Study of ADCT-502 in Patients With Advanced Solid Tumors Withhuman Epidermal Growth Factor Receptor-2 (HER2) Expression

NCT03125200 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ADCT-502-101
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 5

Brief Summary

This study evaluated ADCT-502 in participants with Advanced Solid Tumors with HER2 Expression. Participants participated in a dose-escalation phase (Part 1) and were due to participate in the dose expansion phase (Part 2). In Part 2, patients were due to receive the dose level identified in Part 1, but the study was terminated prior to the beginning of Part 2.

Conditions

Breast Cancer; Non Small Cell Lung Cancer; GastroEsophageal Cancer; Bladder Cancer

Outcome Measures

Primary Outcomes (9)

• Number of Participants Who Experienced Dose-Limiting Toxicities

  Day 1 to 3 Weeks (one cycle)

• Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above

  The Common Terminology Criteria For Adverse Events (CTCAE) Version 4 will be used.

  Day 1 to 3 Weeks (one cycle)

• Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE)

  An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

• Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE)

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

• Number of Participants With Clinically Significant Clinical Laboratory Tests

  Clinical significance was determined by the investigator.

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

• Number of Participants With Clinically Significant Physical Examination Results

  Clinical significance was determined by the investigator.

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

• Number of Participants Who Experience a Clinically Significant Change in Eastern Cooperative Oncology Group (ECOG) Performance Status

  Performance status was assessed using the ECOG performance status grades. These range between Grade 0 (fully active) and Grade 5 (dead). Clinical significance was determined by the investigator.

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

• Number of Participants With Clinically Significant Vital Signs

  Vital sign measurements include arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

• Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results

  Standard 12-lead ECG's will be used. Clinical significance was determined by the investigator.

  Day 1 to end of trial, a maximum of 168 days (+ 30 days)

Secondary Outcomes (18)

• Overall Response Rate (ORR)

  Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks

• Disease Control Rate (DCR)

  Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks

• Duration of Response (DOR)

  Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks

• Progression-Free Survival (PFS)

  Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks

• Overall Survival (OS)

  Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks

Study Arms (1)

ADCT-502

EXPERIMENTAL

Part 1 (dose escalation): Participants received an infusion of ADCT-502, at escalating doses. Part 1 continued until the maximum tolerated dose or the recommended dose(s) and schedule(s) for expansion were determined. Part 2 (expansion): Participants were due to be assigned to the recommended dose level of ADCT-502 as identified in Part 1 by the Dose Escalation Steering Committee.

Drug: ADCT-502

Interventions

ADCT-502 DRUG

Intravenous Infusion

ADCT-502

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 age 18 years or older
• Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
• Eastern Cooperative Oncology Group (ECOG) performance status: Part 1: 0-2, Part 2: 0-1
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block or unstained slides to demonstrate HER2 expression.
• Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening with documented HER2 expression.
• Part 2/Dose Expansion Only: Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥1.5× 109/L).
• Platelet count ≥100,000 //mm3 (≥100 × 109/L).
• Hemoglobin ≥ 9 g/L (≥5.6 mmol/L).
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); or ≤ 5.0 × ULN if liver metastases are present.
• Total bilirubin ≤ 1.5× ULN (or ≤ 3× ULN, with direct bilirubin ≤1.5 × ULN, in participants with known Gilbert syndrome).
• Creatinine ≤ 1.5× ULN; or, if serum creatinine \> 1.5 × ULN, a measured creatinine clearance must be \>60mL/min/1.73m2 as calculated by the Cockcroft and Gault equation for participants to be eligible.
• Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of ADCT-502. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the participant receives his last dose of ADCT-502.

You may not qualify if:

• Known history of ≥ Grade 3 hypersensitivity to a therapeutic antibody.
• Known history of positive serum human anti-drug antibody (ADA) to trastuzumab.
• Major surgical procedure or significant traumatic injury, radiotherapy, chemotherapy, targeted therapy, hormone therapy, or other anticancer therapy.
• Failure to recover to Grade 0 or Grade 1 from acute non-hematologic toxicity due to previous therapy, prior to screening (with the exception of alopecia).
• Central Nervous System (CNS) disease only.
• Symptomatic CNS metastases or evidence of leptomeningeal disease.
• Active cardiovascular disease or significant history thereof.
• Other active disease including but not limited to ulceration of the upper gastrointestinal tract, autoimmune disease, HIV infection, active Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.
• Breastfeeding or pregnant.
• Other concurrent severe and/or uncontrolled medical conditions.

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (5)

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Memorial Hospital

New York, New York, 10065, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Medical Oncology Clinic - Institut Jules Bordet

Brussels, 1000, Belgium

Location

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: ADC Therapeutics
• Organization: ADC Therapeutics

clinical.trials@adctherapeutics.com

954-903-7994

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 24, 2017
• Study Start: May 18, 2017
• Primary Completion: April 5, 2018
• Study Completion: April 5, 2018
• Last Updated: February 1, 2021
• Results First Posted: August 28, 2019

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); BE (1)