A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 in Participants With Selected Advanced Solid Tumors

A Phase 1, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 as Monotherapy in Patients With Selected Advanced Solid Tumors

The primary objectives of this study are to identify the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), and to characterize the safety and the tolerability of ADCT-901.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ADCT-901

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)
  • Madrid, Spain, 28040
    • (START) Madrid - Hospital Universitario Fundación Jiménez Díaz Location
  • Madrid, Spain, 28041
    • Universidad Complutense de Madrid - Hospital Universitario 12 de Octubre
  • Barcelona
    • Badalona, Barcelona, Spain, 08908
      • Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals Location
• United Kingdom
  • England
    • London, England, United Kingdom, W12 0HS
      • Imperial College Healthcare NHS Trust - St Mary's Hospital
    • London, England, United Kingdom, W1G 6AD
      • Sarah Cannon Research Institute (SCRI) - London (SCRI-UK)
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon at HealthONE
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University, Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Medical Center (UHCMC)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Sarah Cannon at University of Oklahoma Health Sciences Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologic diagnosis of selected solid tumor malignancy that is locally advanced or metastatic at time of Screening: cholangiocarcinoma, ovarian/fallopian tube cancers, prostate cancer, renal cell carcinoma, and triple negative breast cancer (TNBC).

   Note: Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are permitted.

2. Participants who are refractory to or intolerant to existing therapy(ies) known to provide clinical benefit for their condition per Investigator judgment.
3. Participants with measurable disease as determined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1:

Note 1: Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that can be evaluated by cross sectional imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) can be considered as measurable lesions only if the soft tissue component meets the definition of measurability per RECIST v1.1.

Note 2: Prostate cancer participants without measurable lesions will be accepted, with evidence of bone metastatic disease on radiographic examination, whether from bone scan or other imaging modality, and prostate specific antigen (PSA) ≥2.0 ng/mL.

Exclusion Criteria:

1. History of active infection (requiring intravenous [IV] antibiotics, IV antiviral or IV antifungal treatment within 4 weeks of cycle 1, day 1 [C1D1]).
2. Symptomatic central nervous system (CNS) metastases or evidence of leptomeningeal disease (brain MRI or previously documented cerebrospinal fluid cytology). Previously treated asymptomatic CNS metastases are permitted provided that the last treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥4 weeks prior to C1D1 except usage of low dose of steroids on a taper (i.e., up to 10 mg prednisone or equivalent on Day 1 and consecutive days is permissible if being tapered down). Participants with discrete dural metastases are eligible.
3. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or any serosal effusion that is either requiring drainage or associated with shortness of breath).
4. Active diarrhea ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).

5. Active or clinically significant ocular surface disease at baseline. An ocular evaluation is to be confirmed by an ophthalmologist at screening. Participants with any prior episode of cicatricial conjunctivitis (as evaluated by the investigator) are ineligible.

   Note: Mild dry eye syndrome or blepharitis managed with artificial tear drops, without injection or epithelial changes, are not exclusionary.

6. Use of any other experimental medication within 14 days prior to start of study drug (C1D1).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; In Part 1 (dose escalation) participants with selected advanced solid tumors will receive escalating doses of ADCT-901 as monotherapy. Participants can receive ADCT-901 until disease progression, adverse event (AE), or other discontinuation criteria, whichever occurs first.	Drug: ADCT-901; Intravenous infusion
Experimental: Part 2: Dose Expansion; In Part 2 (dose expansion), participants will receive ADCT-901 monotherapy at the dose identified as the RP2D/MTD in Part 1 (dose escalation). Participants will be split into two groups: Group 1: An indication for which ADCT-901 showed in Part 1 to have preliminary activity. Group 2: A group of participants with Part 1 indications, except for the one selected in Group 1 of Part 2. No more than 30% of participants with the same indication are allowed in this basket group. Participants can receive ADCT-901 until disease progression, AE, or other discontinuation criteria, whichever occurs first.	Drug: ADCT-901; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience a Dose Limiting Toxicity (DLT) During the Dose-Escalation Phase		Day 1 to Day 21
Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs)	Adverse events (AEs) and serious adverse events (SAEs) were defined as any untoward medical occurrence in participants whether or not considered related to the investigational medicinal product. Any clinically significant changes in vital signs, laboratory values, 12-lead electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status results will be recorded as AEs and SAEs.	Up to approximately 2.5 years
Number of Participants Who Experience a Dose Interruption		Up to approximately 2.5 years
Number of Participants Who Experience a Dose Reduction		Up to approximately 2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to approximately 2.5 years
Duration of Response (DOR)	Up to approximately 2.5 years
Overall Response Rate (ORR)	Up to approximately 2.5 years
Progression-Free Survival (PFS)	Up to approximately 2.5 years
Maximum Concentration (Cmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Time to Maximum Concentration (Tmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUClast) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Apparent Terminal Elimination Half-Life (Thalf) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Apparent Clearance (CL) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Apparent Volume of Distribution (Vss) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Accumulation Index (AI) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum	Up to approximately 2.5 years
Number of Participants with an Anti-drug Antibody (ADA) Response to ADCT-901	Up to approximately 2.5 years

Collaborators and Investigators

• Sponsor: ADC Therapeutics S.A.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Actual): September 13, 2024
• Study Completion (Actual): September 13, 2024

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; ADCT-901
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ADCT-901-101; 2021-002292-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No