Study of ADCT-301 in Patients With Selected Advanced Solid Tumors
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.
- Written informed consent must be obtained prior to any procedures.
- Male or female patient aged 18 years or older.
- 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
- 4. Patients who are refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
- Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST v1.1 or irRC/irRECIST/iRECIST.
- 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.
- ECOG performance status 0-1.
- Adequate organ function as defined by screening laboratory values within the following parameters:
- Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72 h).
- Platelet count ≥100 × 10^3/μL without transfusion in the past 10 days.
- Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed).
- 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.
- 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).
- Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft-Gault equation.
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential.
- 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
- Participation in another investigational interventional study.
- Prior therapy with a CD25 (IL-2R) antibody within the last 4 months.
- Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
- Patients with prior solid organ or allogeneic bone marrow transplant.
- 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).
- 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).
- 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.
- 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.
- History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
- 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.
- 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.
- 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).
- Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
- Active infection requiring systemic antibiotic therapy.
- Active bleeding diathesis or significant anticoagulation (international normalized ratio [INR] ≥2.0).
- Breastfeeding or pregnant.
- 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.
- 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.
- Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
- 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
- Planned live vaccine administration after starting study drug (C1D1).
- Congenital long QT syndrome, or a corrected QTcF interval of ≥ 480 ms, at screening (unless secondary to pacemaker or bundle branch block).
- 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.
- 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
Locations & Contacts
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Trial Objectives and Outline
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 Phase & Type
ADC Therapeutics S.A.
Secondary IDs NCI-2019-00866
Clinicaltrials.gov ID NCT03621982