protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT02799602 | 16.5 | List of strong CYP3A4 inducers | 16.5 List of strong CYP3A4 inducers
Strong Ajmaline phenobarbital Carbamazepine Enzalutamide Fosphenytoin Hypericum perforatum (St. John's Wort) Lumacaftor Methylphenobarbital Mitotane Phenobarbital Phenytoin Primidone Propranolol phenobarbital Rifabutin Rifampicin Rifamycin Rifapentin | [
"Strong"
] |
NCT02903914 | 1.0 | SAFETY REPORTING CONTACT | 1.0 SAFETY REPORTING CONTACT | Incyte TelerX | | |---------------|--| | | | SAE Reporting Details (to be used for submitting the SAE forms): Safety Fax: Email: | [] |
NCT02903914 | 2.0 | LIST OF ABBREVIATIONS | 2.0 LIST OF ABBREVIATIONS | Abbreviation or Term1 | Definition/Explanation | |-----------------------|------------------------------------------------| | AE | Adverse event | | ALK | Anaplastic Lymphoma Kinase | | ALT | Alanine aminotransferase | | APTT | Activated partial thromboplastin time | | ARG1 | Arginase1 gene ... | [
"CORE PROTOCOL"
] |
NCT02903914 | 3.0 | OBJECTIVES | 3.0 OBJECTIVES | Primary Objectives | Primary Endpoints | | | |-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------... | [] |
NCT02903914 | 4.0 | POTENTIAL RISKS AND BENEFITS OF THE TREATMENT REGIMEN | 4.0 POTENTIAL RISKS AND BENEFITS OF THE TREATMENT REGIMEN | [] |
NCT02903914 | 4.1 | Potential Risks of INCB001158 Monotherapy and its Combination with Pembrolizumab | 4.1 Potential Risks of INCB001158 Monotherapy and its Combination with Pembrolizumab The potential risks of INCB001158, pembrolizumab and the combination of INCB001158 with pembrolizumab are outlined in detail in Section 12.1 of the protocol. | [] |
NCT02903914 | 4.2 | Potential Benefit of INCB001158 and its Combination with Pembrolizumab | 4.2 Potential Benefit of INCB001158 and its Combination with Pembrolizumab Since INCB001158 is an experimental therapy, it is not known if it will be of benefit to patients. Based on what is known about the expression of Arginase in cancers and the immunosuppressive effect of Arginase, though the depletion of arginine,... | [] |
NCT02903914 | 5.0 | STUDY DESIGN | 5.0 STUDY DESIGN Protocol INCB 01158-101 is a Phase 1 open-label study of the arginase inhibitor INCB001158 given as monotherapy and in combination with the immune checkpoint inhibitor pembrolizumab, an anti-programmed cell death protein-1 (anti-PD-1) agent.  Figure 5.0-1: Study design. | [] |
NCT02903914 | 5.1 | Part 1. Dose Escalation | 5.1 Part 1. Dose Escalation Part 1a of this Phase 1 study will begin with a standard, open-label, 3+3 dose-escalating design of single agent INCB001158 in patients with advanced/metastatic solid tumors. Dose escalation will continue until identification of a maximum tolerated dose (MTD) or to a planned maximum daily do... | [] |
NCT02903914 | 5.1.1 | Dose Escalation Rules and Definition of Maximally Tolerated Dose (MTD) | 5.1.1 Dose Escalation Rules and Definition of Maximally Tolerated Dose (MTD) Dose limiting toxicities (DLTs) observed in the first 28 days of dosing for monotherapy dose escalation (Part 1a) or the first 42 days of dosing for combination dose escalation (Part 1b) will be used to determine escalation to the next dose le... | [] |
NCT02903914 | 5.1.2 | Dose-Limiting Toxicity | 5.1.2 Dose-Limiting Toxicity During dose escalation, patients must receive at least 75% of the planned INCB001158 administrations (Parts 1a and 1b) and two doses of pembrolizumab (Part 1b only) in the DLT evaluation window to be considered evaluable for DLT, unless the patient has a DLT or has the study treatment held ... | [
"Non- Hematologic DLTs:",
"Hematologic DLTs:",
"Rationale for urinary orotic acid threshold"
] |
NCT02903914 | 5.1.3 | Definition of Recommended Phase 2 Dose (RP2D) | 5.1.3 Definition of Recommended Phase 2 Dose (RP2D) The RP2D for INCB001158 both as monotherapy and in combination with pembrolizumab will be selected on the basis of emerging safety, PK and pharmacodynamic data and will not exceed the maximally tolerated dose (MTD). The RP2D will either be the MTD or a lower dose if P... | [] |
