ADCX-020 for the Treatment of Patients With Locally Advanced or Metastatic Cancers

Official title

A First-in-human, Multicenter Dose Escalation and Multiple Cohort Expansion Phase 1a/b Study to Investigate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ADCX-020 in Participants With Locally Advanced or Metastatic Solid Tumors

Overview

The purpose of this first-in-human study is to explore the safety, pharmacokinetics and effects of the study drug ADCX-020 in patients with advanced and metastatic solid tumors. ADCX-020 is an investigational anticancer therapy called antibody drug conjugate. This study is set up in multiple parts. In the first part of the study, participants receive increasing doses of ADCX-020. Then 2 or more doses will be assessed to identify the optimal dose. This optimal dose is subsequently evaluated for effect on different cancer types.

Detailed description

This is a first-in-human (FIH) open-label, multicenter, dose escalation and multiple cohort expansion Phase 1a/b study to investigate safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of ADCX-020 monotherapy in participants with relapsed or refractory solid tumors, or who are intolerant to standard of care.

During dose escalation, Phase 1a, participants will receive escalating doses of ADCX-020 to identify the MTD based on the observation of DLTs. Intermediate and higher dose levels as well as alternative dosing regimens may be investigated during this part of the study.

Dose expansion, Phase 1b, will be initiated with a dose optimization of ADCX-020 using two or more dose levels of ADCX-020 and/or evaluating a different dosing regimen. Expansion in multiple cohorts is planned for selected patient populations using the RP2D.

Phase 1a will be overseen by a Dose Escalation Committee (DEC) and Phase 1b will be overseen by a Safety Review Committee (SRC).

Interventions

• Drug ADCX-020
  ADC

Primary outcome measures

• Ph1a: To determine the safety and tolerability of ADCX-020 [Time frame: Start of treatment until 30 days after last dose]
• Ph1a: To determine the maximun tolerated dose (MTD) or recommended dose range for expansion and optimization [Time frame: Start of treatment to end of DLT observation period]
• Ph1b: To determine the recommended Phase 2 dose (RP2D) [Time frame: Baseline to 30 days post last study drug administration]
• Ph1b: To assess the objective response rate (ORR) of ADCX-020 [Time frame: Baseline until the date of the first documented disease progression, death, or start of new anticancer therapy (approximately 24 months)]

Secondary outcome measures (9)

• To evaluate duration of objective response (DoR) [Time frame: Baseline until approximately 24 months]
• To evaluate the disease control rate (DCR) [Time frame: Baseline until approximately 24 months]
• To assess prgression free survival (PFS) [Time frame: Baseline until approximately 24 months]
• Phase 1b: To evaluate overall survival (OS) [Time frame: Baseline to approximately 24 months]
• To determine the plasma concentration of ADCX-020 [Time frame: Start of treatment until 30 days after last dose]
• To determine the time to Cmax (Tmax) for ADCX-020 [Time frame: Start of treatment until 30 days after last dose]
• To determine the terminal phase elimination half-life (t1/2) for ADCX-020 [Time frame: Start of treatment until 30 days after last dose]
• To determine the area under the plasma concentration-time curve (AUC) for ADCX-020 [Time frame: Start of treatment until 30 days after last dose]
• To evaluate the immunogenicity of ADCX-020 [Time frame: Start of treatment until 30 days after last dose]

Eligibility criteria

Inclusion criteria

• Male and female participants ≥ 18 years of age
• Ph1a: Locally advanced or metastatic solid tumor relapsed or PD following local standard treatments, for which no standard treatment is available
• Ph1b: Eligible patients should have only received prior lines of systemic therapy according to SoC in the advanced/metastatic setting (not counting neoadjuvant/adjuvant treatment if completed >6 months prior to recurrence)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Radiologically measurable disease by RECIST v1.1
• Mandatory adequate tumor tissue sample available
• Must have recovered from all clinically relevant toxicities from previous cancer therapies (to at least Grade 1, except for alopecia)

Exclusion criteria

• Known allergies/hypersensitivity/intolerance to or contraindication to exatecan, or any excipient
• Phase 1b: Prior antibody drug conjugate exposure with a topoisomerase 1 inhibitor payload
• Uncontrolled or significant cardiac disease including left ventricular ejection fraction (LVEF) <50%, myocardial infarction or uncontrolled/unstable angina
• Has clinically active central nervous system (CNS) metastases
• Has a history of lung fibrosis or non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment
• Other unacceptable abnormalities, medications or procedures as defined by protocol

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 6 centers

• Macquarie University — Sydney
• Blacktown Hospital — Sydney
• Sunshine Coast University Private Hospital — Birtinya
• Tasman Oncology Research — Southport
• Cancer Research SA — Adelaide
• Linear Clinical Research — Nedlands

Spain · 3 centers

• START Barcelona — Barcelona
• START Madrid FJD — Madrid
• START Madrid CIOCC — Madrid

Identifiers

NCT: NCT07238075 · ADCX-020-01 · 2025-523959-65-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