MelanomaPhase 1X4P-001-MELANCT02823405
X4P-001 and Pembrolizumab in Patients With Advanced Melanoma
A Phase 1 study testing X4P-001 and Pembrolizumab in people with Melanoma, run by X4 Pharmaceuticals at 4 sites in United States.
Trial summary
The goals of this protocol are 1) to investigate the safety and tolerability of X4P-001 in combination with Keytruda® (pembrolizumab) in patients with advanced melanoma, and 2) to assess serial biopsies of melanoma tumor lesions obtained throughout the study for inflammatory and tumor cell infiltrates. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- X4P-001 and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 4 sitesUnited States
- Study dates
- 15 Sep 2016to 15 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for this study, a patient must meet all of the following inclusion criteria:
- Be at least 18 years of age.
- Has signed the current approved informed consent form.
- Has a histologically confirmed diagnosis of malignant melanoma.
- Has at least two separate cutaneous lesions suitable for punch biopsies (at least 3 mm diameter).
- For women of childbearing potential and men, agree to use a highly effective method of contraceptive from screening, through the study, and for at least 4 weeks after the last dose of study drug.
- For women of childbearing potential, must have a negative pregnancy test (serum or urine) on Day 1 prior to initiating study treatment, and are not nursing.
- Be willing and able to comply with the schedule, treatment, and biopsies specified by this protocol.
Who cannot join
- Patients with any of the following will be excluded from participation in the study:
- Has performance status Grade 2 or higher (Eastern Cooperative Oncology Group [ECOG] criteria).
- Has ongoing acute clinical adverse events NCI CTCAE Grade 2 or greater resulting from prior cancer therapies (except alopecia).
- Has had within the past 6 months the occurrence or persistence of one or more of the following medical conditions that could not be controlled with usual medical care (e.g., required emergency care or hospitalization): angina, congestive heart failure, diabetes, seizure disorder.
- Has had within the past 6 months the occurrence of one or more of the following events: myocardial infarction, cerebrovascular accident, hemorrhage (CTC Grade 3 or 4), chronic liver disease (meeting criteria for Child-Pugh Class B or C), a second active malignancy requiring ongoing treatment during the trial, organ transplantation.
- Has had within the 4 weeks prior to initiation of study drug, or is expected to have during the study period, surgery requiring general anesthesia
Show all 24Show fewer
- Has, at screening, serologic laboratory tests meeting one or more of the following criteria:
- An indeterminate or positive test for antibody to human immunodeficiency virus (HIV-1 or -2).
- An indeterminate or positive test for antibody to hepatitis C virus (HCV), unless documented to have no detectable viral load on two independent samples.
- A positive test for hepatitis B surface antigen (HBsAg).
- Has, at screening, safety laboratory tests meeting one or more of the following criteria:
- Hemoglobin <9.0 g/dL
- Absolute neutrophil count (ANC) <1,500/μL
- Platelets <100,000/μL
- Creatinine >2.0x ULN
- Serum aspartate transaminase (AST) >3x ULN
- Serum alanine transaminase (ALT) >3x ULN
- Total bilirubin >1.5x ULN (unless due to Gilbert's Syndrome)
- International normalized ratio (INR) >1.5x ULN (unless on therapeutic anti-coagulation).
- Has been previously treated with approved or investigational immunotherapy including oncolytic viruses, or agents directed at CTLA-4, PD-1, or PD-L1 ("checkpoint inhibitors").
- Has previously received other anti-cancer therapy within 2 weeks prior to Day 1, including radiation therapy or chemotherapy. For investigational anti-cancer therapies, the interval will be determined in consultation with the Medical Monitor.
- Has, within 2 weeks prior to Day 1, been regularly taking a medication prohibited based on CYP3A4 interaction.
- Has, at the planned initiation of study drug, an uncontrolled infection.
- Has any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical trial.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Clinical Site
Atlanta, Georgia, 30322
Clinical Site
Houston, Texas, 77030
Clinical Site
Iowa City, Iowa, 52242
Clinical Site
Salt Lake City, Utah, 84112
About this study
Official title: A Phase 1b Trial of X4P-001 Alone and With Pembrolizumab in Patients With Advanced Melanoma
The goals of this protocol are 1) to investigate the safety and tolerability of X4P-001 in combination with Keytruda® (pembrolizumab) in patients with advanced melanoma, and 2) to assess serial biopsies of melanoma tumor lesions obtained throughout the study for inflammatory and tumor cell infiltrates. After completion of study treatment, participants with resectable disease will undergo surgery, unresectable participants may continue on pembrolizumab as standard of care.
Read the detailed description
X4P-001 is an orally bioavailable CXCR4 antagonist that has demonstrated activity in various tumor models. CXCR4 (C-X-C chemokine receptor type 4) is the receptor for CXCL12 (C-X-C chemokine ligand type 12). CXCL12 has potent chemotactic activity for lymphocytes and MDSCs (myeloid-derived suppressor cells), and is important in homing of hematopoietic stem cells to the bone marrow. CXCR4 is also expressed and active on multiple types of human cancers, including melanoma, ccRCC, and ovarian cancer. Additionally, increased expression of CXCR4 on tumor cells has been associated with significantly decreased overall participant survival.
In animal cancer models, interference with CXCR4 function has been demonstrated to disrupt the tumor microenvironment (TME) and unmask the tumor to immune attack by multiple mechanisms, including:
- Decreasing the infiltration of MDSCs
- Increasing the ratio of CD8+ T cells to Treg cells
- Eliminating tumor re-vascularization
Pembrolizumab is a humanized IgG4 kappa monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Pembrolizumab is currently approved for the treatment of unresectable or metastatic melanoma. Analysis of tumor samples before and during treatment in an earlier study demonstrated that a clinical response was associated with an increase in the density of CD8+ T cells in the tumor parenchyma (center), while disease progression was associated with persistent low levels of those cells. In an autochthonous murine model of pancreatic adenocarcinoma, persistent tumor growth despite administration of anti-PD-L1 was similarly associated with failure of tumor-specific cytotoxic T cells to enter the TME despite their presence in the peripheral circulation. This immunosuppressed phenotype was associated with CXCL12 production by cancer-associated fibroblasts. Moreover, administration of a CXCR4 antagonist (AMD3100) induced rapid T-cell accumulation among the cancer cells and, in combination with anti-PD-L1, synergistically decreased tumor growth.
Based on these observations, the hypothesis is that effective CXCR4 antagonism by X4P-001 would be of potential benefit in participants with advanced melanoma and other cancers by multiple mechanisms, resulting in increased anti-tumor immune attack.
- Conditions
- Melanoma
- Being tested
- X4P-001, Pembrolizumab
- Keywords
- Advance malignancy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
X4P-001Drug
Also called AMD11070
X4P-001 100 mg capsules, administered orally, continuous daily dosing
PembrolizumabDrug
Also called Keytruda
Pembrolizumab 2 mg/kg, administered by IV infusion every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| X4P-001 + Pembrolizumab | Experimental | X4P-001 alone, then adding pembrolizumab Receives: Drug: X4P-001; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Measured: Up to 13 weeks, from time of enrollment through study completion or early termination.
Histology Characterization in Sequential Biopsies of Melanoma Lesions
Measured: Up to 13 weeks, from time of enrollment through study completion or early termination.
Secondary outcomes (3)
Blood Biomarker Changes
Measured: Up to 17 weeks, from time of screening through study completion or early termination.
Minimum Plasma Concentration (Cmin)
Measured: Up to 9 weeks, from time of enrollment through end of treatment.
Clinical Tumor Response
Measured: Up to 17 weeks, from time of screening through study completion or early termination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2016 (estimated)
- Study start15 Sep 2016
- Primary completion15 Mar 2018
- Study completion15 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- X4 Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lu Gan, MD, PhD, Study director, X4 Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02823405
- Sponsor's protocol ID
- X4P-001-MELA
- Acronym
- X4P-001-MELA
- Status last verified
- Jul 2020
- First submitted
- 1 Jul 2016
- Last updated
- 7 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Andtbacka RHI, Wang Y, Pierce RH, Campbell JS, Yushak M, Milhem M, Ross M, Niland K, Arbeit RD, Parasuraman S, Bickley K, Yeung CC, Aicher LD, Smythe KS, Gan L. Mavorixafor, an Orally Bioavailable CXCR4 Antagonist, Increases Immune Cell Infiltration and Inflammatory Status of Tumor Microenvironment in Patients with Melanoma. Cancer Res Commun. 2022 Aug 31;2(8):904-913. doi: 10.1158/2767-9764.CRC-22-0090. eCollection 2022 Aug.
PubMed 36923305
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Trial of X4P-001 Alone and With Pembrolizumab in Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT02823405
- Acronym / sponsor ID
- X4P-001-MELA / X4P-001-MELA
- Conditions
- Melanoma
- Keywords
- Advance malignancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- X4 PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2016 (actual)
- Primary completion
- 15 Mar 2018 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 6 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goals of this protocol are 1) to investigate the safety and tolerability of X4P-001 in combination with Keytruda® (pembrolizumab) in patients with advanced melanoma, and 2) to assess serial biopsies of melanoma tumor lesions obtained throughout the study for inflammatory and tumor cell infiltrates. After completion of study treatment, participants with resectable disease will undergo surgery, unresectable participants may continue on pembrolizumab as standard of care.
Detailed description
X4P-001 is an orally bioavailable CXCR4 antagonist that has demonstrated activity in various tumor models. CXCR4 (C-X-C chemokine receptor type 4) is the receptor for CXCL12 (C-X-C chemokine ligand type 12). CXCL12 has potent chemotactic activity for lymphocytes and MDSCs (myeloid-derived suppressor cells), and is important in homing of hematopoietic stem cells to the bone marrow. CXCR4 is also expressed and active on multiple types of human cancers, including melanoma, ccRCC, and ovarian cancer. Additionally, increased expression of CXCR4 on tumor cells has been associated with significantly decreased overall participant survival.