NCT02903914 | 5.2 | Part 2. Single Agent Cohort Expansion | 5.2 Part 2. Single Agent Cohort Expansion Following completion of monotherapy Dose Escalation and selection of the RP2D for INCB001158 in Part 1a, the following cohorts of patients will be enrolled to receive single agent INCB001158 at the RP2D. Part 2a: Monotherapy Cohort Expansion in NSCLC patients This expansion coh... | [] |
NCT02903914 | 5.3 | Part 3. Combination Cohort Expansion | 5.3 Part 3. Combination Cohort Expansion Upon selection of the RP2D for INCB001158 in combination with pembrolizumab in Part 1b, cohorts of specific patients will be enrolled to receive INCB001158 in combination with pembrolizumab at the RP2D to further evaluate safety and identify an early signal of clinical activity.... | [
"Part 3c: INCB001158 in combination with pembrolizumab in patients with urothelial cell carcinoma (UCC) that would be unlikely to have an objective response to monotherapy pembrolizumab",
"Part 3e: INCB001158 in combination with pembrolizumab in patients with microsatellite stable (MSS) CRC.",
"Part 3f: INCB001... |
NCT02903914 | 6.0 | SAMPLE SIZE | 6.0 SAMPLE SIZE Approximately 216 patients are planned for recruitment to the monotherapy and combination Dose Escalation cohorts. Approximately 148 patients are planned for recruitment in Stage 1 monotherapy and combination Expansion Cohorts. The number of patients may be increased in Stage 2 in each Expansion Cohort ... | [] |
NCT02903914 | 7.0 | INCLUSION/EXCLUSION CRITERIA | 7.0 INCLUSION/EXCLUSION CRITERIA | [] |
NCT02903914 | 7.1 | Inclusion Criteria | 7.1 Inclusion Criteria - 1. Patients must have a histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy. Additional criteria specific to different Parts/Cohorts of the study are provided below. - 2. Ability to provide written informed consent in accor... | [
"Part 1: Inclusion Criteria Specific to the Dose Escalation",
"Part 1a: Inclusion Criteria Specific to the Monotherapy Dose Escalation",
"Part 1b: Inclusion Criteria Specific to the PD-1 Combination Dose Escalation",
"Part 1c: Inclusion Criteria Specific to the PD-1 Combination Moderately Renally Impaired Coh... |
NCT02903914 | 7.2 | Exclusion Criteria | 7.2 Exclusion Criteria - 1. Any other current or previous malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, c) prostate cancer with stable prostate specific antigen (PSA) levels for 3 years, d) or other neoplasm that, in the ... | [
"Disease-specific Exclusion Criteria:",
"Part 1b AND Part 3",
"Part 3",
"Part 3a: NSCLC"
] |
NCT02903914 | 8.0 | RADIOLOGICAL TUMOR ASSESSMENTS | 8.0 RADIOLOGICAL TUMOR ASSESSMENTS As part of Protocol Amendment 2-US 3, dated 10 NOV 2020, the irRECIST endpoints have been removed. This Section refers to the radiological tumor assessments before Protocol Amendment 2-US 3. All patients will be evaluated for tumor response both according to Response Evaluation Criter... | [
"PROTOCOL DETAILS"
] |
NCT02903914 | 10.0 | BACKGROUND AND RATIONALE | 10.0 BACKGROUND AND RATIONALE | [] |
NCT02903914 | 10.1 | Background | 10.1 Background | [] |
NCT02903914 | 10.1.1 | Immunosuppressive Myeloid Cells and Arginase | 10.1.1 Immunosuppressive Myeloid Cells and Arginase Solid tumors have been shown to have moderate to extensive infiltration of immunosuppressive myeloid cells (Solito 2014). Myeloid Derived Suppressor Cells (MDSCs) and neutrophils are present in multiple solid tumors and correlate with poor outcome (Gentles 2015). Both... | [] |
NCT02903914 | 10.1.2 | Arginase 1 Expression in Cancer Patients | 10.1.2 Arginase 1 Expression in Cancer Patients In cancer patients, arginase in the tumor microenvironment is expressed by myeloid cells which release arginase from intracellular granules into the extracellular milieu following stimulation. Arginase is released from fully differentiated neutrophils/polymorphonuclear ce... | [] |
NCT02903914 | 10.1.3 | Selectivity of INCB001158 | 10.1.3 Selectivity of INCB001158 INCB001158 is a potent, selective, and reversible inhibitor of human recombinant arginase 1 and 2 (IC50's of 100 and 275 nM, respectively). INCB001158 is also able to inhibit the elevated arginase activity present in the plasma of renal cancer patients with a similar potency. To assess ... | [] |
