A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Mipasetamab Uzoptirine (ADCT-601) Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Selected Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05389462
• Other study ID #: ADCT-601-102
• Secondary ID: 2021-005566-18
• Status: Recruiting
• Phase: Phase 1
• Start date: July 13, 2022
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: ADC Therapeutics S.A.
• Contact: Contact ADC Therapeutics
• Phone: 954-903-7994
• Email: clinical.trials[@]adctherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to identify the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD), and characterize the safety and tolerability of ADCT-601 monotherapy and in combination with gemcitabine.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: August 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female participant aged 18 years or older.

2. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of screening:

Part 1:

1. Combination therapy arms: Selected sarcoma indications from the following 2 separate categories.

• Soft tissue sarcoma: leiomyosarcoma, liposarcoma, undifferentiated pleomorphic sarcoma (UPS; covering malignant fibrous histiocytoma) and synovial sarcoma.

• Bone sarcoma: Ewing's sarcoma (including extraskeletal), osteosarcoma, and chondrosarcoma.

2. Monotherapy arms:

• Sarcoma indications (including those listed for combination therapy arms) regardless of AXL gene amplification status.

• NSCLC regardless of AXL gene amplification status.

• Solid tumors (lymphomas participants are excluded) with known AXL gene amplification.

Part 2:

1. Combination therapy arms: Sarcoma indications and PAAD.

2. Monotherapy arms: PAAD, NSCLC and solid tumors with AXL expression.

3. Participants who are refractory to or intolerant to available standard therapy(ies) known to provide clinical benefit for their condition per Investigator judgment.

4. Participants with measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.

6. PAAD only: Royal Marsden Hospital Prognostic Score 0 - 1.

Exclusion Criteria:

1. History of recent 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 magnetic resonance imaging [MRI] or previously documented cerebrospinal fluid [CSF] 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 Day 1 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. 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-601
Intravenous (IV) infusion
• Gemcitabine
Intravenous (IV) infusion

Locations

Country	Name	City	State
France	Institut Bergonié	Bordeaux	Gironde
France	Institut Léon Bérard	Lyon
France	Centre Antoine Lacassagne	Nice
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of IOWA	Iowa City	Iowa
United States	Vanderbilt University Medical Center (VUMC) - Ingram Cancer Center	Nashville	Tennessee
United States	Sarah Cannon at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Sarcoma Oncology Research Center	Santa Monica	California
United States	Stanford Cancer Center, Stanford Medicine at Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
ADC Therapeutics S.A.

Countries where clinical trial is conducted

United States,  France,  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) are 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 years
Primary	Number of Participants who Experience a Dose Limiting Toxicity (DLT)		Day 1 to Day 21
Primary	Number of Participants who Experience a Dose Interruption		Up to approximately 2 years
Primary	Number of Participants who Experience a Dose Reduction		Up to approximately 2 years
Secondary	Overall Response Rate (ORR)		Up to approximately 2 years
Secondary	Duration of Response (DOR)		Up to approximately 2 years
Secondary	Progression-Free Survival (PFS)		Up to approximately 2 years
Secondary	Overall Survival (OS)		Up to approximately 2 years
Secondary	Serum Concentration of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199		Day 1 up to approximately 2 years
Secondary	Maximum Concentration (Cmax) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Time to Maximum Concentration (Tmax) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Area Under the Concentration-time Curve from Time Zero to Infinity (AUCinf) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Apparent Terminal Elimination Half-life (T1/2) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Apparent Clearance (CL) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Apparent Steady-state Volume of Distribution (Vss) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Accumulation Index (AI) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum		Day 1 up to approximately 2 years
Secondary	Number of Participants With an Anti-drug Antibody (ADA) Response to ADCT-601		Day 1 up to approximately 2 years
Secondary	Number of Participants With Anti-drug Antibody (ADA) Titers to ADCT-601		Day 1 up to approximately 2 years