A Dose-Escalation and Dose-Expansion Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors

Sponsor

ADC Therapeutics S.A. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05389462

Collaborator

(none)

Enrollment

Locations

Arms

60.6

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to identify the recommended dose for expansion (RDE) (and recommended schedule) and/or the maximum tolerated dose (MTD), and characterize the safety and tolerability of ADCT-601 monotherapy and in combination with gemcitabine.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: ADCT-601 Drug: Gemcitabine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

66 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 13, 2022

Anticipated Primary Completion Date :

Aug 1, 2026

Anticipated Study Completion Date :

Aug 1, 2027

Arms and Interventions

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: ADCT-601 Intravenous (IV) infusion Other Names: Mipasetamab uzoptirine Drug: Gemcitabine Intravenous (IV) infusion
Experimental: Part 1: Dose Escalation, ADCT-601 Monotherapy In Part 1 (dose escalation), participants with selected advanced solid tumors and AXL gene alteration will receive escalating doses of 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 2 groups: Group 1: Participants without gemcitabine in prior lines of therapy Group 2: Participants with gemcitabine containing regimen in prior lines of therapy	Drug: ADCT-601 Intravenous (IV) infusion Other Names: Mipasetamab uzoptirine Drug: Gemcitabine Intravenous (IV) infusion
Experimental: Part 2: Dose Expansion, ADCT-601 Monotherapy In Part 2 (dose expansion), participants with selected advanced solid tumors and AXL gene alteration will receive ADCT-601 monotherapy.	Drug: ADCT-601 Intravenous (IV) infusion Other Names: Mipasetamab uzoptirine

Outcome Measures

Primary Outcome Measures

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

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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of screening:
Selected sarcoma indications from the following 2 separate categories

Soft tissue sarcoma: leiomyosarcoma, liposarcoma, undifferentiated pleomorphic sarcoma (UPS) and synovial sarcoma.
Bone sarcoma: Ewing's sarcoma, osteosarcoma and chondrosarcoma

Participants with AXL gene alteration, with sarcoma (any sarcoma indications, except those listed in ADCT-601 combination therapy arms), ovarian/fallopian tube cancer/primary peritoneal cancer, pancreatic cancer, bladder cancer, cervical cancer, or endometrial cancer.
Participants who are refractory to or intolerant to available standard therapy(ies) known to provide clinical benefit for their condition per Investigator judgment.

In Dose Expansion (Part 2) ADCT-601 combination therapy arm:
Group 1: participants must be gemcitabine naïve
Group 2 participants must have received prior gemcitabine containing regimen

Participants with measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarcoma Oncology Research Center	Santa Monica	California	United States	90403
2	Sarah Cannon at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104