Clinical Trials /

Safety, Tolerability, Pharmacokinetics, and Antitumor Study of ADCT-601 to Treat Advanced Solid Tumors

NCT03700294

Description:

This study evaluates the safety, tolerance, pharmacokinetics (PK), and antitumor activity of ADCT-601 in patients with advanced solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Mesothelioma
  • Nasopharyngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, Pharmacokinetics, and Antitumor Study of ADCT-601 to Treat Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-601 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ADCT-601-101
  • NCT ID: NCT03700294

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ADCT-601ADCT-601

Purpose

This study evaluated the safety, tolerance, pharmacokinetics (PK), and antitumor activity of ADCT-601 in patients with advanced solid tumors.

Detailed Description

      This is a Phase 1 open-label, multicenter single-arm study with a dose-escalation phase (Part
      1) followed by a dose-expansion phase (Part 2). The study will enroll approximately 75
      patients. A standard 3+3 dose-escalation design will be used for Part 1 in order to determine
      the MTD and/or recommended dose for expansion (RDE).

      Part 2 will consist of 3 cohorts from one or more selected tumor types. Each cohort will
      enroll 15 patients.

      The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3
      weeks), and a Follow-up Period (visits approximately every 12 weeks for up to 2 years after
      treatment discontinuation).
    

Trial Arms

NameTypeDescriptionInterventions
ADCT-601Experimental
  • ADCT-601

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patient aged 18 years or older.

          2. Pathologic diagnosis of one of the following solid tumor malignancies which is locally
             advanced or metastatic at screening:

               1. Breast cancer which is ER negative, partial response (PR) negative, and HER2
                  negative

               2. Colorectal cancer

               3. Esophageal cancer

               4. Gastric cancer

               5. Head and neck cancer (squamous cell carcinoma and nasopharyngeal carcinoma)

               6. Mesothelioma

               7. Non-small cell lung cancer

               8. Ovarian cancer

               9. Pancreatic cancer

              10. Soft Tissue Sarcomas

          3. Patients with relapsed or refractory disease who have failed, or are intolerant to,
             any established therapy; or for whom no other treatment options are available, in the
             opinion of the Investigator.

          4. Measurable disease per RECIST 1.1.

          5. Patient must agree to biopsy of tumor for study biomarker testing.

          6. Eastern Cooperative Oncology Group performance status, 0 to 1.

          7. Adequate organ function as defined by screening laboratory values within the following
             parameters:

               1. Absolute neutrophil count (ANC) ≥ 1.5 × 103/µL (off growth factors at least 72
                  hours)

               2. Platelet count ≥100 x 103/µL without transfusion

               3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
                  glutamyl transferase (GGT) ≤ 2.5 × the upper limit of normal (ULN); ≤ 5 × ULN if
                  there is liver involvement with tumor

               4. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert's syndrome may have a
                  total bilirubin up to ≤ 3 × ULN)

               5. Blood creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min by
                  the Cockcroft and Gault equation.

          8. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior
             to start of study drug (C1D1) for women of childbearing potential.

          9. 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-601. Men with female partners who are of childbearing potential
             must agree that they 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-601.

        Exclusion Criteria:

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

          2. Active second primary malignancy other than nonmelanoma skin cancers, nonmetastatic
             prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the
             breast, or other malignancy that the Sponsor's medical monitor and Investigator agree
             and document should not be exclusionary.

          3. Active autoimmune disease, including motor neuropathy considered of autoimmune origin
             and other central nervous system (CNS) autoimmune disease. Patients with vitiligo,
             type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
             requiring hormone replacement, psoriasis not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll, provided the trigger can be avoided.

          4. Known seropositive and requiring antiviral therapy for human immunodeficiency virus,
             hepatitis B virus, or hepatitis C virus.

          5. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.

          6. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain MRI or
             previously documented cerebrospinal fluid cytology).

             Previously treated asymptomatic CNS metastases are permitted provided that the last
             treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥ 8
             weeks prior to Day 1 except usage of low dose of steroids on a taper (ie, up to 10 mg
             on Day 1 and consecutive days is permissible if being tapered down). Patients with
             discrete dural metastases are eligible.

          7. Clinically significant third space fluid accumulation (ie, ascites requiring drainage
             or pleural effusion that is either requiring drainage or associated with shortness of
             breath).

          8. Breastfeeding or pregnant.

          9. Significant medical comorbidities, including but not limited to, uncontrolled
             hypertension (blood pressure [BP] ≥ 160/100 mmHg repeatedly), unstable angina,
             congestive heart failure (greater than New York Heart Association class II),
             electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial
             infarction within 6 months prior to screening, uncontrolled atrial or ventricular
             cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease.

         10. Major surgery, radiotherapy, chemotherapy, or other antineoplastic therapy within 14
             days prior to start of study drug (C1D1), except shorter if approved by the Sponsor.

         11. Use of any other experimental medication within 14 days prior to start of study drug
             (C1D1).

         12. Planned live vaccine administration after starting study drug (C1D1).

         13. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE]
             version 4.0) from acute non-hematologic toxicity (Grade ≤ 2 neuropathy or alopecia)
             due to previous therapy prior to screening.

         14. Congenital long QT syndrome or a corrected QTcF interval of > 480 ms at screening
             (unless secondary to pacemaker or bundle branch block).

         15. Any other significant medical illness, abnormality, or condition that would, in the
             Investigator's judgment, make the patient inappropriate for study participation or put
             the patient at risk.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:First 21-day cycle for each patient (dose escalation only)
Safety Issue:
Description:Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to 2 Years
Safety Issue:
Description:According to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR).
Measure:Disease control rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description:According to the RECIST 1.1 defined as the proportion of patients with a BOR of CR, PR, or SD.
Measure:Duration of response (DOR)
Time Frame:Up to 2 years
Safety Issue:
Description:Defined as the time from the documentation of first tumor response to disease progression or death.
Measure:Overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:Defined as the time between the start of treatment and death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:ADC Therapeutics S.A.

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