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

• ClinicalTrials.gov Identifier: NCT02923531
• Recruitment Status: Completed
• First Posted: October 4, 2016
• Last Update Posted: August 1, 2019
• Sponsor: X4 Pharmaceuticals
• Information provided by (Responsible Party): X4 Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Clear Cell Renal Cell Carcinoma	Drug: X4P-001; Drug: Nivolumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1B/2A Trial Adding X4P-001 in Patients Receiving Nivolumab for Treatment of Advanced Clear Cell Renal Cell Carcinoma
• Actual Study Start Date: December 7, 2016
• Actual Primary Completion Date: August 8, 2018
• Actual Study Completion Date: August 8, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: X4P-001 Plus Nivolumab; 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 treatment will be administered in 28-day cycles and will continue until treatment-limiting toxicity or disease progression.	Drug: X4P-001; X4P-001 will be administered as per the dose and schedule specified in the arm.; Drug: Nivolumab; Nivolumab will be administered as per the dose and schedule specified in the arm.; Other Name: Opdivo

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 15 months, from time of enrollment through disease progression, study completion or early termination ]

Secondary Outcome Measures :

1. Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 8 hrs post-dose ]
2. Area Under the Curve (AUC) [ Time Frame: Up to 8 hrs post-dose ]
3. Minimum Plasma Concentration (Cmin) [ Time Frame: Up to 8 weeks ]
4. Objective Response Rate [ Time Frame: Up to 15 months, from time of enrollment through disease progression, study completion or early termination ]
5. Duration of Objective Response [ Time Frame: Up to 15 months, from time of enrollment through disease progression, study completion or early termination ]
6. Time to Objective Response [ Time Frame: Up to 15 months, from time of enrollment through disease progression, study completion or early termination ]
7. Disease Control Rate [ Time Frame: 16 weeks and 24 weeks ]
8. Progression Free Survival [ Time Frame: Up to 15 months, from time of enrollment through disease progression, study completion or early termination ]
9. Time to Progression [ Time Frame: Up to 15 months, from time of enrollment through disease progression, study completion or early termination ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 RECIST v1.1 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.

Contacts and Locations

Locations

United States, District of Columbia

Washington, District of Columbia, United States

United States, Massachusetts

Boston, Massachusetts, United States

United States, New Jersey

Hackensack, New Jersey, United States

United States, North Carolina

Chapel Hill, North Carolina, United States

Sponsors and Collaborators

X4 Pharmaceuticals

Investigators

• Study Director: Chief Medical Officer; X4 Pharmaceuticals, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: X4 Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02923531
• Other Study ID Numbers: X4P-001-RCCB
• First Posted: October 4, 2016
• Last Update Posted: August 1, 2019
• Last Verified: July 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action