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

ADC Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Gemcitabine; Drug: ADCT-601

Study type: Interventional

Funder types: Industry

Identifiers

NCT05389462

ADCT-601-102

2021-005566-18 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 260 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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260 participants in 4 patient groups

Part 1: Dose Escalation, ADCT-601 Combination Therapy

Experimental group

Description:

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

Treatment:

Drug: ADCT-601

Drug: Gemcitabine

Part 1: Dose Escalation, ADCT-601 Monotherapy

Experimental group

Description:

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.

Treatment:

Drug: ADCT-601

Part 2: Dose Expansion, ADCT-601 Combination Therapy

Experimental group

Description:

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.

Treatment:

Drug: ADCT-601

Drug: Gemcitabine

Part 2: Dose Expansion, ADCT-601 Monotherapy

Experimental group

Description:

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.

Treatment:

Drug: ADCT-601