Clinical trial NCT04972981: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 in Participants With Selected Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors
ADCT-901
Lead sponsor: ADC Therapeutics S.A.
Sponsor class: INDUSTRY
First posted: 2021-07-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 2.5 years
measure: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) During the Dose-Escalation Phase
timeFrame: Day 1 to Day 21
measure: Number of Participants Who Experience a Dose Interruption
timeFrame: Up to approximately 2.5 years
measure: Number of Participants Who Experience a Dose Reduction
timeFrame: Up to approximately 2.5 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 2.5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2.5 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2.5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 2.5 years
measure: Maximum Concentration (Cmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum
timeFrame: Up to approximately 2.5 years
measure: Time to Maximum Concentration (Tmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum
timeFrame: Up to approximately 2.5 years
measure: 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
timeFrame: Up to approximately 2.5 years
measure: 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
timeFrame: Up to approximately 2.5 years
measure: 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
timeFrame: Up to approximately 2.5 years
measure: Apparent Terminal Elimination Half-Life (Thalf) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum
timeFrame: Up to approximately 2.5 years
measure: Apparent Clearance (CL) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum
timeFrame: Up to approximately 2.5 years
measure: Apparent Volume of Distribution (Vss) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum
timeFrame: Up to approximately 2.5 years
measure: Accumulation Index (AI) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum
timeFrame: Up to approximately 2.5 years
measure: Number of Participants with an Anti-drug Antibody (ADA) Response to ADCT-901
timeFrame: Up to approximately 2.5 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon at HealthONE
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Medical Center (UHCMC)
state: Ohio
city: Oklahoma City
country: United States
facility: Sarah Cannon at University of Oklahoma Health Sciences Center
state: Oklahoma
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Badalona
country: Spain
facility: Institut Catala D'oncologia (ICO) - Hospital Duran I Reynals Location
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'hebron - Vall D'hebron Institut D'oncologia (VHIO)
city: Madrid
country: Spain
facility: (START) Madrid - Hospital Universitario Fundación Jiménez Díaz Location
city: Madrid
country: Spain
facility: Universidad Complutense de Madrid - Hospital Universitario 12 de Octubre
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - St Mary's Hospital
state: England
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute (SCRI) - London (SCRI-UK)
state: England
Study officials:
References: