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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Gemcitabine; Drug: ADCT-601

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Contact ADC Therapeutics; Phone Number: 954-903-7994; Email: clinical.trials@adctherapeutics.com

Study Locations

• France
  • Lyon, France, 69008
    • Recruiting
    • Institut Léon Bérard
  • Nice, France, 06100
    • Recruiting
    • Centre Antoine Lacassagne
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • Recruiting
      • Institut Bergonié
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebrón
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario Madrid Sanchinarro
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Recruiting
      • Sarcoma Oncology Research Center
    • Stanford, California, United States, 94304
      • Recruiting
      • Stanford Cancer Center, Stanford Medicine at Stanford University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Sarah Cannon at University of Oklahoma Health Sciences Center
      • Contact: Email: phase1-referrals@ouhsc.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center (VUMC) - Ingram Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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).

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation, ADCT-601 Combination Therapy; In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine.	Drug: Gemcitabine; Intravenous (IV) infusion; Drug: ADCT-601; Intravenous (IV) infusion; Other Names: Mipasetamab uzoptirine
Experimental: Part 1: Dose Escalation, ADCT-601 Monotherapy; In Part 1 (dose escalation), participants with sarcoma indications (regardless of AXL gene amplification status), non-small-cell lung cancer (NSCLC) (regardless of AXL gene amplification status), and solid tumors with AXL gene amplification, will receive ADCT-601 monotherapy.	Drug: ADCT-601; Intravenous (IV) infusion; Other Names: Mipasetamab uzoptirine
Experimental: Part 2: Dose Expansion, ADCT-601 Combination Therapy; In Part 2 (dose expansion), participants with selected sarcoma indications will receive ADCT-601 in combination with gemcitabine. Participants will be split into 3 cohorts: Cohorts 5 and 6: Sarcoma indications. Cohort 7: Pancreatic cancer.	Drug: Gemcitabine; Intravenous (IV) infusion; Drug: ADCT-601; Intravenous (IV) infusion; Other Names: Mipasetamab uzoptirine
Experimental: Part 2: Dose Expansion, ADCT-601 Monotherapy; In Part 2 (dose expansion), participants with a selected indication will receive ADCT-601 monotherapy. Participants will be split into cohorts: Cohort 1: Soft tissue sarcoma (STS). Cohort 2: Pancreatic adenocarcinoma (PAAD). Cohort 3: NSCLC. Cohort 4: Solid tumors with known AXL expression.	Drug: ADCT-601; Intravenous (IV) infusion; Other Names: Mipasetamab uzoptirine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of Participants who Experience a Dose Limiting Toxicity (DLT)		Day 1 to Day 21
Number of Participants who Experience a Dose Interruption		Up to approximately 2 years
Number of Participants who Experience a Dose Reduction		Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	Up to approximately 2 years
Overall Response Rate (ORR)	Up to approximately 2 years
Progression-Free Survival (PFS)	Up to approximately 2 years
Overall Survival (OS)	Up to approximately 2 years
Serum Concentration of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199	Day 1 up to approximately 2 years
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
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
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
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
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
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
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
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
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
Number of Participants With an Anti-drug Antibody (ADA) Response to ADCT-601	Day 1 up to approximately 2 years
Number of Participants With Anti-drug Antibody (ADA) Titers to ADCT-601	Day 1 up to approximately 2 years

Collaborators and Investigators

• Sponsor: ADC Therapeutics S.A.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; NSCLC; Pancreatic cancer; Sarcoma; Advanced solid tumors; AXL; Mipasetamab uzoptirine; ADCT-601
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: ADCT-601-102; 2021-005566-18 (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