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

NCT02923531 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: X4P-001-RCCB
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

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.

Conditions

Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

• 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

• 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

• 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

• 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)

Study Arms (1)

X4P-001 Plus Nivolumab

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

X4P-001 DRUG

X4P-001 will be administered as per the dose and schedule specified in the arm.

X4P-001 Plus Nivolumab

Nivolumab DRUG

Nivolumab will be administered as per the dose and schedule specified in the arm.

Also known as: Opdivo

X4P-001 Plus Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• X4 Pharmaceuticals: lead

Study Sites (4)

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Hackensack, New Jersey, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Related Publications (1)

• Choueiri TK, Atkins MB, Rose TL, Alter RS, Ju Y, Niland K, Wang Y, Arbeit R, Parasuraman S, Gan L, McDermott DF. A phase 1b trial of the CXCR4 inhibitor mavorixafor and nivolumab in advanced renal cell carcinoma patients with no prior response to nivolumab monotherapy. Invest New Drugs. 2021 Aug;39(4):1019-1027. doi: 10.1007/s10637-020-01058-2. Epub 2021 Jan 28.

  PMID: 33507454 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

mavorixafor; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Due to low enrollment, the study was terminated early. Data for some pre-registered endpoints were therefore not collected or analysed and could not be reported.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: X4 Pharmacueticals

patientinfo@x4pharma.com

(857) 529-8300

Study Officials

• Chief Medical Officer

  X4 Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2016
• First Posted: October 4, 2016
• Study Start: December 7, 2016
• Primary Completion: August 8, 2018
• Study Completion: August 8, 2018
• Last Updated: December 29, 2022
• Results First Posted: December 29, 2022

Record last verified: 2022-11

Locations

US (4)