NCT02903914 | 10.1.4 | Activity of INCB001158 in Cell-Based Assays | 10.1.4 Activity of INCB001158 in Cell-Based Assays Activated T-cells and NK-cells require the amino acid arginine to proliferate. Arginine is metabolized in the tumor environment by arginase that has been secreted from MDSCs and neutrophils (Munder 2005). Arginine depletion leads to a suppression of T-cell and NK-cell ... | [] |
NCT02903914 | 10.1.5 | Immunosuppression by Arginase in Mice Versus Humans | 10.1.5 Immunosuppression by Arginase in Mice Versus Humans Arginase is an immunosuppressive enzyme in mice and humans that limits the availability of extracellular arginine to T-cells in the tumor microenvironment. MDSCs participate in the immunosuppressive process in both species; however, the biology of MDSCs is fund... | [] |
NCT02903914 | 10.1.6 | Pharmacodynamics of INCB001158 in Tumors and Tissues in Mice | 10.1.6 Pharmacodynamics of INCB001158 in Tumors and Tissues in Mice The tumor distribution and pharmacodynamic effects of INCB001158 were evaluated in mice bearing subcutaneously-implanted murine Lewis Lung Carcinoma (LLC) tumors 2 hr after treatment with a single dose or 2 hr after the last of five doses administered ... | [] |
NCT02903914 | 10.1.7 | Efficacy of INCB001158 in Tumor-Bearing Syngeneic Mice | 10.1.7 Efficacy of INCB001158 in Tumor-Bearing Syngeneic Mice Oral BID administration of single agent INCB001158 produced a dose-dependent reduction in the growth of subcutaneously implanted LLC tumors with significant activity at doses as low as 10 mg/kg (Figure 10.1-4[A]). A dose-related systemic increase in the plas... | [] |
NCT02903914 | 10.1.8 | Nonclinical Toxicity Testing of INCB001158 | 10.1.8 Nonclinical Toxicity Testing of INCB001158 INCB001158 is well tolerated in all species at doses that produce robust pharmacodynamic effects. There is a substantial safety margin of ≥ 16-fold from the projected clinical efficacious exposure (AUC and Cmax) to the exposures that were well tolerated in the GLP toxic... | [] |
NCT02903914 | 10.1.9 | Previous Human Experience | 10.1.9 Previous Human Experience As of 23 May 2018, the Phase 1 clinical trial INCB 01158-101, previously referred to as CX-1158-101, is enrolling solid tumor patients to receive INCB001158 on a BID schedule as single agent and in combination with pembrolizumab. The recommended phase 2 dose (RP2D) for single agent INCB... | [] |
NCT02903914 | 10.1.10 | Pharmacokinetics of INCB001158 | 10.1.10 Pharmacokinetics of INCB001158 Administration of INCB001158 to solid tumor patients resulted in pharmacologically active exposure beginning with the first dose of 50 mg. The first three dose escalation cohorts enrolled patients at doses of 50, 100, and 150 mg BID. The pharmacokinetic data available as of 26 Jun... | [] |
NCT02903914 | 10.1.11 | Pharmacodynamics of INCB001158 | 10.1.11 Pharmacodynamics of INCB001158 The pharmacodynamic activity of INCB001158 was determined by direct measurement of arginine concentration and arginase activity in plasma. Comparing to healthy volunteers, the cancer patients enrolled in this trial had reduced median plasma arginine concentration and elevated leve... | [] |
NCT02903914 | 10.1.12 | Safety of Single Agent INCB001158 | 10.1.12 Safety of Single Agent INCB001158 The preliminary safety profile of INCB001158 has been evaluated during dose escalation from 50 to 150 mg BID. INCB001158 has been well tolerated at all doses tested. The rate of treatment-related adverse events has been low (40% of pts), all of which have been mild to moderate ... | [
"Effects on hepatic urea cycle function"
] |
NCT02903914 | 10.2 | Rationale for Study Design | 10.2 Rationale for Study Design | [] |
NCT02903914 | 10.2.1 | Rationale for Starting Dose | 10.2.1 Rationale for Starting Dose The starting dose for monotherapy dose escalation will be 50 mg BID. This dose was selected based on the results of the GLP-compliant preclinical toxicology studies conducted in rats and cynomolgus monkeys. This dose is approximately one-thirty-sixth (1/36 th ) of the No Observable Ad... | [] |
NCT02903914 | 10.2.2 | Rationale for Dose Escalation Strategy | 10.2.2 Rationale for Dose Escalation Strategy The dose escalation for this study will follow standard Modified Fibonacci dose escalation schedule for both monotherapy and the pembrolizumab combination (see Table 5.1-1). As described in Section 5.1, the selection of this dose escalation schedule was guided by the safety... | [] |
