Clinical Trials /

Study of ADCT-301 in Patients With Selected Advanced Solid Tumors

NCT03621982

Description:

This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Esophagogastric Carcinoma
  • Head and Neck Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of ADCT-301 in Patients With Selected Advanced Solid Tumors
  • Official Title: A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) in Patients With Selected Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ADCT-301-103
  • NCT ID: NCT03621982

Conditions

  • Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content
  • Head and Neck Cancer
  • Non-small Cell Lung Cancer
  • Gastric Cancer
  • Esophageal Cancer
  • Pancreas Cancer
  • Bladder Cancer
  • Renal Cell Carcinoma
  • Melanoma
  • Triple-negative Breast Cancer
  • Ovarian Cancer

Interventions

DrugSynonymsArms
ADCT-301Camidanlumab tesirineADCT-301

Purpose

This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

Detailed Description

      This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose
      expansion part.

      The duration of the study participation for each patient is defined as the time from the date
      of signed written informed consent to the completion of the follow-up period, withdrawal of
      consent, loss to follow-up, or death, whichever occurs first.

      The study will include a Screening Period (of up to 28 days), a Treatment Period (with cycles
      of 3 weeks for a Q3W dosing regimen), and a Follow-up Period (approximately every 12 week
      visits) for up to 1 year after treatment discontinuation
    

Trial Arms

NameTypeDescriptionInterventions
ADCT-301ExperimentalIn Part 1 (dose-escalation), patients will receive a 1-hour intravenous infusion of ADCT-301 on Day 1 every 3 weeks (21-day cycle). 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 receive the recommended dose(s) of ADCT-301 as determined by the Dose Escalation Steering Committee (DESC). This study will investigate dose levels between 20 μg/kg and 300 μg/kg Q3W.
  • ADCT-301

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent must be obtained prior to any procedures.

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

          3. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic
             at time of Screening:

             Part 1 (Dose-Escalation):

             Advanced solid tumors with literature evidence of CD25(+) Treg content, i.e., head and
             neck, non-small cell lung cancer, gastric and esophageal cancers, pancreas, bladder,
             renal cell carcinoma, melanoma, triple negative breast cancer, and ovarian cancers.

             Part 2 (Dose-Expansion):

             Advanced solid tumors literature evidence of CD25(+) Treg content:

               -  Group 1: One of the indications identified in Part 1, for which at least 1
                  response (PR or CR) was seen.

               -  Group 2: Any indication allowed in Part 1, except for the one selected for Group
                  1.

          4. Patients who are refractory to or intolerant of existing therapy(ies) known to provide
             clinical benefit for their condition.

          5. Patients with advanced/metastatic cancer, with measurable disease as determined by
             RECIST v1.1 or irRC/irRECIST/iRECIST.

          6. Patient must have a site of disease amenable to biopsy and be willing to undergo fresh
             biopsy procedures (minimum 3 passes each) prior to first dose, according to the
             treating institution's guidelines.

          7. ECOG performance status 0-1.

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

               1. Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72
                  h).

               2. Platelet count ≥100 × 10^3/μL without transfusion in the past 10 days.

               3. Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed).

               4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma
                  glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN) if there is no
                  liver involvement; ALT or AST ≤5 × ULN if there is liver involvement.

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

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

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

         10. 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 camidanlumab tesirine. Men with female partners who are 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 patient
             receives his last dose of camidanlumab tesirine

        Exclusion Criteria:

          1. Participation in another investigational interventional study.

          2. Prior therapy with a CD25 (IL-2R) antibody within the last 4 months.

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

          4. Patients with prior solid organ or allogeneic bone marrow transplant.

          5. History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic
             progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome,
             autoimmune vasculitis [e.g., Wegener's granulomatosis]) (subjects with vitiligo, type
             I diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition
             only requiring hormone replacement may be enrolled).

          6. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy
             including Guillain-Barré syndrome and myasthenia gravis) or other central nervous
             system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis).

          7. History of recent infection (within 4 weeks of C1D1) considered to be caused by one of
             the following pathogens: herpes simplex virus 1/2 (HSV1, HSV2), varicella zoster
             (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika
             virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, or enterovirus
             D68.

