Trial Outcomes & Findings for Trial of X4P-001 in Participants With Advanced Renal Cell Carcinoma (NCT NCT02667886)

Last Updated: 2024-10-03

Results Overview

An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. Adverse events with onset after administration of the first dose of study drug up to 10 days after last dosing date were considered TEAEs. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

74 participants

Primary outcome timeframe

From first dose of study drug up to 10 days after last dosing (maximum exposure: 52.1 months)

Results posted on

2024-10-03

Participant Flow

This study comprised 3 parts: Part A (Phase 1: Dose escalation cohorts), Part B (Phase 2: Dose expansion cohort), and Part C (Dose escalation and expansion cohort). As planned, the efficacy and safety data collected per dose level not per study part.

Participant milestones

Participant milestones
Measure	Dose Escalation (Part A): X4P-001 200 mg BID With Axitinib Participants received X4P-001 200 milligrams (mg) orally twice daily (BID) with axitinib at 5 mg orally BID.	Dose Escalation (Part A): X4P-001 400 mg QD With Axitinib Participants received X4P-001 400 mg orally once daily (QD) with axitinib at 5 mg orally BID.	Dose Escalation (Part A): X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID.	Dose Expansion (Part B): X4P-001 400 mg QD With Axitinib Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID.	Dose Escalation and Expansion (Part C): X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD.
Dose Escalation (Part A) STARTED	3	7	6	0	0
Dose Escalation (Part A) Received at Least 1 Dose of Study Drug	3	7	6	0	0
Dose Escalation (Part A) COMPLETED	1	0	0	0	0
Dose Escalation (Part A) NOT COMPLETED	2	7	6	0	0
Dose Expansion (Part B) STARTED	0	0	0	55	0
Dose Expansion (Part B) Received at Least 1 Dose of Study Drug	0	0	0	55	0
Dose Expansion (Part B) COMPLETED	0	0	0	1	0
Dose Expansion (Part B) NOT COMPLETED	0	0	0	54	0
Dose Escalation and Expansion (Part C) STARTED	0	0	0	0	3
Dose Escalation and Expansion (Part C) Received at Least 1 Dose of Study Drug	0	0	0	0	3
Dose Escalation and Expansion (Part C) COMPLETED	0	0	0	0	0
Dose Escalation and Expansion (Part C) NOT COMPLETED	0	0	0	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation (Part A): X4P-001 200 mg BID With Axitinib Participants received X4P-001 200 milligrams (mg) orally twice daily (BID) with axitinib at 5 mg orally BID.	Dose Escalation (Part A): X4P-001 400 mg QD With Axitinib Participants received X4P-001 400 mg orally once daily (QD) with axitinib at 5 mg orally BID.	Dose Escalation (Part A): X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID.	Dose Expansion (Part B): X4P-001 400 mg QD With Axitinib Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID.	Dose Escalation and Expansion (Part C): X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD.
Dose Escalation (Part A) Adverse Event	1	3	1	0	0
Dose Escalation (Part A) Disease Progression	1	4	3	0	0
Dose Escalation (Part A) Dose-limiting toxicity (DLT)	0	0	2	0	0
Dose Expansion (Part B) Adverse Event	0	0	0	9	0
Dose Expansion (Part B) Clinical Deterioration	0	0	0	3	0
Dose Expansion (Part B) Disease Progression	0	0	0	38	0
Dose Expansion (Part B) Withdrawal by Subject	0	0	0	4	0
Dose Escalation and Expansion (Part C) Adverse Event	0	0	0	0	1
Dose Escalation and Expansion (Part C) DLT	0	0	0	0	2

Baseline Characteristics

Trial of X4P-001 in Participants With Advanced Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=62 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib n=6 Participants Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy n=3 Participants Participants received X4P-001 600 mg orally QD in Part C.	Total n=74 Participants Total of all reporting groups
Age, Customized 16-64 Years	3 Participants n=5 Participants	37 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	45 Participants n=21 Participants
Age, Customized ≥65 Years	0 Participants n=5 Participants	25 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	29 Participants n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	52 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	62 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	7 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	55 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	67 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	17 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	17 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	40 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	52 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to 10 days after last dosing (maximum exposure: 52.1 months)