NCT02903914 | 10.2.2.1 | Rationale for Dose in Patients with Moderately Impaired Renal Function | 10.2.2.1 Rationale for Dose in Patients with Moderately Impaired Renal Function A considerable proportion of patients with the tumor types being evaluated in this study have moderately impaired renal function (defined as CrCl 30-49 mL/min) due to multiple factors including underlying disease, prior treatments and proce... | [] |
NCT02903914 | 10.2.3 | Rationale for Patient Populations | 10.2.3 Rationale for Patient Populations | [] |
NCT02903914 | 10.2.3.1 | Monotherapy | 10.2.3.1 Monotherapy This is a Phase 1 study evaluating the safety and tolerability of INCB001158 in cancer patients. Since it unknown whether INCB001158 is efficacious, only patients with metastatic disease or advanced disease that is not amenable to local therapy will be enrolled. Further, only patients for whom ther... | [] |
NCT02903914 | 10.2.3.2 | Combination with Anti-PD-1 (Pembrolizumab) | 10.2.3.2 Combination with Anti-PD-1 (Pembrolizumab) As of the date when this amendment was authored, the anti-PD-1 agent pembrolizumab has been approved for the treatment of metastatic melanoma, NSCLC, SCCHN, urothelial carcinoma, and solid tumors that are microsatellite instability-high (MSI-H) or mismatch repair defi... | [] |
NCT02903914 | 11.0 | PROCEDURES | 11.0 PROCEDURES All patients must sign an IRB/IEC-approved informed consent prior to starting any protocolspecific procedures, including screening procedures. During the consent process, the person obtaining consent must inform the patient of all elements of informed consent. Patients must also meet the inclusion and e... | [] |
NCT02903914 | 11.1 | Screening Period | 11.1 Screening Period | [] |
NCT02903914 | 11.1.1 | Prior Treatment | 11.1.1 Prior Treatment Reasonable efforts will be made during the screening period to determine all prior therapeutic treatments received by the patient. All previous cancer treatments, including systemic therapies, radiation, and/or surgical procedures, should be recorded on the patients' electronic case report forms ... | [] |
NCT02903914 | 11.1.2 | Concomitant Treatment | 11.1.2 Concomitant Treatment Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed during the ongoing trial. If there is a clinical indication for any medication or vaccination specifically prohibited during the trial, discontinuation from trial therapy or vaccination may be requ... | [] |
NCT02903914 | 11.1.2.1 | Acceptable Concomitant Medications | 11.1.2.1 Acceptable Concomitant Medications Concomitant treatment with other therapies is permitted if the medication is not expected to interfere with the evaluation of safety or efficacy of the study treatments. During the study, if the use of any concomitant treatment becomes necessary (e.g., for treatment of an adv... | [] |
NCT02903914 | 11.1.2.2 | Prohibited Concomitant Medications | 11.1.2.2 Prohibited Concomitant Medications Patients are prohibited from receiving the following therapies during the Screening and Treatment Phase (including retreatment for post-complete response relapse) of this trial: - Antineoplastic systemic chemotherapy or biological therapy - Immunotherapy not specified in this... | [] |
NCT02903914 | 11.1.3 | Screening Evaluation | 11.1.3 Screening Evaluation The following screening assessments must be performed within 21 days before study treatment administration on C1D1 according to the Attachment 1 [with the exception of imaging (CT/MRI); scans performed within 28 days of study treatment administration on C1D1 are acceptable]. Procedures liste... | [] |
NCT02903914 | 11.2 | Study Procedures | 11.2 Study Procedures Screening physical exam, urinalysis, serum chemistry, coagulation, and hematology that occurred within 3 days prior to C1D1 do not need to be repeated unless a clinically significant change in the interim is suspected. Patients in Part 1A should be instructed to fast overnight (> 8 hours prior to ... | [] |
