{
"info": {
"nct_id": "NCT06525220",
"official_title": "A Phase 3 Randomized, Open-label Study to Evaluate the Efficacy and Safety of Petosemtamab Plus Pembrolizumab Vs Pembrolizumab in First-line Treatment of Recurrent or Metastatic PD-L1+ Head and Neck Squamous Cell Carcinoma",
"inclusion_criteria": "1. Signed ICF before initiation of any study procedures\n2. Age ≥ 18 years at signing of ICF\n3. Histologically confirmed HNSCC with evidence of metastatic or locally recurrent disease not amenable to local therapy with curative intent.\n4. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.\n5. HNSCC patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1.\n6. HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting\n7. A baseline new tumor sample unless the patient has an available tumor sample as an FFPE block with sufficient material.\n8. Measurable disease as defined by RECIST v1.1 by radiologic methods.\n9. ECOG Performance Status (PS) of 0-1\n10. Life expectancy ≥ 12 weeks, as per investigator assessment.\n11. Left ventricular ejection fraction (LVEF) ≥50% or ≥ institutional normal limit, whichever is higher, by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.\n12. Adequate organ function as defined per protocol.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
"exclusion_criteria": "1. Central nervous system metastases that are untreated or already treated but symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 21 days of study entry.\n2. Known leptomeningeal involvement\n3. Any systemic anticancer therapy within 4 weeks of the first dose of study treatment\n4. Major surgery or radiotherapy within 3 weeks of the first dose of study treatment\n5. Persistent Grade >1 clinically significant toxicities related to prior cancer therapies (except for alopecia); stable sensory neuropathy Grade ≤2 National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 is allowed.\n6. History of hypersensitivity reaction to any of the excipients of petosemtomab or pembrolizumab.\n7. Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment; or history of myocardial infarction within 6 months of study entry\n8. History of prior malignancies, with the exception of excised local cancer, or treated cancer deemed at low risk for recurrence with no evidence of disease for ≥3 years\n9. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy\n10. Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders\n11. Patients with known infectious diseases as per protocol.\n12. Pregnant or breastfeeding patients.\n13. The patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to the first dose\n14. The patient has an active autoimmune disease that has required systemic immune suppressive treatment in the past 2 years; replacement therapy is not considered immune suppressive treatment.\n15. Patient has a primary tumor site of nasopharynx, or sinonasal carcinoma (any histology)\n\nOther protocol defined inclusion/exclusion criteria may apply.",
"miscellaneous_criteria": ""
},
"inclusion_lines": [
{
"identified_line": {
"line": "1. Signed ICF before initiation of any study procedures",
"criterions": [
{
"exact_snippets": "Signed ICF",
"criterion": "informed consent form (ICF)",
"requirement": {
"requirement_type": "signed",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Signed ICF",
"criterion": "informed consent form (ICF)",
"requirement": {
"requirement_type": "signed",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "2. Age ≥ 18 years at signing of ICF",
"criterions": [
{
"exact_snippets": "Age ≥ 18 years",
"criterion": "age",
"requirement": {
"requirement_type": "minimum age",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "years"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Age ≥ 18 years",
"criterion": "age",
"requirement": {
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"expected_value": {
"operator": ">=",
"value": 18,
"unit": "years"
}
}
}
]
}
},
{
"identified_line": {
"line": "4. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.",
"criterions": [
{
"exact_snippets": "HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.",
"criterion": "HNSCC primary tumor location",
"requirement": {
"requirement_type": "location",
"expected_value": [
"oropharynx",
"oral cavity",
"hypopharynx",
"larynx"
]
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.",
"criterion": "HNSCC primary tumor location",
"requirement": {
"requirement_type": "location",
"expected_value": [
"oropharynx",
"oral cavity",
"hypopharynx",
"larynx"
]
}
}
]
}
},
{
"identified_line": {
"line": "5. HNSCC patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1.",
"criterions": [
{
"exact_snippets": "HNSCC patients",
"criterion": "HNSCC",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "eligible to receive pembrolizumab as 1L monotherapy",
"criterion": "pembrolizumab eligibility",
"requirement": {
"requirement_type": "eligibility",
"expected_value": true
}
},
{
"exact_snippets": "tumors expressing PD-L1",
"criterion": "PD-L1 expression",
"requirement": {
"requirement_type": "expression",
"expected_value": true
}
},
{
"exact_snippets": "CPS ≥1",
"criterion": "CPS",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">=",
"value": 1,
"unit": "N/A"
}
}
}
]
},
"logical_structure": {
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{
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"criterion": "HNSCC",
"requirement": {
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"expected_value": true
}
},
{
"exact_snippets": "eligible to receive pembrolizumab as 1L monotherapy",
"criterion": "pembrolizumab eligibility",
"requirement": {
"requirement_type": "eligibility",
"expected_value": true
}
},
{
"exact_snippets": "tumors expressing PD-L1",
"criterion": "PD-L1 expression",
"requirement": {
"requirement_type": "expression",
"expected_value": true
}
},
{
"exact_snippets": "CPS ≥1",
"criterion": "CPS",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">=",
"value": 1,
"unit": "N/A"
}
}
}
]
}
},
{
"identified_line": {
"line": "6. HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting",
"criterions": [
{
"exact_snippets": "HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting",
"criterion": "previous systemic therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
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"exact_snippets": "HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting",
"criterion": "previous systemic therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "7. A baseline new tumor sample unless the patient has an available tumor sample as an FFPE block with sufficient material.",
"criterions": [
{
"exact_snippets": "baseline new tumor sample",
"criterion": "baseline new tumor sample",
"requirement": {
