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

NCT05389462
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Phase
Phase 1
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Recruitment status
Terminated
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Participants
128
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Lead sponsor
ADC Therapeutics S.A.
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Start date
2022-07-13
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Number of sites
14
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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.
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Short title
A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Terminated
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Phase
Phase 1
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Study type
Interventional
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Reason stopped
Sponsor decided to halt further development of ADCT-601
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Completion date
2025-04-17
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First posted
2022-05-25
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Registry last updated
2025-05-22
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Primary completion date
2025-04-17
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Start date
2022-07-13
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Actual participants
128
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Participants
128
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Participant count basis
Actual
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Protocol amendments
6
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Number of sites
14
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
ADC Therapeutics S.A.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05389462
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ClinicalTrials.gov ID
NCT05389462
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs)

    Timeframe: Up to approximately 2 years

    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.

  2. Number of Participants who Experience a Dose Limiting Toxicity (DLT)

    Timeframe: Day 1 to Day 21

  3. Number of Participants who Experience a Dose Interruption

    Timeframe: Up to approximately 2 years

  4. Number of Participants who Experience a Dose Reduction

    Timeframe: Up to approximately 2 years

  1. Overall Response Rate (ORR)

    Timeframe: Up to approximately 2 years

  2. Duration of Response (DOR)

    Timeframe: Up to approximately 2 years

  3. Progression-Free Survival (PFS)

    Timeframe: Up to approximately 2 years

  4. Overall Survival (OS)

    Timeframe: Up to approximately 2 years

  5. Serum Concentration of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199

    Timeframe: Day 1 up to approximately 2 years

  6. Maximum Concentration (Cmax) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum

    Timeframe: Day 1 up to approximately 2 years

  7. Time to Maximum Concentration (Tmax) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum

    Timeframe: Day 1 up to approximately 2 years

  8. 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

    Timeframe: Day 1 up to approximately 2 years

  9. 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

    Timeframe: Day 1 up to approximately 2 years

  10. 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

    Timeframe: Day 1 up to approximately 2 years

  11. Apparent Terminal Elimination Half-life (T1/2) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum

    Timeframe: Day 1 up to approximately 2 years

  12. Apparent Clearance (CL) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum

    Timeframe: Day 1 up to approximately 2 years

  13. Apparent Steady-state Volume of Distribution (Vss) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum

    Timeframe: Day 1 up to approximately 2 years

  14. Accumulation Index (AI) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum

    Timeframe: Day 1 up to approximately 2 years

  15. Number of Participants With an Anti-drug Antibody (ADA) Response to ADCT-601

    Timeframe: Day 1 up to approximately 2 years

  16. Number of Participants With Anti-drug Antibody (ADA) Titers to ADCT-601

    Timeframe: Day 1 up to approximately 2 years

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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.

  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).
Sources for eligibility
clinicaltrials.gov

  • Sarcoma Oncology Research CenterSanta Monica, United States
  • Stanford Cancer Center, Stanford Medicine at Stanford UniversityStanford, United States
  • University of IOWAIowa City, United States
  • Washington University School of MedicineSt Louis, United States
  • Sarah Cannon at University of Oklahoma Health Sciences CenterOklahoma City, United States
  • Vanderbilt University Medical Center (VUMC) - Ingram Cancer CenterNashville, United States
  • Institut BergoniéBordeaux, France
  • Institut Léon BérardLyon, France
  • Centre Antoine LacassagneNice, France
  • Hospital Universitario Vall d'HebronBarcelona, Spain
  • Hospital Universitario Fundacion Jimenez DiazMadrid, Spain
  • Hospital Universitario Madrid SanchinarroMadrid, Spain
  • The Royal Marsden NHS Foundation TrustLondon, United Kingdom
  • The Christie NHS Foundation TrustManchester, United Kingdom
Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2021-005566-18
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (2)

Targets (14)