmacokinetic profile of ADCE-B05 |
| Free (de-conjugated) payload | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | The free (de-conjugated) payload will be assessed to characterize PK profile of ADCE-B05 |
| Objective response rate (ORR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Objective response rate (ORR) will be assessed by Investigator per RECIST v1.1 to evaluate preliminary antitumor activity |
| Duration of response (DOR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Duration of response DOR will be assessed by Investigator per RECIST v1.1 to evaluate preliminary antitumor activity |
| Progression-free survival (PFS) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | Progression-free survival (PFS) will be assessed by Investigator per RECIST v1.1 to evaluate preliminary antitumor activity |
| Disease Control Rate (DCR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | DCR will be assessed by investigator per RECIST v1.1 to evaluate preliminary antitumor activity |
| Time to Response (TTR) | Throughout the trial duration, completion expected approximately 18 months from completed enrollment | TTR will be assessed by Investigator per RECIST v1.1 to evaluate preliminary antitumor activity |
Countries
Australia, United States
Contacts
CONTACTCharlotte Lybek Lind
CONTACTMargaret McNaull
Outcome results
None listed