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"expected_value": true
}
},
{
"exact_snippets": "available tumor sample as an FFPE block",
"criterion": "available tumor sample as an FFPE block",
"requirement": {
"requirement_type": "availability",
"expected_value": true
}
},
{
"exact_snippets": "sufficient material",
"criterion": "sufficient material",
"requirement": {
"requirement_type": "quantity",
"expected_value": "sufficient"
}
}
]
},
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"condition": {
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{
"exact_snippets": "available tumor sample as an FFPE block",
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"requirement_type": "availability",
"expected_value": true
}
},
{
"exact_snippets": "sufficient material",
"criterion": "sufficient material",
"requirement": {
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}
}
]
},
"then_criteria": null,
"else_criteria": {
"exact_snippets": "baseline new tumor sample",
"criterion": "baseline new tumor sample",
"requirement": {
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"expected_value": true
}
}
}
},
{
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"line": "8. Measurable disease as defined by RECIST v1.1 by radiologic methods.",
"criterions": [
{
"exact_snippets": "Measurable disease as defined by RECIST v1.1",
"criterion": "measurable disease",
"requirement": {
"requirement_type": "definition",
"expected_value": "RECIST v1.1"
}
},
{
"exact_snippets": "by radiologic methods",
"criterion": "radiologic methods",
"requirement": {
"requirement_type": "usage",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Measurable disease as defined by RECIST v1.1",
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"expected_value": "RECIST v1.1"
}
},
{
"exact_snippets": "by radiologic methods",
"criterion": "radiologic methods",
"requirement": {
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"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "9. ECOG Performance Status (PS) of 0-1",
"criterions": [
{
"exact_snippets": "ECOG Performance Status (PS) of 0-1",
"criterion": "ECOG Performance Status",
"requirement": {
"requirement_type": "range",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 0,
"unit": "N/A"
},
{
"operator": "<=",
"value": 1,
"unit": "N/A"
}
]
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "ECOG Performance Status (PS) of 0-1",
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"requirement": {
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"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 0,
"unit": "N/A"
},
{
"operator": "<=",
"value": 1,
"unit": "N/A"
}
]
}
}
}
]
}
},
{
"identified_line": {
"line": "10. Life expectancy ≥ 12 weeks, as per investigator assessment.",
"criterions": [
{
"exact_snippets": "Life expectancy ≥ 12 weeks",
"criterion": "life expectancy",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"operator": ">=",
"value": 12,
"unit": "weeks"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Life expectancy ≥ 12 weeks",
"criterion": "life expectancy",
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"expected_value": {
"operator": ">=",
"value": 12,
"unit": "weeks"
}
}
}
]
}
},
{
"identified_line": {
"line": "12. Adequate organ function as defined per protocol.",
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{
"exact_snippets": "Adequate organ function",
"criterion": "organ function",
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}
}
]
},
"logical_structure": {
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{
"exact_snippets": "Adequate organ function",
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}
}
]
}
},
{
"identified_line": {
"line": "Healthy volunteers allowed",
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{
"exact_snippets": "Healthy volunteers allowed",
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}
}
]
},
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{
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}
}
]
}
},
{
"identified_line": {
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{
"exact_snippets": "minimum age of 18 Years",
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"expected_value": {
"operator": ">=",
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"unit": "Years"
}
}
}
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{
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}
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}
],
"exclusion_lines": [
{
"identified_line": {
"line": "1. Central nervous system metastases that are untreated or already treated but symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 21 days of study entry.",
"criterions": [
{
"exact_snippets": "Central nervous system metastases",
"criterion": "central nervous system metastases",
"requirement": {
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"expected_value": "untreated"
}
},
{
"exact_snippets": "Central nervous system metastases",
"criterion": "central nervous system metastases",
"requirement": {
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"expected_value": "symptomatic"
}
},
{
"exact_snippets": "Central nervous system metastases",
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"requirement": {
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"surgery",
"continued steroid therapy"
]
}
},
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"operator": "<=",
"value": 21,
"unit": "days"
}
}
}
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{
"and_criteria": [
{
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"criterion": "central nervous system metastases",
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}
},
{
"exact_snippets": "Central nervous system metastases",
"criterion": "central nervous system metastases",
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}
}
]
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{
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"surgery",
"continued steroid therapy"
]
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"unit": "days"
}
}
}
]
}
]
}
},
{
"identified_line": {
"line": "2. Known leptomeningeal involvement",
"criterions": [
{
"exact_snippets": "Known leptomeningeal involvement",
"criterion": "leptomeningeal involvement",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"not_criteria": {
"exact_snippets": "Known leptomeningeal involvement",
"criterion": "leptomeningeal involvement",
"requirement": {
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"expected_value": true
}
}
}
},
{
"identified_line": {
"line": "3. Any systemic anticancer therapy within 4 weeks of the first dose of study treatment",
"criterions": [
{
"exact_snippets": "systemic anticancer therapy within 4 weeks of the first dose of study treatment",