NCT02903914 | 11.2.1 | Cycle 1 | 11.2.1 Cycle 1 During Cycle 1, patients will undergo the following procedures: - AE Monitoring - Recording of concomitant medications - Vital signs and weight - Symptom-directed physical exam - ECOG Performance status evaluation - Clinical laboratory evaluation (hematology, coagulation, serum chemistry, ammonia, and ur... | [] |
NCT02903914 | 11.2.1.1 | Part 1a and 1c Only: Cycle 1 Day 1 and Day 15 | 11.2.1.1 Part 1a and 1c Only: Cycle 1 Day 1 and Day 15 Patients in Parts 1a and 1c will have a full pharmacokinetic (PK) and pharmacodynamic evaluation on Cycle 1 Day 1 following a single dose of INCB001158. Dosing on the BID schedule will commence on Cycle 1 Day 2. On Cycle 1 Day 1 and Day 15, patients will arrive at ... | [] |
NCT02903914 | 11.2.2 | Cycle 2 and All Subsequent Cycles | 11.2.2 Cycle 2 and All Subsequent Cycles A detailed breakdown of the visit schedule and sample collection time points for Cycle 2 and subsequent cycles can be found in Attachments 1 and 2. Patients will return to the clinic and undergo the following procedures: - AE monitoring - Recording of concomitant medications - V... | [] |
NCT02903914 | 11.2.2.1 | Part 1a Only: Cycle 2 Days 1-8 | 11.2.2.1 Part 1a Only: Cycle 2 Days 1-8 Patients in Part 1a will participate in a food effect assessment. During Cycle 2 Day 1 through Day 7, patients will be taking their INCB001158 dose with food. Recommendations on meals can be found in the Meal Recommendations section of the Study Reference Manual. On Cycle 2 Day 8... | [] |
NCT02903914 | 11.2.2.2 | Part 2d Only | 11.2.2.2 Part 2d Only  | [] |
NCT02903914 | 11.3 | Other Schedules and Procedures | 11.3 Other Schedules and Procedures For Study Parts 1a and 2, radiographic evaluation of tumor burden (e.g., diagnostic CT/MRI) will occur at Screening and approximately every 8 weeks after study initiation, or more frequently as clinically indicated. For Study Parts 1b and 3, radiographic evaluation of tumor burden (e... | [] |
NCT02903914 | 11.4 | End of Treatment (EOT) | 11.4 End of Treatment (EOT) The End of Treatment (EOT) visit must occur within 28 days of treatment discontinuation and prior to initiation of any new anti-cancer therapy/regimen. All patients discontinuing study treatment for any reason should undergo the following EOT procedures: - AE monitoring - Recording of concom... | [] |
NCT02903914 | 11.5 | Follow-Up | 11.5 Follow-Up | [] |
NCT02903914 | 11.5.1 | Safety Follow-Up | 11.5.1 Safety Follow-Up The safety follow-up period is the interval between the EOT visit and the scheduled follow-up visits, which should occur 30 to 37 days (all patients) and 90 to 97 days (Parts 1b and 3 only) after the final dose of study treatments. Adverse events (all patients) and SAEs (Parts 1a and 2 only) mus... | [] |
NCT02903914 | 11.5.2 | Disease Status Follow-Up | 11.5.2 Disease Status Follow-Up Patients who discontinue study treatment for reasons other than disease progression will continue to be assessed for their disease status during the follow-up phase and should continue to have tumor assessments every 8 weeks (monotherapy) or 9 weeks (pembrolizumab combination) until a ne... | [] |
NCT02903914 | 11.6 | Screen Failures | 11.6 Screen Failures Patients who sign an informed consent form, are not assigned to a treatment, and do not receive either INCB001158 or pembrolizumab are defined as screen failures. For all screen failures, the Investigator will enter the screening number, patient initials, and reason(s) for screen failure into the e... | [] |
NCT02903914 | 11.7 | Safety Evaluation | 11.7 Safety Evaluation Routine safety and tolerability will be evaluated from the results of reported signs and symptoms, scheduled physical examinations, vital sign measurements, duplicate 12-lead ECGs (including QTcF intervals), and clinical laboratory test results. More frequent safety evaluations may be performed i... | [] |
NCT02903914 | 11.7.1 | Physical Examination | 11.7.1 Physical Examination Complete physical examinations will be performed by a licensed physician (or physician's assistant or nurse practitioner) at Screening and End of Treatment. Symptom-directed physical exam are required as clinically indicated. Please refer to the Schedule of Study Assessments (Attachment 1). | [] |
NCT02903914 | 11.7.2 | Vital Signs | 11.7.2 Vital Signs Vital signs (blood pressure, respiratory rate, pulse rate, and temperature) will be obtained in the sitting position. All patients should be sitting for 3-5 min prior to obtaining vital signs. Orthostatic vital signs will be measured on Cycle 1 days 1 and 15 at predose and 4 hrs post dose during the ... | [] |
NCT02903914 | 11.7.3 | Electrocardiograms | 11.7.3 Electrocardiograms Patients should rest in the supine position for at least 5 min before each 12-lead ECG recording is started. Duplicate ECG recordings must be performed using a standard, high-quality, highfidelity electrocardiograph machine equipped with computer-based interval measurements. The average of val... | [] |
NCT02903914 | 11.7.4 | Safety Laboratory Determinations | 11.7.4 Safety Laboratory Determinations Laboratory evaluations will be performed as noted in the Schedule of Study Assessment (Attachment 1A and 1B).     | [] |
NCT02903914 | 11.9 | Pharmacokinetic Evaluation | 11.9 Pharmacokinetic Evaluation | [] |
NCT02903914 | 11.9.1 | Blood Collection | 11.9.1 Blood Collection Plasma PK samples will be used to measure concentrations of INCB001158. Blood samples for PK analysis should be collected at the requested time (Attachment 2). The exact actual time of collection must be noted in the source documents and eCRFs. | [] |
NCT02903914 | 11.9.2 | Intensive PK Sampling | 11.9.2 Intensive PK Sampling Patients enrolled in Parts 1a and 1c will participate in the intensive PK sampling schedule. Plasma PK samples will be collected on Cycle 1, Days 1 and 15 at pre-dose and post-dose at 0.5, 1, 2, 4, 6, 8, and 12 hr. In addition, patients assigned to the intensive PK group in Part 1a only wil... | [] |
NCT02903914 | 11.9.3 | Sparse PK Sampling | 11.9.3 Sparse PK Sampling Patients that are not part of the intensive PK group will have PK samples collected on Cycle 1 Days 1 and 15, and on Day 1 of Cycles 2, 3, and 4. Refer to the PK Sampling Schedule (Attachment 2) for time points and blood volumes to be collected. | [] |
NCT02903914 | 11.9.5 | Bioanalytical Methodology | 11.9.5 Bioanalytical Methodology The plasma samples will be analyzed for INCB001158 by using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method of appropriate specificity and sensitivity according to Good Laboratory Practices (GLPs). PK samples taken on Cycle 1 Day 1 in Part 1a will be analyze... | [] |
NCT02903914 | 12.0 | POTENTIAL TOXICITIES, DOSE MODIFICATION AND MANAGEMENT OF TOXICITIES | 12.0 POTENTIAL TOXICITIES, DOSE MODIFICATION AND MANAGEMENT OF TOXICITIES | [] |
NCT02903914 | 12.1 | Potential Toxicities | 12.1 Potential Toxicities | [] |
NCT02903914 | 12.1.1 | INCB001158 | 12.1.1 INCB001158 INCB001158 is a potent and selective inhibitor of arginase 1 and arginase 2. Arginase 1 is primarily expressed in granulocytic myeloid cell granules, where it is excreted extracellularly and depletes extracellular arginine levels, and in liver hepatocytes, where it functions intracellularly as part of... | [
"Potential Urea Cycle Toxicity",
"Immune-related AEs (irAEs)",
"Alterations in hemodynamic status"
] |
NCT02903914 | 12.1.2 | Pembrolizumab (Patients Enrolled in Parts 1b, 1c, and 3) | 12.1.2 Pembrolizumab (Patients Enrolled in Parts 1b, 1c, and 3) Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programm... | [] |
NCT02903914 | 12.1.2.1 | INCB001158 + Pembrolizumab Combination | 12.1.2.1 INCB001158 + Pembrolizumab Combination The safety and tolerability of INCB001158 + pembrolizumab is not known. A primary objective of the current study is to evaluate the safety and tolerability of the combination of pembrolizumab and INCB001158. Preclinical studies of the combination of an anti-PD-1 agent and... | [] |
NCT02903914 | 12.1.3 | Dose Modifications and Toxicity Management | 12.1.3 Dose Modifications and Toxicity Management The expected toxicity risks for INCB001158 based on preclinical toxicity study data are summarized above. In general, management of AEs related to INCB001158 includes withholding the medication for moderate to severe toxicities and providing the appropriate supportive c... | [] |
NCT02903914 | 12.1.3.1 | Dose Modification Guidelines | 12.1.3.1 Dose Modification Guidelines Patients will be monitored continuously for AEs while on study. Treatment modifications (e.g., dose delay) will be based on specific laboratory and AE criteria. INCB001158: Guidelines for AE management and dose modifications of INCB001158 due to AEs are provided in Table 12.1-1. Th... | [] |
NCT02903914 | 12.1.3.2 | Resumption of Study Treatment | 12.1.3.2 Resumption of Study Treatment For both INCB001158 and pembrolizumab, treatment may be delayed for up to 4 weeks from the last dose. Delays longer than 4 weeks are allowed only in cases where a prolonged steroid taper is required to manage drug-related AEs or, in some cases, if the delay was due to a non-drug-r... | [
"General instructions"
] |
NCT02903914 | 12.1.3.3 | Supportive Care Guidelines | 12.1.3.3 Supportive Care Guidelines Patients should receive appropriate supportive care measures as deemed necessary by the treating Investigator. Guidelines outlined below should be used in conjunction with information provided in the pembrolizumab product label: Hyperammonemia: Patients should be monitored for elevat... | [] |
NCT02903914 | 12.2 | Dose Adjustments, Infusion Delays, and Missed Doses | 12.2 Dose Adjustments, Infusion Delays, and Missed Doses Missed doses of INCB001158 should be skipped. If a patient forgets to take a dose of INCB001158 study drug and he/she is outside of the allotted window period (± 6 hr), he/she should be instructed to skip that dose and NOT to take extra INCB001158 study drug at t... | [] |
NCT02903914 | 12.3 | Discontinuation of Treatment and Withdrawal of Patients | 12.3 Discontinuation of Treatment and Withdrawal of Patients The reasons a patient may discontinue or be withdrawn from the study include, but are not limited to, adverse events, disease progression, patient request, Investigator decision, protocol violation, patient noncompliance, and study termination by the Sponsor.... | [] |
NCT02903914 | 13.0 | STUDY DRUG AND OTHER STUDY TREATMENTS | 13.0 STUDY DRUG AND OTHER STUDY TREATMENTS Study treatment is defined as any investigational treatment(s) or marketed product(s) intended to be administered to a study subject according to the study Protocol. There are 2 investigational study treatments in this study – INCB001158 and pembrolizumab. INCB001158 is also r... | [] |
NCT02903914 | 13.1 | Study Treatment Administration | 13.1 Study Treatment Administration
INCB001158 Study drug (INCB001158) needs to be taken orally as capsule or tablet (25 mg or 100 mg per capsule or tablet) formulation. INCB001158 will be administered only to patients who have signed and dated an Informed Consent Form. Patients in Part 1a and 2: INCB001158 needs to b... | [
"INCB001158",
"Pembrolizumab"
] |
NCT02903914 | 13.2 | Packaging and Labeling | 13.2 Packaging and Labeling INCB001158 capsules and tablets (25 and 100 mg) are manufactured, packaged, and labeled according to current Good Manufacturing Practices (cGMP). All product labels will be in the local language and will comply with the legal requirements of each country. For additional information, please r... | [] |
NCT02903914 | 13.3 | Storage and Stability | 13.3 Storage and Stability
INCB001158 INCB001158 capsules and tablets will be stored at the clinical site, as indicated on the study drug label, i.e., room temperature, between 15ºC - 30ºC (59ºF - 86ºF). Patients will be requested to store the study drug at the recommended storage conditions noted on the label, out of... | [
"INCB001158",
"Pembrolizumab"
] |
NCT02903914 | 13.4 | INCB001158 Accountability, Reconciliation, and Return | 13.4 INCB001158 Accountability, Reconciliation, and Return On Day 1 of Cycle 1, patients will be provided with enough INCB001158 to last until their next clinic visit. For patients in Parts 1a and 2, patients will return on Day 1 of each cycle thereafter and will receive a 28-day supply of INCB001158; the number of cap... | [] |
NCT02903914 | 13.5 | Study Treatment Compliance | 13.5 Study Treatment Compliance Compliance with all study-related treatments should be emphasized to the patient by the site personnel, and appropriate steps should be taken to optimize compliance during the study. Compliance with INCB001158 will be calculated by the sponsor based on the drug accountability documented ... | [] |