In animal cancer models, interference with CXCR4 function has been demonstrated to disrupt the tumor microenvironment (TME) and unmask the tumor to immune attack by multiple mechanisms, including:
- Decreasing the infiltration of MDSCs
- Increasing the ratio of CD8+ T cells to Treg cells
- Eliminating tumor re-vascularization
Pembrolizumab is a humanized IgG4 kappa monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Pembrolizumab is currently approved for the treatment of unresectable or metastatic melanoma. Analysis of tumor samples before and during treatment in an earlier study demonstrated that a clinical response was associated with an increase in the density of CD8+ T cells in the tumor parenchyma (center), while disease progression was associated with persistent low levels of those cells. In an autochthonous murine model of pancreatic adenocarcinoma, persistent tumor growth despite administration of anti-PD-L1 was similarly associated with failure of tumor-specific cytotoxic T cells to enter the TME despite their presence in the peripheral circulation. This immunosuppressed phenotype was associated with CXCL12 production by cancer-associated fibroblasts. Moreover, administration of a CXCR4 antagonist (AMD3100) induced rapid T-cell accumulation among the cancer cells and, in combination with anti-PD-L1, synergistically decreased tumor growth.
Based on these observations, the hypothesis is that effective CXCR4 antagonism by X4P-001 would be of potential benefit in participants with advanced melanoma and other cancers by multiple mechanisms, resulting in increased anti-tumor immune attack.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| X4P-001 + Pembrolizumab | Experimental | Drug: X4P-001, Drug: PembrolizumabX4P-001 alone, then adding pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- To be eligible for this study, a patient must meet all of the following inclusion criteria:
- Be at least 18 years of age.
- Has signed the current approved informed consent form.
- Has a histologically confirmed diagnosis of malignant melanoma.
- Has at least two separate cutaneous lesions suitable for punch biopsies (at least 3 mm diameter).
Key exclusion criteria (24 listed)
- Has performance status Grade 2 or higher (Eastern Cooperative Oncology Group [ECOG] criteria).
- Has ongoing acute clinical adverse events NCI CTCAE Grade 2 or greater resulting from prior cancer therapies (except alopecia).
- Has had within the past 6 months the occurrence or persistence of one or more of the following medical conditions that could not be controlled with usual medical care (e.g., required emergency care or hospitalization): angina, congestive heart failure, diabetes, seizure disorder.
- Has had within the past 6 months the occurrence of one or more of the following events: myocardial infarction, cerebrovascular accident, hemorrhage (CTC Grade 3 or 4), chronic liver disease (meeting criteria for Child-Pugh Class B or C), a second active malignancy requiring ongoing treatment during the trial, organ transplantation.
- Has had within the 4 weeks prior to initiation of study drug, or is expected to have during the study period, surgery requiring general anesthesia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| X4P-001Also: AMD11070X4P-001 100 mg capsules, administered orally, continuous daily dosing | Drug | X4P-001 + Pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab 2 mg/kg, administered by IV infusion every 3 weeks | Drug | X4P-001 + Pembrolizumab |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: Up to 13 weeks, from time of enrollment through study completion or early termination.
Histology Characterization in Sequential Biopsies of Melanoma Lesions
Time frame: Up to 13 weeks, from time of enrollment through study completion or early termination.
3 secondary outcomes
Blood Biomarker Changes
Time frame: Up to 17 weeks, from time of screening through study completion or early termination.
Minimum Plasma Concentration (Cmin)
Time frame: Up to 9 weeks, from time of enrollment through end of treatment.
Clinical Tumor Response
Time frame: Up to 17 weeks, from time of screening through study completion or early termination.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2020.
- Derived from this study: PubMed 36923305Andtbacka RHI, Wang Y, Pierce RH, Campbell JS, Yushak M, Milhem M, Ross M, Niland K, Arbeit RD, Parasuraman S, Bickley K, Yeung CC, Aicher LD, Smythe KS, Gan L. Mavorixafor, an Orally Bioavailable CXCR4 Antagonist, Increases Immune Cell Infiltration and Inflammatory Status of Tumor Microenvironment in Patients with Melanoma. Cancer Res Commun. 2022 Aug 31;2(8):904-913. doi: 10.1158/2767-9764.CRC-22-0090. eCollection 2022 Aug.
- Individual participant dataSharing planned: No
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lu Gan, MD, PhD study director
X4 Pharmaceuticals, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing X4P-001 and Pembrolizumab in people with Melanoma, run by X4 Pharmaceuticals at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (time frame: Up to 13 weeks, from time of enrollment through study completion or early termination.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02823405, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020; AzTrials last refreshed its copy on 8 Nov 2026.