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

NCT05389462 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: ADCT-601-1022021-005566-18
• Study Type: interventional
• Target: 128
• Locations: 4 countries
• Sites: 14

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.

Conditions

Advanced Solid Tumors

Keywords

Advanced solid tumors; Mipasetamab uzoptirine; ADCT-601; Sarcoma; Gemcitabine; AXL; Pancreatic cancer; NSCLC

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (16)

• Overall Response Rate (ORR)

  Up to approximately 2 years

• Duration of Response (DOR)

  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

Study Arms (4)

Part 1: Dose Escalation, ADCT-601 Combination Therapy

EXPERIMENTAL

In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine.

Drug: ADCT-601; Drug: Gemcitabine

Part 1: Dose Escalation, ADCT-601 Monotherapy

EXPERIMENTAL

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

Part 2: Dose Expansion, ADCT-601 Combination Therapy

EXPERIMENTAL

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: ADCT-601; Drug: Gemcitabine

Part 2: Dose Expansion, ADCT-601 Monotherapy

EXPERIMENTAL

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

Interventions

ADCT-601 DRUG

Intravenous (IV) infusion

Also known as: Mipasetamab uzoptirine

Part 1: Dose Escalation, ADCT-601 Combination Therapy; Part 1: Dose Escalation, ADCT-601 Monotherapy; Part 2: Dose Expansion, ADCT-601 Combination Therapy; Part 2: Dose Expansion, ADCT-601 Monotherapy

Gemcitabine DRUG

Intravenous (IV) infusion

Part 1: Dose Escalation, ADCT-601 Combination Therapy; Part 2: Dose Expansion, ADCT-601 Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participant aged 18 years or older.
• Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of screening:
• Part 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.
• 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.
• Participants who are refractory to or intolerant to available standard therapy(ies) known to provide clinical benefit for their condition per Investigator judgment.
• Participants with measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

You may not qualify if:

• 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).

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (14)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Stanford Cancer Center, Stanford Medicine at Stanford University

Stanford, California, 94305, United States

Location

University of IOWA

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Sarah Cannon at University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 78229, United States

Location

Vanderbilt University Medical Center (VUMC) - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Institut Bergonié

Bordeaux, Gironde, 33076, France

Location

Institut Léon Bérard

Lyon, 69008, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

The Royal Marsden NHS Foundation Trust

London, England, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma; Pancreatic Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: May 25, 2022
• Study Start: July 13, 2022
• Primary Completion: April 17, 2025
• Study Completion: April 17, 2025
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); GB (2); US (6); ES (3)