💬In plain words
What the trial is, and whether it could suit you
This study is to determine the activity and tolerability of JS207 as a single agent and in combination cohort with chemotherapy. This is an open-labelled, phase Ib/II study of JS207 in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma. The study will comprise of two phases:
* Phase 1b monotherapy: Consisting of a dose escalation and then expansion phase in patients with recurrent/ metastatic (R/M) NPC, who have failed at least 1 prior line of platinum-based chemotherapy, with or without prior treatment with PD1/ PDL1 inhibitor.
* Randomized phase II: Combination of JS207 with capecitabine or paclitaxel in platinum-refractory patients: Patients who have failed one prior line of platinum-based chemotherapy for R/M NPC will be treated with JS207 in combination with capecitabine.
As phase I portion of the study was completed, the starting dose of JS207 for p
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* Known histologically confirmed diagnosis of nasopharyngeal carcinoma
* Measurable disease according to RECIST ver 1.1.
* Age 18 or above and younger than 80 years old; ECOG performance 0 or 1.
* Adequate bone marrow, renal and hepatic reserve, and clotting profile:
1. Absolute neutrophil count ≥ 1.5 × 10\^9 /L; Platelets ≥ 90×10\^9 /L; Hemoglobin \> 9 g/dL.
2. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula).
3. Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN for patients without liver metastases.
4. Total bilirubin ≤ 3.0 × ULN, AST and ALT ≤ 5.0 × ULN for patients with liver metastases.
5. INR and APTT ≤ 1.5 × ULN
6. Electrocardiography (ECG): Friderica-corrected QT interval (QTcF): ≤470 (females) or ≤450 (males) milliseconds without a history of congenital long QT syndrome
* Urine strip test (multistix or dipstick) showing protein ≤2+; if urine protein characterization \>2+, 24 h urine protein quantification is required; if 24 h urine protein quantification \<1 g, it is acceptable;
* Female or male subjects of childbearing potential must agree to have no plans for childbearing and to voluntarily use highly effective contraception with their partner for the duration of the study for up to 6 months after the end of the last dose, and female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the first dose of study medication.
* Prior treatment with PD1/PDL1 inhibitor as part of neoadjuvant treatment or concurrently with radical radiotherapy with curative intent is allowed as long as there is an interval of 6 or more months since administration of the last dose of PD1 inhibitor and more than 12 months since radical radiotherapy +/- concomitant chemotherapy.
* Prior treatment with PD1/PDL1 inhibitor for the first-line treatment of R/N NPC is allowed, as long as there is an interval of 6 or more months since administration of the last dose of PD1/PDL1 inhibitor.
Exclusion Criteria:
* Prior radical RT to the primary NPC within 12 months
* Known history of nasopharyngeal necrosis
* Presence of locoregional tumor recurrence or distant metastatic disease associated with invasion of major vascular structure(s) on imaging which may increase the risk of serious bleeding. This may include (but not limited to) regional neck recurrence invading major vascular structures or ;
* Presence of central lung lesions involving major blood vessels;
* History of clinically significant bleeding defined as Grade 2 epistaxis or Grade 3 bleeding at other sites occurring within 4 weeks prior to the first dose of study drug.
* Prior therapy with anti-vascular agents in any clinical setting, including anti-VEGF antibodies or tyrosine kinase-inhibitors targeting VEGFR.
* Uncontrolled hypertension defined as consistently more than 150/100 mmHg despite adequate medical therapy or history of hypertensive crisis or hypertensive encephalopathy;
* Known history of hypersensitivity to any components of the study drug formulation, or other monoclonal antibodies
* Prior therapy with anti-vascular agents in any clinical setting, including anti-VEGF antibodies, tyrosine kinase-inhibitor agent targeting at VEGFR.
* Patients who are on anticoagulants.
* Presence of significant bleeding tendencies or history of severe coagulation disorders;
* Known history of nasopharyngeal necrosis
* Patients with arteriovenous thrombosis events, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis (except venous thrombosis caused by intravenous catheterization due to early chemotherapy) and pulmonary embolism, occurred within 6 months.
* Patients with urine strip test (multi-stix or dipstick) indicating urine protein \> 2+ will need a 24-hour urine protein collection. They are excluded if the 24-hour urine protein is \>1.0g.
* Presence of symptomatic central nervous system metastases that require use of steroids of dose \> prednisolone 10mg daily or equivalent.
* Presence of active autoimmune disease not related to prior use of PD1/PDL1 inhibitor, that require systemic therapy (e.g., use of corticosteroids or immunosuppressive medications) within 2 years prior to the first dose, including, but not limited to: systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease or vasculitis. However, enrollment is allowed for patients with hypothyroidism, adrenal gland, hypophysis, or pituitary gland dysfunction, or type 1 diabetes mellitus that can be controlled with hormone replacement therapy only or vitiligo or psoriasis not requiring systemic therapy;
* History of interstitial lung disease or prior history of pneumonitis that required immunosuppressive therapy including steroids; patients with a history of Grade 1 radiation pneumonitis are eligible;
* Gastrointestinal (GI) perforation of or fistula involving internal organs or intra-abdominal or thoracic abscesses within 6 months prior to the first dose of study drug;
* Presence of severe, unhealed or open wounds, active ulcers or untreated fractures;
* Presence of significant bleeding tendencies or history of severe coagulation disorders;
* Presence of poorly controlled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure \>100 mmHg) on more than 3 separate readings obtained on different days at the clinic, or history of hypertensive crisis or hypertensive encephalopathy;
* History of immunodeficiency, including a positive test for human immunodeficiency virus (HIV), or a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
* Have serious cardiovascular disease including, but not limited to, myocardial infarction, severe/unstable angina pectoris, myocarditis, pericarditis, congestive heart failure (NYHA cardiac function class ≥ grade 2), clinically s
HealthTeky