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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: ADCT-601
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participant aged 18 years or older. - US only: for sarcoma participants in combination therapy and monotherapy arms: ≥ 16 years. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of screening: 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. 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 - 1. 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).

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation, ADCT-601 Combination Therapy<br>In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine. | Drug: ADCT-601<br>* Intravenous (IV) infusion<br>* Other names: Mipasetamab uzoptirine;Drug: Gemcitabine<br>* Intravenous (IV) infusion<br>|
| Experimental: Part 1: Dose Escalation, ADCT-601 Monotherapy<br>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<br>* Intravenous (IV) infusion<br>* Other names: Mipasetamab uzoptirine;|
| Experimental: Part 2: Dose Expansion, ADCT-601 Combination Therapy<br>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<br>* Intravenous (IV) infusion<br>* Other names: Mipasetamab uzoptirine;Drug: Gemcitabine<br>* Intravenous (IV) infusion<br>|
| Experimental: Part 2: Dose Expansion, ADCT-601 Monotherapy<br>In Part 2 (dose expansion), participants with a selected indication will receive ADCT-601 monotherapy. | Drug: ADCT-601<br>* Intravenous (IV) infusion<br>* Other names: Mipasetamab uzoptirine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoma, Gemcitabine, AXL, Advanced solid tumors, Mipasetamab uzoptirine, ADCT-601