A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors
- Registration Number
- NCT05389462
- Lead Sponsor
- ADC Therapeutics S.A.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 128
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Male or female participant aged 18 years or older.
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Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of screening:
Part 1:
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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.
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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:
- Combination therapy arms: Sarcoma indications and PAAD.
- Monotherapy arms: PAAD, NSCLC and solid tumors with AXL expression.
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Participants who are refractory to or intolerant to available standard therapy(ies) known to provide clinical benefit for their condition per Investigator judgment.
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Participants with measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
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PAAD only: Royal Marsden Hospital Prognostic Score 0 - 1.
- History of recent infection requiring intravenous (IV) antibiotics, IV antiviral, or IV antifungal treatment within 4 weeks of Cycle 1 Day 1 (C1D1).
- 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.
- 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).
- 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).
- Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Dose Escalation, ADCT-601 Combination Therapy ADCT-601 In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine. Part 2: Dose Expansion, ADCT-601 Monotherapy ADCT-601 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. Part 1: Dose Escalation, ADCT-601 Monotherapy ADCT-601 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. Part 2: Dose Expansion, ADCT-601 Combination Therapy ADCT-601 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. Part 1: Dose Escalation, ADCT-601 Combination Therapy Gemcitabine In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine. Part 2: Dose Expansion, ADCT-601 Combination Therapy Gemcitabine 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.
- Primary Outcome Measures
Name Time Method Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs) 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.
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
Name Time Method 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 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 Number of Participants With an Anti-drug Antibody (ADA) Response to ADCT-601 Day 1 up to approximately 2 years Duration of Response (DOR) Up to approximately 2 years Overall Survival (OS) Up to approximately 2 years Overall Response Rate (ORR) Up to approximately 2 years Progression-Free Survival (PFS) 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 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 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 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 Number of Participants With Anti-drug Antibody (ADA) Titers to ADCT-601 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
Trial Locations
- Locations (14)
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
Stanford Cancer Center, Stanford Medicine at Stanford University
🇺🇸Stanford, California, United States
University of IOWA
🇺🇸Iowa City, Iowa, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Institut Bergonié
🇫🇷Bordeaux, Gironde, France
Sarah Cannon at University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Institut Léon Bérard
🇫🇷Lyon, France
Vanderbilt University Medical Center (VUMC) - Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Madrid Sanchinarro
🇪🇸Madrid, Spain
Centre Antoine Lacassagne
🇫🇷Nice, France
The Royal Marsden NHS Foundation Trust
🇬🇧London, England, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom