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Written informed consent must be obtained prior to any procedures |
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Male or female patient aged 18 years or older |
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Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening |
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Part 1 Dose escalation camidanlumab tesirine as monotherapy |
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Selected advanced solid tumors: colorectal, head and neck, NSCLC, gastric and |
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esophageal cancers, pancreas, bladder, renal cell carcinoma, melanoma, TNBC |
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and ovarian/fallopian tube cancers |
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Part 1 Dose-escalation camidanlumab tesirine in combination with |
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pembrolizumab |
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Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer |
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ovarian /fallopian tube cancer, pancreatic cancer, non-small cell lung cancer |
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and melanoma |
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Part 2 Dose expansion camidanlumab tesirine in combination with pembrolizumab |
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Note: For colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube |
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Group 1: One of the indications identified in Part 1, for which at least 1 response (PR or CR) was seen |
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cancer, pancreatic cancers mismatch repair (MMR) / microsatellite stability |
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(MSS) / microsatellite instability (MSI) status is mandatory. If MMR/MSS/MSI |
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parameters |
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status is not available at signature of the informed consent, the test should |
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be performed before Cycle 1 Day 1 (C1D1) |
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Group 2: Patients with advanced solid tumors and MSI-H/dMMR status, who have received a prior regimen containing PD-1/PD-L1 inhibitors, for which the best response was CR, PR, or SD ≥4 months, and then progressed while under treatment with the PD-1/PD-L1 inhibitor-based regimen |
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Note: A maximum of 4 patients with the same indication will be allowed in this basket |
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group |
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Patients who are refractory to or intolerant of existing therapy(ies) known to provide |
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clinical benefit for their condition |
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Patients with advanced/metastatic cancer, with measurable disease as determined by |
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RECIST v1.1 or immune-related Response Criteria (irRC)/ immune-related Response |
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Evaluation Criteria In Solid Tumors (irRECIST)/ immune-related Response Evaluation |
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Criteria In Solid Tumors (iRECIST)/ immune-modified Response Evaluation Criteria in |
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Solid Tumors (imRECIST) as per Investigator discretion |
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A) For camidanlumab tesirine as monotherapy: Patient must have a site of disease |
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amenable to biopsy and be willing to undergo fresh biopsy procedures (minimum 3 passes |
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each) prior to first dose, according to the treating institution's guidelines |
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B) Patients included in the paired-biopsy cohort must in addition be willing to |
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undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 |
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dose of study drug |
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C) For camidanlumab tesirine in combination with pembrolizumab: Patient must either |
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have a site of disease amenable to biopsy and must provide fresh tumor biopsy prior to |
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C1D1, or have sufficient available archival tumor tissue (biopsied after their last |
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disease progression, and in the situation where the patient has received no additional |
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anti-cancer therapy between their progression and C1D1). Patients must also be willing |
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to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 |
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dose of study treatment, according to the treating institution's guidelines |
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ECOG performance status 0-1 |
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Patient with life expectancy ≥ 3 months as per Investigator assessment |
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Adequate organ function as defined by screening laboratory values within the following |
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Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72 |
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hours) |
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Platelet count ≥100 × 10^3/μL without transfusion in the past 10 days |
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Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed) |
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Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma |
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glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN) if there is no |
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liver involvement; ALT or AST ≤5 × ULN if there is liver involvement |
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Total bilirubin ≤1.5 × ULN (patients with known Gilbert's syndrome may have a |
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total bilirubin up to ≤3 × ULN with direct bilirubin ≤1.5 × ULN) |
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Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the |
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Cockcroft-Gault equation |
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Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior |
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to start of study drug for women of childbearing potential (WOCBP) |
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Women of childbearing potential must agree to use a highly effective method of |
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contraception from the time of giving informed consent until at least 9.5 months after |
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the last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab |
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whichever is the latest. Men with female partners who are of childbearing potential |
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must agree to use a condom when sexually active or practice total abstinence from the |
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time of giving informed consent until at least 6.5 months after the patient receives |
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his last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab |
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whichever is the latest |
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Participation in another investigational interventional study
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Patients with prior solid organ or allogeneic bone marrow transplant
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Prior therapy with a CD25 (IL-2R) antibody
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Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody
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History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic
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progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome
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autoimmune vasculitis [e.g., Wegener's granulomatosis]) (patients with vitiligo, type
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diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition
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only requiring hormone replacement may be enrolled)
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History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy
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including Guillain-Barré syndrome and myasthenia gravis) or other central nervous
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system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
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History of recent infection (within 4 weeks of C1D1) caused by a pathogen known to be
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associated with GBS, for example: herpes simplex virus 1/2 (HSV1, HSV2), varicella
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zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles
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Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter
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jejuni, enterovirus D68, or severe acute respiratory syndrome coronavirus 2
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replacement dose steroids in the setting of adrenal insufficiency
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(SARS-CoV-2)
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Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase
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chain reaction [PCR]) are mandatory and must be negative before initiating study
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treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional
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days are allowed in the event of logistical issues for receiving the results on
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time)
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Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV)
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virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing is not
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mandatory to be eligible but should be considered in patients with high risk for these
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infections; testing is mandatory if status is unknown
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History of Stevens-Johnson syndrome or toxic epidermal necrolysis
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Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events version
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0 [CTCAE version 4.0]) from acute nonhematologic toxicity (to ≤Grade 2 for
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neuropathy or alopecia), due to previous therapy, prior to screening
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Symptomatic CNS metastases or evidence of leptomeningeal disease (brain MRI or
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previously documented cerebrospinal fluid [CSF] cytology). Previously treated
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asymptomatic CNS metastases are permitted provided that the last treatment (systemic
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anticancer therapy and/or local radiotherapy) was completed ≥4 weeks prior to Day 1
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except usage of low dose of steroids on a taper (i.e., up to 10 mg prednisone or
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equivalent on Day 1 and consecutive days is permissible if being tapered down)
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Patients with discrete dural metastases are eligible
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Clinically significant third space fluid accumulation (i.e., ascites requiring
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drainage or pleural effusion that is either requiring drainage or associated with
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shortness of breath)
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Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic diarrhea
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(such as irritable bowel syndrome, inflammatory bowel disease)
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Active infection requiring systemic antibiotic therapy
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Active bleeding diathesis or significant anticoagulation (international normalized
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ratio [INR] ≥2.0)
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Breastfeeding or pregnant
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Significant medical comorbidities, including uncontrolled hypertension (blood pressure
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[BP] ≥160 mmHg systolic and/or ≥110 mmHg diastolic repeatedly with or without anti
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hypertensive medication), unstable angina, congestive heart failure (greater than New
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York Heart Association class II), electrocardiographic evidence of acute ischemia
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coronary angioplasty or myocardial infarction within 6 months prior to screening
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severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled
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diabetes, active ulceration of the upper gastrointestinal (GI) tract or GI bleeding
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or severe chronic pulmonary disease
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Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14
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days prior to start of study drug (C1D1), except shorter if approved by the Sponsor
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For cytotoxic agents that have major delayed toxicity, e.g., mitomycin C and
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nitrosoureas, 4 weeks is indicated as washout period. For patients receiving systemic
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anticancer immunotherapies (as opposed to intralesional) that lead to activation of
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Teffs and/or increase the Teff/Treg ratio, such as anti-PD-1 antibodies, 4 weeks are
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indicated as the washout period
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Use of any other experimental medication within 14 days prior to start of study drug
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(C1D1)
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Patients requiring concomitant immunosuppressive agents or chronic treatment with
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corticosteroids except
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topical, inhaled, nasal, and ophthalmic steroids are allowed
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Planned live vaccine within 30 days prior to the first dose of study treatment and
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during study treatment
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Congenital long QT syndrome, or a corrected QTcF interval of ≥ 480 ms, at screening
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(unless secondary to pacemaker or bundle branch block)
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Active second primary malignancy other than non-melanoma skin cancers, non-metastatic
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prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the
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breast, or other malignancy that the Sponsor's medical monitor and Investigator agree
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and document should not be exclusionary
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Any other significant medical illness, abnormality, or condition that would, in the
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Investigator's judgment, make the patient inappropriate for study participation or put
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the patient at risk
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For patients treated with camidanlumab tesirine in combination with pembrolizumab
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patients intolerant to checkpoint-inhibitor or with a history of the following ≥ Grade
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immune-related adverse events: hepatitis, renal, ocular, neurologic, cardiovascular
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rheumatologic, and hematologic
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For patient treated with camidanlumab tesirine in combination with pembrolizumab
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patients with a history of non-infectious pneumonitis related to prior systemic
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treatment and that require treatment with steroids within the last 6 months prior to
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enrollment
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