Population: Safety population included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=62 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib n=6 Participants Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy n=3 Participants Participants received X4P-001 600 mg orally QD in Part C.
Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	3 Participants	62 Participants	6 Participants	3 Participants

SECONDARY outcome

Timeframe: From administration of first dose of study medication until disease progression, study completion or early termination (up to 80 weeks)

Population: Clinically evaluable population included all participants who received at least 1 dose of study medication, who had at least 1 valid post-baseline response (CR/PR/stable disease \[SD\]/progressive disease \[PD\]) and had no major protocol deviations which impacted the efficacy assessment. Due to dose-limiting toxicities (DLTs) experienced by participants, the sample size was too small for data to be collected for this Outcome Measure for the "X4P-001 600 mg QD With Axitinib" arm.

The 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 \<10 millimeters (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=59 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Objective Response Rate (ORR), as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	66.7 percentage of participants Interval 9.4 to 99.2	27.1 percentage of participants Interval 16.4 to 40.3	—	—

SECONDARY outcome

Timeframe: From administration of first dose of study medication until first appearance of CR or PR (up to 80 weeks)

Population: Clinically evaluable population included all participants who received at least 1 dose of study medication, who had at least 1 valid post-baseline response (CR/PR/SD/PD) and had no major protocol deviations which impacted the efficacy assessment. Due to DLTs experienced by participants, the sample size was too small for data to be collected for this Outcome Measure for the "X4P-001 600 mg QD With Axitinib" arm.

Time to objective response was defined as time from first administration of combination regimen to first CR or PR whichever came 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.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=59 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Time to Objective Response, as Assessed Using RECIST v1.1	12.9 months Interval 1.9 to Due to smaller number of participants with an event, upper limit of 95% confidence interval (CI) could not be calculated.	14.6 months Interval 12.9 to Due to smaller number of participants with an event, upper limit of 95% CI could not be calculated.	—	—

SECONDARY outcome

Timeframe: Time from first CR or PR until the time of disease progression or death due to any cause (up to 80 weeks)

Population: Clinically evaluable population included all participants who received at least 1 dose of study medication, who had at least 1 valid post-baseline response (CR/PR/SD/PD) and had no major protocol deviations which impacted efficacy assessment. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Due to DLTs experienced by participants, the sample size was too small for data to be collected for this Outcome Measure for "X4P-001 600 mg QD With Axitinib" arm.

The DOR was defined as the time from first CR or PR whichever came first until the time of disease progression or death by 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.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=2 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=16 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Duration of Objective Response (DOR), as Assessed Using RECIST v1.1	NA months Interval 9.2 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.	16.6 months Interval 10.8 to 36.0	—	—

SECONDARY outcome

Timeframe: From administration of first dose of study medication until disease progression, study completion or early termination (up to 80 weeks)

Population: Clinically evaluable population included all participants who received at least 1 dose of study medication, who had at least 1 valid post-baseline response (CR/PR/SD/PD) and had no major protocol deviations which impacted the efficacy assessment. Due to DLTs experienced by participants, the sample size was too small for data to be collected for this Outcome Measure for the "X4P-001 600 mg QD With Axitinib" arm.

The DCR was defined as the percentage of participants with best overall response of CR, PR or stable disease (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.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=59 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Disease Control Rate (DCR), as Assessed Using RECIST v1.1	100.0 percentage of participants Interval 29.2 to 100.0	71.2 percentage of participants Interval 57.9 to 82.2	—	—

SECONDARY outcome

Timeframe: From administration of first dose of study medication until disease progression (up to 80 weeks)

Population: Clinically evaluable population included all participants who received at least 1 dose of study medication, who had at least 1 valid post-baseline response (CR/PR/SD/PD) and had no major protocol deviations which impacted the efficacy assessment. Due to DLTs experienced by participants, the sample size was too small for data to be collected for this Outcome Measure for the "X4P-001 600 mg QD With Axitinib" arm.

