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

Exclusion Criteria

• •1. Participation in another investigational interventional study.
• •2. Prior therapy with a CD25 (IL-2R) antibody.
• •3. Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
• •4. Participants 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 \[e.g., Wegener's granulomatosis\]) (participants with vitiligo, type 1 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) caused by a pathogen known to be associated with GBS, for example: herpes simplex virus 1/2 (HSV1, HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• •Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase chain reaction \[PCR\]) were mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional 2 days were allowed in the event of logistical issues for receiving the results on time).
• •8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing was not mandatory to be eligible but should be considered in participants with high risk for these infections; testing was mandatory if status was unknown.
• •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 \[CTCAE version 4.0\]) 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 were permitted provided that the last treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥4 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 were permissible if being tapered down). Participants 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 participants received 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, 4 weeks were indicated as the washout period.
• •19. Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
• •20. Participants 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 within 30 days prior to the first dose of study treatment and during study treatment.
• •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, made the participant inappropriate for study participation or put the participant at risk.
• •25. For participants treated with camidanlumab tesirine in combination with pembrolizumab: patients intolerant to checkpoint-inhibitor or with a history of the following ≥ Grade 3 immune-related adverse events: hepatitis, renal, ocular, neurologic, cardiovascular, rheumatologic, and hematologic.
• •26. For participants treated with camidanlumab tesirine in combination with pembrolizumab: participants with a history of non-infectious pneumonitis related to prior systemic treatment and that require treatment with steroids within the last 6 months prior to enrollment.