SUPPORT HOTLINE (888) 901-2226
Donate Now

BRIEF TITLE: A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-502 in Patients With Advanced Solid Tumors With HER2 Expression

A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-502 in Patients With Advanced Solid Tumors With HER2 Expression


  • Org Study ID: ADCT-502-101
  • Secondary ID:
  • NCT ID: NCT03125200
  • NCT Alias:
  • Sponsor: ADC Therapeutics S.A. - Industry
  • Source: ADC Therapeutics S.A.

Brief Summary

This study evaluates ADCT-502 in patients with Advanced Solid Tumors with HER2 Expression. Patients will participate in a dose-escalation phase (Part 1) and dose expansion (Part 2). In Part 2, patients will receive the dose level identified in Part 1.

Detailed Description


Study ADCT-502-101 is the first clinical study with ADCT-502 in patients with Advanced Solid
Tumors with HER2 Expression.

ADCT-502 is an antibody drug conjugate (ADC) composed of an engineered version of the
humanized monoclonal antibody trastuzumab, directed against the human HER2 receptor,
conjugated to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. ADCT-502 specifically binds to
HER2, and once internalized, releases the PBD dimer to allow cross-linking of DNA and
eventually trigger cell death.

The study will be conducted in 2 parts. In Part 1 (dose escalation) patients will receive an
infusion of ADCT-502, at escalating doses. Part 1 will continue until the maximum tolerated
dose or the recommended dose(s) and schedule(s) for expansion are determined. In Part 2
(expansion), patients will be assigned to the recommended dose level of ADCT-502 identified
in Part 1 by the Dose Escalation Steering Committee.

For each patient, the study will include a screening period (up to 28 days), a treatment
period, and a follow-up period to assess disease progression and survival for up to 12 weeks
after the last dose of study drug. The total study duration will be dependent on overall
patient tolerability to the study drug and response to treatment as patients may continue
treatment until disease progression or unacceptable toxicity. It is anticipated that the
duration of the entire study (Parts 1 and 2) could be approximately 3 years from first
patient treated to last patient completed.

Overal Status Start Date Phase Study Type
Recruiting May 12, 2017 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Assessment of Dose Limiting Toxicities (DLT) of ADCT-502.

Primary Outcome 1 - Time Frame: 21 Day Cycle

Primary Outcome 2 - Measure: Determination of the ADCT-502 Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE)

Primary Outcome 2 - Time Frame: 21 Day Cycle

Condition:

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

Eligibility

Criteria:
Main Inclusion Criteria:

- 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 patients
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 patient 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 patient receives his last dose of ADCT-502.

Main Exclusion Criteria:

- Known history of ≥ Grade 3 hypersensitivity to a therapeutic antibody.

- Known history of positive serum human 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 HBV and HCV
infection.

- Breastfeeding or pregnant.

- Other concurrent severe and/or uncontrolled medical conditions.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Jens Wuerthner

Phone: +41.(0)21.653 02 00

Email: Jens.Wuerthner@adctherapeutics.com

Locations

Facility Status Contact
Stanford Cancer Center
Palo Alto, California 94304
United States
Recruiting
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Recruiting
Memorial Sloan Kettering Memorial Hospital
New York, New York 10065
United States
Recruiting
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas 78229
United States
Recruiting
Medical Oncology Clinic - Institut Jules Bordet
Brussels, 1000
Belgium
Recruiting