First-in-Human Study of ADCE-B05 in Patients With Advanced Solid Tumors

Official title

A First-in-Human, Phase 1a/1b, Open-Label Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of the Antibody Drug Conjugate ADCE-B05 in Patients With Advanced Solid Tumors

Overview

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

• Drug ADCE-B05
  Biological: Antibody-drug conjugate (ADC)

Primary outcome measures

• Determine the MTD/maximum administered dose of ADCE-B05 [Time frame: From enrollment to the end of Phase 1a (Approximately 11 months after enrollment)]
• Assess the safety and tolerability of ADCE-B05 [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]

Secondary outcome measures (11)

• Maximum concentration (Cmax) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Time to maximum concentration (Tmax) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Terminal half-life (T[1/2]) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Area under the concentration-time curve (AUC) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Total antibody (TAb) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Free (de-conjugated) payload [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Objective response rate (ORR) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Duration of response (DOR) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Progression-free survival (PFS) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Disease Control Rate (DCR) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]
• Time to Response (TTR) [Time frame: Throughout the trial duration, completion expected approximately 18 months from completed enrollment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 4 centers

• Scientia Clinical Research — Randwick
• Southern Oncology Clinical Research Unit — Bedford Park
• Monash Health — Clayton
• Peter MacCallum Cancer Centre — Melbourne

United States · 3 centers

• Highlands Oncology Group — Springdale
• Yale University — New Haven
• University Of Texas MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT07362888 · ADCE-B05-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