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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04972981
• Other study ID #: ADCT-901-101
• Secondary ID: 2021-002292-19
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 9, 2021
• Est. completion date: April 5, 2025

Study information

• Verified date: January 2024
• Source: ADC Therapeutics S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 132
• Est. completion date: April 5, 2025
• Est. primary completion date: April 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• ADCT-901
Intravenous infusion

Locations

Country	Name	City	State
Spain	Institut Catala D'oncologia (ICO) - Hospital Duran I Reynals Location	Badalona	Barcelona
Spain	Hospital Universitari Vall D'hebron - Vall D'hebron Institut D'oncologia (VHIO)	Barcelona
Spain	(START) Madrid - Hospital Universitario Fundación Jiménez Díaz Location	Madrid
Spain	Universidad Complutense de Madrid - Hospital Universitario 12 de Octubre	Madrid
United Kingdom	Imperial College Healthcare NHS Trust - St Mary's Hospital	London	England
United Kingdom	Sarah Cannon Research Institute (SCRI) - London (SCRI-UK)	London	England
United States	Emory University, Winship Cancer Institute	Atlanta	Georgia
United States	Northwestern University	Chicago	Illinois
United States	University Hospitals of Cleveland Medical Center (UHCMC)	Cleveland	Ohio
United States	Sarah Cannon at HealthONE	Denver	Colorado
United States	Yale Cancer Center	New Haven	Connecticut
United States	Sarah Cannon at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ADC Therapeutics S.A.

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Participants Who Experience a Dose Limiting Toxicity (DLT) During the Dose-Escalation Phase		Day 1 to Day 21
Primary	Number of Participants Who Experience a Dose Interruption		Up to approximately 2.5 years
Primary	Number of Participants Who Experience a Dose Reduction		Up to approximately 2.5 years
Secondary	Overall Response Rate (ORR)		Up to approximately 2.5 years
Secondary	Duration of Response (DOR)		Up to approximately 2.5 years
Secondary	Progression-Free Survival (PFS)		Up to approximately 2.5 years
Secondary	Overall Survival (OS)		Up to approximately 2.5 years
Secondary	Maximum Concentration (Cmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Up to approximately 2.5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Apparent Clearance (CL) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Up to approximately 2.5 years
Secondary	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
Secondary	Accumulation Index (AI) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Up to approximately 2.5 years
Secondary	Number of Participants with an Anti-drug Antibody (ADA) Response to ADCT-901		Up to approximately 2.5 years