Addition of X4P-001 to Nivolumab Treatment in Participants With Renal Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if the combination of X4P-001 plus nivolumab is safe and tolerable. Secondly, the study will investigate if adding X4P-001 to nivolumab treatment has an effect on the body and the cancer tumor, in participants receiving nivolumab but not exhibiting a radiological response.

Official Title
-----------------
A Phase 1B/2A Trial Adding X4P-001 in Patients Receiving Nivolumab for Treatment of Advanced Clear Cell Renal Cell Carcinoma

Conditions
-----------------
Clear Cell Renal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: X4P-001
* Drug: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of Renal Cell Carcinoma with a documented clear cell component (ccRCC). Currently receiving nivolumab and considered by Investigator to have the potential to derive clinical benefit from continuing treatment with nivolumab. Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria on current nivolumab treatment (prior to initiation of this study), has a best response of confirmed stable disease (SD) or confirmed progressive disease (PD). Confirmed SD or confirmed PD refers to a response that is confirmed by a second scan which is at least 4 weeks apart from the previous scan. At least one extra-renal measurable target lesion meeting the criteria of RECIST Version 1.1. Agree to use contraception from screening, through the study, and for at least 5 months after the last dose of nivolumab as follows: for women of childbearing potential agree to use highly-effective contraceptive methods; for males, agree to use a condom with sexual partner. Exclusion Criteria: Pregnant or nursing. Life expectancy of less than 3 months. Performance status greater than or equal to (≥) 2 (Eastern Cooperative Oncology Group [ECOG] criteria). New York Heart Association (NYHA) Class III or IV, uncontrolled hypertension, or clinically significant arrhythmia. Previously received X4P-001. Has a second malignancy. Except: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type. Has active central nervous system (CNS) metastases (including evidence of cerebral edema by Magnetic Resonance Imaging [MRI], or progression from prior imaging study, or any requirement for steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28 days of study treatment. Ongoing clinical adverse events National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade greater than (>) 2 resulting from prior cancer therapies. Known history of Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS); or positive test for hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg). History of clinically significant or uncontrolled cardiac, hepatic, or pulmonary disease. Has had within the past 6 months the occurrence of one or more of the following events: myocardial infarction, cerebrovascular accident, deep vein thrombosis, pulmonary embolism, hemorrhage (NCI CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for Child-Pugh Class B or C), or organ transplantation. Inadequate hematologic, hepatic, or renal function.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: X4P-001 Plus Nivolumab<br>Participants will receive X4P-001 400 milligrams (mg) (as 4 capsules of 100 mg each) orally once daily in combination with nivolumab 240 mg intravenous (IV) infusion (over 60 minutes) every 2 weeks. Study medication will be administered in 28-day cycles and will continue until treatment-limiting toxicity or disease progression. | Drug: X4P-001<br>* X4P-001 will be administered as per the dose and schedule specified in the arm.<br>Drug: Nivolumab<br>* Nivolumab will be administered as per the dose and schedule specified in the arm.<br>* Other names: Opdivo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Drug-related TEAEs: TEAEs with possible, probable, definite, or missing relationship to study medication (X4P-001 or Nivolumab). Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as events occurring on or after the first dose of study drug through 30 days after the last dose. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality, is located in Reported AE section. | From administration of first dose of study medication (Day 1) up to 30 days after last dose (up to 16 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of X4P-001 | Samples were to be analyzed for X4P-001 concentration using reversed-phase high performance liquid chromatography (RP-HPLC) with tandem mass spectrometry (MS) detection. | Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1 | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of X4P-001 | Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection. | Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1 | 
| Minimum Plasma Concentration (Cmin) of X4P-001 | Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection. | Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1 | 
| Time to Reach Cmax (Tmax) of X4P-001 | Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection. | Predose (-30 minutes) on Day 1 of Cycle 1; predose (-10 minutes) on Days 8, 15, and 22 of Cycle 1, and Day 1 of Cycle 3; postdose at 60 and 90 minutes, and 2, 3 4, and 8 hours on Day 22 of Cycle 1 | 
| Objective Response Rate (ORR): Percentage of Participants With Objective Response, Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | ORR was defined as percentage of participants with best overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to less than (<) 10 millimeters (mm). PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months) | 
| Duration of Objective Response (DOR), Evaluated Using RECIST Version 1.1 | DOR was defined as the time from first CR or PR whichever comes first until the time of disease progression by RECIST v1.1 or death due to any cause. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of 1 or more new lesions was also considered progression. | Time from first CR or PR until the time of disease progression or death due to any cause (up to 15 months) | 
| Time to Objective Response, Evaluated Using RECIST Version 1.1 | Time to objective response was defined as time from first administration of combination regimen to first CR or PR whichever comes first. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From administration of first dose of study medication (Day 1) until first appearance of CR or PR (up to 15 months) | 
| Disease Control Rate: Percentage of Participants With CR or PR or Stable Disease (SD), Evaluated Using RECIST Version 1.1 | Disease control rate was defined as percentage of participants with best overall response of CR or PR or SD. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) with a reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. The appearance of 1 or more new lesions was also considered progression. | From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months) | 
| Progression Free Survival (PFS), Evaluated Using RECIST Version 1.1 | PFS was defined as the time from first administration of study medication until objective tumor progression or death from any cause. Tumor progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. An unequivocal progression of existing non-target lesions or the appearance of 1 or more new lesions was also considered progression. | From administration of first dose of study medication (Day 1) until disease progression or death from any cause (up to 15 months) | 
| Time to Progression (TTP), Evaluated Using RECIST Version 1.1 | TTP was defined as the time from first administration of study medication until objective tumor progression. Tumor progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions or the appearance of 1 or more new lesions was also considered progression. | From administration of first dose of study medication (Day 1) until disease progression (up to 15 months) |