The TTP was defined as the time from first administration of combination regimen until PD. 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 or the appearance of 1 or more new lesions was also considered progression.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=59 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Time to Progression (TTP), as Assessed Using RECIST v1.1	11.1 months Interval 5.5 to Due to smaller number of participants with an event, upper limit of 95% CI could not be calculated.	7.4 months Interval 5.6 to 14.7	—	—

SECONDARY outcome

Timeframe: From administration of first dose of study medication until disease progression or death from any cause (up to 80 weeks)

Population: Clinically evaluable population included all participants who received at least 1 dose of study medication, who had at least 1 valid post-baseline response (CR/PR/SD/PD) and had no major protocol deviations which impacted the efficacy assessment. Due to DLTs experienced by participants, the sample size was too small for data to be collected for this Outcome Measure for the "X4P-001 600 mg QD With Axitinib" arm.

The PFS was defined as the time from first administration of combination regimen until disease progression or death from any cause. 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. An unequivocal progression of existing non-target lesions or the appearance of 1 or more new lesions was also considered progression.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=59 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Progression Free Survival (PFS), as Assessed Using RECIST v1.1	11.1 months Interval 5.5 to Due to smaller number of participants with an event, the upper limit of 95% CI could not be calculated.	7.4 months Interval 5.5 to 12.5	—	—

SECONDARY outcome

Timeframe: Day 1 and Day 15 of Cycle 1

Population: The pharmacokinetic (PK) population included all participants who had at least one evaluable concentration. Here 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=57 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib n=6 Participants Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Parts A and B: Maximum Plasma Concentration (Cmax) of X4P-001 Day 1	1070 nanograms (ng)/milliliter (mL) Geometric Coefficient of Variation 59.5	3130 nanograms (ng)/milliliter (mL) Geometric Coefficient of Variation 67.2	4170 nanograms (ng)/milliliter (mL) Geometric Coefficient of Variation 42.7	—
Parts A and B: Maximum Plasma Concentration (Cmax) of X4P-001 Day 15	831 nanograms (ng)/milliliter (mL) Geometric Coefficient of Variation 8.20	3710 nanograms (ng)/milliliter (mL) Geometric Coefficient of Variation 73.5	3900 nanograms (ng)/milliliter (mL) Geometric Coefficient of Variation 39.2	—

SECONDARY outcome

Timeframe: Day 1 and Day 15 of Cycle 1

Population: The PK population included all participants who had at least one evaluable concentration. Here 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.

Outcome measures

Outcome measures
Measure	X4P-001 200 mg BID With Axitinib n=3 Participants Participants received X4P-001 200 mg orally BID with axitinib at 5 mg orally BID in Part A.	X4P-001 400 mg QD With Axitinib n=57 Participants Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID in either Part A or Part B.	X4P-001 600 mg QD With Axitinib n=6 Participants Participants received X4P-001 600 mg orally QD with axitinib at 5 mg orally BID in Part A.	X4P-001 600 mg QD Monotherapy Participants received X4P-001 600 mg orally QD in Part C.
Area Under the Curve From Time 0 to the Last Quantifiable Timepoint (AUC0-tlast) Day 1	2200 hours*ng/mL Geometric Coefficient of Variation 62.8	6790 hours*ng/mL Geometric Coefficient of Variation 80.2	9830 hours*ng/mL Geometric Coefficient of Variation 54.3	—
Area Under the Curve From Time 0 to the Last Quantifiable Timepoint (AUC0-tlast) Day 15	3000 hours*ng/mL Geometric Coefficient of Variation 26.4	13100 hours*ng/mL Geometric Coefficient of Variation 90.7	15100 hours*ng/mL Geometric Coefficient of Variation 44.3	—

Adverse Events

X4P-001 200 mg BID With Axitinib

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

X4P-001 400 mg QD With Axitinib

Serious events: 26 serious events

Other events: 62 other events

Deaths: 2 deaths

X4P-001 600 mg QD With Axitinib

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

X4P-001 600 mg QD Monotherapy

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

X4 Pharmaceuticals

Phone: (857) 529-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60