"criterion": "systemic anticancer therapy",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": "<=",
"value": 4,
"unit": "weeks"
}
}
}
]
},
"logical_structure": {
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"exact_snippets": "systemic anticancer therapy within 4 weeks of the first dose of study treatment",
"criterion": "systemic anticancer therapy",
"requirement": {
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"operator": "<=",
"value": 4,
"unit": "weeks"
}
}
}
}
},
{
"identified_line": {
"line": "4. Major surgery or radiotherapy within 3 weeks of the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Major surgery ... within 3 weeks of the first dose of study treatment",
"criterion": "major surgery",
"requirement": {
"requirement_type": "time since procedure",
"expected_value": {
"operator": "<",
"value": 3,
"unit": "weeks"
}
}
},
{
"exact_snippets": "radiotherapy within 3 weeks of the first dose of study treatment",
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"unit": "weeks"
}
}
}
]
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{
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"unit": "weeks"
}
}
},
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"criterions": [
{
"exact_snippets": "Persistent Grade >1 clinically significant toxicities related to prior cancer therapies (except for alopecia)",
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"expected_value": true
}
},
{
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"criterion": "clinically significant toxicities related to prior cancer therapies",
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"unit": "N/A"
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"requirement": {
"requirement_type": "exclusion",
"expected_value": [
"alopecia"
]
}
},
{
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"criterion": "stable sensory neuropathy",
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"requirement_type": "grade",
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"value": 2,
"unit": "N/A"
}
}
},
{
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"criterion": "stable sensory neuropathy",
"requirement": {
"requirement_type": "stability",
"expected_value": true
}
}
]
},
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"and_criteria": [
{
"and_criteria": [
{
"and_criteria": [
{
"and_criteria": [
{
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{
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},
{
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"criterions": [
{
"exact_snippets": "History of hypersensitivity reaction to any of the excipients of petosemtomab",
"criterion": "hypersensitivity reaction to excipients of petosemtomab",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "History of hypersensitivity reaction to any of the excipients of ... pembrolizumab",
"criterion": "hypersensitivity reaction to excipients of pembrolizumab",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
},
"logical_structure": {
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{
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"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "History of hypersensitivity reaction to any of the excipients of ... pembrolizumab",
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"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "7. Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment; or history of myocardial infarction within 6 months of study entry",
"criterions": [
{
"exact_snippets": "Unstable angina",
"criterion": "unstable angina",
"requirement": {
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"expected_value": false
}
},
{
"exact_snippets": "history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria",
"criterion": "congestive heart failure",
"requirement": {
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"expected_value": false
}
},
{
"exact_snippets": "history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria",
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"requirement_type": "severity",
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{
"operator": ">=",
"value": 2,
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{
"operator": "<=",
"value": 4,
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}
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"exact_snippets": "serious cardiac arrhythmia requiring treatment",
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"requirement_type": "treatment requirement",
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},
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"exact_snippets": "history of myocardial infarction within 6 months of study entry",
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},
{
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{
"operator": "<=",
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{
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{
"exact_snippets": "Unstable angina",
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"requirement_type": "presence",
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}
]
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},
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{
"operator": "<=",
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},
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"requirement_type": "presence",
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{
"exact_snippets": "treated cancer deemed at low risk for recurrence",
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"requirement_type": "recurrence risk",
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"operator": ">=",
"value": 3,
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}
}
]
},
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},
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},
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},
{
"exact_snippets": "other diseases requiring continuous oxygen therapy",
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},
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}
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"exact_snippets": "uncontrolled active infection",
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"exact_snippets": "clinically significant pulmonary ... disorders",
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"requirement_type": "clinical significance",
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},
{
"exact_snippets": "clinically significant ... metabolic ... disorders",
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},
{
"exact_snippets": "clinically significant ... psychiatric disorders",
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}