Clinical trial NCT05389462: A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced solid tumors
Mipasetamab uzoptirine
ADCT-601
Sarcoma
Gemcitabine
AXL
Pancreatic cancer
NSCLC
Lead sponsor: ADC Therapeutics S.A.
Sponsor class: INDUSTRY
First posted: 2022-05-25
Enrollment: 128
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 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Number of Participants who Experience a Dose Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 21
measure: Number of Participants who Experience a Dose Interruption
timeFrame: Up to approximately 2 years
measure: Number of Participants who Experience a Dose Reduction
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Serum Concentration of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199
timeFrame: Day 1 up to approximately 2 years
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: Number of Participants With an Anti-drug Antibody (ADA) Response to ADCT-601
timeFrame: Day 1 up to approximately 2 years
measure: Number of Participants With Anti-drug Antibody (ADA) Titers to ADCT-601
timeFrame: Day 1 up to approximately 2 years
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center, Stanford Medicine at Stanford University
state: California
city: Iowa City
country: United States
facility: University of IOWA
state: Iowa
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Oklahoma City
country: United States
facility: Sarah Cannon at University of Oklahoma Health Sciences Center
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (VUMC) - Ingram Cancer Center
state: Tennessee
city: Bordeaux
country: France
facility: Institut Bergonié
state: Gironde
city: Lyon
country: France
facility: Institut Léon Bérard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
Study officials:
References: