Clear Cell Renal Cell Carcinoma
Conditions
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.
Interventions
DRUGX4P-001
X4P-001 will be administered as per the dose and schedule specified in the arm.
DRUGNivolumab
Nivolumab will be administered as per the dose and schedule specified in the arm.
Sponsors
X4 Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From administration of first dose of study medication (Day 1) up to 30 days after last dose (up to 16 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) of X4P-001 | 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 | Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection. |
| Minimum Plasma Concentration (Cmin) of X4P-001 | 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 | Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection. |
| Time to Reach Cmax (Tmax) of X4P-001 | 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 | Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection. |
| Objective Response Rate (ORR): Percentage of Participants With Objective Response, Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months) | 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. |
| Maximum Observed Plasma Concentration (Cmax) of X4P-001 | 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 | Samples were to be analyzed for X4P-001 concentration using reversed-phase high performance liquid chromatography (RP-HPLC) with tandem mass spectrometry (MS) detection. |
| Time to Objective Response, Evaluated Using RECIST Version 1.1 | From administration of first dose of study medication (Day 1) until first appearance of CR or PR (up to 15 months) | 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. |
| Disease Control Rate: Percentage of Participants With CR or PR or Stable Disease (SD), Evaluated Using RECIST Version 1.1 | From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months) | 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. |
| Progression Free Survival (PFS), Evaluated Using RECIST Version 1.1 | From administration of first dose of study medication (Day 1) until disease progression or death from any cause (up to 15 months) | 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. |
| Time to Progression (TTP), Evaluated Using RECIST Version 1.1 | From administration of first dose of study medication (Day 1) until disease progression (up to 15 months) | 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. |
| Duration of Objective Response (DOR), Evaluated Using RECIST Version 1.1 | Time from first CR or PR until the time of disease progression or death due to any cause (up to 15 months) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| X4P-001 Plus Nivolumab Participants received X4P-001 400 mg (as 4 capsules of 100 mg each) orally once daily in combination with nivolumab 240 mg IV infusion (over 60 minutes) every 2 weeks. Study medication was administered in 28-day cycles and continued until treatment-limiting toxicity or disease progression. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Clinical Deterioration | 1 |
| Overall Study | Disease Progression | 3 |
| Overall Study | Study Termination | 1 |
Baseline characteristics
| Characteristic | X4P-001 Plus Nivolumab |
|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 8.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 2 / 9 |
Outcome results
Primary
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.
Time frame: From administration of first dose of study medication (Day 1) up to 30 days after last dose (up to 16 months)
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| X4P-001 Plus Nivolumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 9 Participants |
| X4P-001 Plus Nivolumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 2 Participants |
| X4P-001 Plus Nivolumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | X4P-001-Related TEAEs | 9 Participants |
| X4P-001 Plus Nivolumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Nivolumab-Related TEAEs | 9 Participants |
Secondary
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.
Time frame: 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
Population: The study was terminated and the PK samples collected could not be analyzed due to insufficient data available to assess the outcome measure as per the prespecified method of analysis.
Secondary
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.
Time frame: From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months)
Population: ITT population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| X4P-001 Plus Nivolumab | Disease Control Rate: Percentage of Participants With CR or PR or Stable Disease (SD), Evaluated Using RECIST Version 1.1 | 88.9 percentage of participants |
Secondary
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 frame: Time from first CR or PR until the time of disease progression or death due to any cause (up to 15 months)
Population: ITT population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| X4P-001 Plus Nivolumab | Duration of Objective Response (DOR), Evaluated Using RECIST Version 1.1 | NA months |
Secondary
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.
Time frame: 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
Population: The study was terminated and the pharmacokinetic (PK) samples collected could not be analyzed due to insufficient data available to assess the outcome measure as per the prespecified method of analysis.
Secondary
Minimum Plasma Concentration (Cmin) of X4P-001
Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.
Time frame: 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
Population: The study was terminated and the PK samples collected could not be analyzed due to insufficient data available to assess the outcome measure as per the prespecified method of analysis.
Secondary
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.
Time frame: From administration of first dose of study medication (Day 1) until disease progression, study completion or early termination (up to 15 months)
Population: Intent-to-treat (ITT) population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| X4P-001 Plus Nivolumab | Objective Response Rate (ORR): Percentage of Participants With Objective Response, Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 11.1 percentage of participants |
Secondary
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.
Time frame: From administration of first dose of study medication (Day 1) until disease progression or death from any cause (up to 15 months)
Population: ITT population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| X4P-001 Plus Nivolumab | Progression Free Survival (PFS), Evaluated Using RECIST Version 1.1 | NA months |
Secondary
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.
Time frame: From administration of first dose of study medication (Day 1) until first appearance of CR or PR (up to 15 months)
Population: ITT population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| X4P-001 Plus Nivolumab | Time to Objective Response, Evaluated Using RECIST Version 1.1 | NA months |
Secondary
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.
Time frame: From administration of first dose of study medication (Day 1) until disease progression (up to 15 months)
Population: ITT population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| X4P-001 Plus Nivolumab | Time to Progression (TTP), Evaluated Using RECIST Version 1.1 | NA months |
Secondary
Time to Reach Cmax (Tmax) of X4P-001
Samples were to be analyzed for X4P-001 concentration using RP-HPLC with tandem MS detection.
Time frame: 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
Population: The study was terminated and the PK samples collected could not be analyzed due to insufficient data available to as per the prespecified method of analysis.