NCT02903914 | 14.0 | MEASURES TO MINIMIZE/AVOID BIAS | 14.0 MEASURES TO MINIMIZE/AVOID BIAS Each patient will be assigned a unique number and will keep this number for the duration of the study. Patient numbers will not be reassigned or reused for any reason. Patients should be identified to the Sponsor only by their assigned number, initials (not required for EU), date of... | [] |
NCT02903914 | 15.0 | STATISTICAL ANALYSIS | 15.0 STATISTICAL ANALYSIS | [] |
NCT02903914 | 15.1 | General Statistical Considerations | 15.1 General Statistical Considerations Protocol INCB 01158-101 is a Phase 1 multicenter, open-label study in patients with advanced and metastatic solid tumors. Since this is an open-label clinical trial, descriptive statistics will be employed to analyze the data by tumor type and dose level. Summary statistics for c... | [] |
NCT02903914 | 15.2 | Sample Size and Power | 15.2 Sample Size and Power Dose Escalation: The goal is to determine a dose level of INCB001158 for which the rate of DLTs is less than 33%. Up to approximately 108 patients are planned for single agent dose escalation (Part 1a) and 108 patients for combination dose escalation (Part 1b), both including backfill patient... | [] |
NCT02903914 | 15.3 | Analysis Populations | 15.3 Analysis Populations | [] |
NCT02903914 | 15.3.1 | Safety Population | 15.3.1 Safety Population All patients who receive at least 1 dose of INCB001158 or pembrolizumab will be included in the analysis of safety, regardless of the duration of treatment. AE and laboratory data from all patients in the safety population will be evaluated for safety. Patients from dose escalation will be comb... | [] |
NCT02903914 | 15.3.2 | DLT-Evaluable Populations in Dose Escalation | 15.3.2 DLT-Evaluable Populations in Dose Escalation DLTs will be evaluated during dose escalation. Unless doses are missed in Cycle 1 due to drugrelated AE(s), a patient must receive at least 75% of the planned INCB001158 doses (43 of 56 total doses) to be considered evaluable for DLT. If a patient received less than 4... | [] |
NCT02903914 | 15.3.3 | Efficacy Evaluable Populations | 15.3.3 Efficacy Evaluable Populations The Response Evaluable Population includes all patients who received at least 1 dose of study treatment (INCB001158 or pembrolizumab), completed a baseline scan, and met at least 1 of the following criteria: • The patient had at least 1 post-baseline scan. • The patient discontinue... | [] |
NCT02903914 | 15.4 | Efficacy Analysis | 15.4 Efficacy Analysis Response to treatment will be evaluated using RECIST v1.1 for patients with solid tumors (except for mesothelioma; Eisenhauer 2009). For patients with pleural mesothelioma, response will be evaluated using the modified RECIST criteria for pleural mesothelioma (Byrne 2004, Attachment 5). Responses... | [] |
NCT02903914 | 15.5 | Safety Analysis | 15.5 Safety Analysis Safety variables to be analyzed by dose level and tumor type are AEs, laboratory test results (hematology, coagulation, serum chemistry, and urinalysis), ECG, weight, and vital signs. Adverse event terms recorded on the eCRFs will be mapped to preferred terms using the most recent version of the Me... | [] |
NCT02903914 | 15.6 | Pharmacokinetic Analysis | 15.6 Pharmacokinetic Analysis For Part 1a- Dose Escalation PK samples, a noncompartmental method of analysis will be used to analyze the plasma concentrations of INCB001158. The maximum plasma concentration (Cmax) and the time to attain the Cmax (Tmax) will be determined directly from the observed data. In Part 1a, ful... | [] |
NCT02903914 | 15.7 | Precautions | 15.7 Precautions Although major adverse events are not anticipated, the Investigator must proceed with utmost caution. Equipment, supplies, and properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected reaction. Patients must be selected carefully and closely monit... | [] |
NCT02903914 | 16.0 | SAFETY MONITORING AND REPORTING | 16.0 SAFETY MONITORING AND REPORTING | [] |
NCT02903914 | 16.1 | Adverse Events | 16.1 Adverse Events | [] |
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