          8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV)
             virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing is not
             mandatory to be eligible but should be considered in patients with high risk for these
             infections.

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

         10. Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events version
             4.0 [CTCAE v4.0]) from acute nonhematologic toxicity (to ≤Grade 2 for neuropathy or
             alopecia), due to previous therapy, prior to screening.

         11. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain 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 ≥8 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).
             Patients with discrete dural metastases are eligible.

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

         13. Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic diarrhea
             (such as irritable bowel syndrome, inflammatory bowel disease).

         14. Active infection requiring systemic antibiotic therapy.

         15. Active bleeding diathesis or significant anticoagulation (international normalized
             ratio [INR] ≥2.0).

         16. Breastfeeding or pregnant.

         17. Significant medical comorbidities, including uncontrolled hypertension (blood pressure
             [BP] ≥160 mmHg systolic and/or ≥110 mmHg diastolic repeatedly with or without anti
             hypertensive medication), 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,
             severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled
             diabetes, active ulceration of the upper gastrointestinal (GI) tract or GI bleeding,
             or severe chronic pulmonary disease.

         18. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14
             days prior to start of study drug (C1D1), except shorter if approved by the Sponsor.
             For cytotoxic agents that have major delayed toxicity, e.g., mitomycin C and
             nitrosoureas, 4 weeks is indicated as washout period. For patients receiving systemic
             anticancer immunotherapies (as opposed to intralesional) that lead to activation of
             Teffs and/or increase the Teff/Treg ratio, such as anti-PD-1 antibodies, 5 half-lives
             are indicated as the washout period.

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

         20. Patients requiring concomitant immunosuppressive agents or chronic treatment with
             corticosteroids except:

               -  replacement dose steroids in the setting of adrenal insufficiency

               -  topical, inhaled, nasal, and ophthalmic steroids are allowed

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

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

         23. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic
             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.

         24. 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:Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose Dose Limiting toxicities as defined per protocol, as related to ADCT-301
Time Frame:The protocol-defined assessment period is one 21-day cycle
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Evaluate the preliminary anti-tumor activity of camidanlumab tesirine
Time Frame:Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days)
Safety Issue:
Description:Overall response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and iRECIST
Measure:Evaluate the preliminary anti-tumor activity of camidanlumab tesirine
Time Frame:Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days)
Safety Issue:
Description:Duration of response (DOR) defined as the time from the first documentation of tumor response to disease progression or death
Measure:Evaluate the preliminary anti-tumor activity of camidanlumab tesirine
Time Frame:Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days)
Safety Issue:
Description:Progression-free survival (PFS) defined as the time between start of treatment and the first documentation of recurrence, progression, or death
Measure:Evaluate the preliminary anti-tumor activity of camidanlumab tesirine
Time Frame:Disease assessments will occur 6 weeks and 12 weeks after Cycle 1 Day 1, then every 12 weeks (cycle = 21 days)
Safety Issue:
Description:Overall survival (OS) defined as the time between the start of treatment and death from any cause
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of the maximum concentration (Cmax)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of the time to maximum concentration (Tmax)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of the accumulation index (AI)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of clearance (CL)
Measure:Pharmacokinetics and Pharmacodynamics assessment- camidanlumab tesirine in serum
Time Frame:Blood sample collection on Day 1, 3, 5, 8 and 15 for Cycles 1 and 2; Day 1 for Cycles 3 and 4; Day 1 for every other subsequent cycle (cycle = 21 days)
Safety Issue:
Description:Noncompartmental analysis of volume of distribution (Vd)
Measure:Evaluate the immunogenicityof camidanlumab tesirine
Time Frame:Blood sample collection on Day 1 and Day 15 for Cycle 1 and Day 1 only for Cycle 2,Cycle 3,Cycle 4 and then Day 1 of every other cycle (cycle = 21 days)
Safety Issue:
Description:Anti-drug antibody (ADA) titers in serum

Details

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

Trial Keywords

  • Camidanlumab tesirine

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