Metastatic Solid TumorPhase 1NCT05474859
Subjects With Advanced or Metastatic Solid Tumor Malignancies
A Phase 1 study testing XT-0528 in people with Metastatic Solid Tumor and Advanced Solid Tumor, run by Xenthera, Inc..
Trial summary
This study is an open-label, Phase 1, multicenter, continuous dose escalation study of XT-0528 in adult subjects with Advanced or Metastatic Solid Tumor Malignancies. The study will consist of 4 periods: Screening Period (up to 28 days prior to Cycle 1 Day 1) Safety Run-in Period (Cycle 1; continuous dosing on Days… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Solid Tumor, Advanced Solid Tumor
- What is being tested?
- XT-0528
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Dec 2024to Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Subject must be ≥18 years of age at the time of consent;
- Able to understand the key components of the study as described in the written informed consent document, and willing and able to provide written informed consent;
- In the opinion of the Investigator, is able to adhere to the requirements of the study;
- Willing and able to comply with the contraceptive requirements of the study:
- If female, is premenarcheal, surgically sterile (post hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), postmenopausal (>12 months of amenorrhea without alternative medical causes), or, if of childbearing potential, is using a highly effective method of contraception (combined estrogen/progestogen or progestogen-only hormonal contraceptives associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion/ligation, vasectomized partner[s], double barrier method [male condom with either cap, diaphragm or sponge with spermicide], or true abstinence of heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject [periodic abstinence , eg, calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal, are not acceptable methods of contraception]), and agrees to continued use of this method until 120 days after the EOS Visit.
- If male, is vasectomized and has received medical assessment of surgical success, has undergone bilateral orchidectomy, or agrees to use an approved method of contraception (true abstinence of heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject, double barrier method [male condom with either cap, diaphragm or sponge with spermicide], female partner's use of a highly effective method of contraception, female partner is postmenopausal, or female partner is surgically sterile) and agrees to use this method until 120 days after the End of Study (EOS) Visit.
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- Subject must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and have no additional approved standard of care treatment options, in the opinion of the Investigator;
- Subject must have at least one biopsy accessible tumor;
- Subject must have at least one radiographically measurable lesion as per RECIST v1.1 defined as a lesion that is ≥10 mm in longest diameter or lymph node that is ≥15 mm in short axis as imaged by computed tomography (CT) scan or magnetic resonance imaging (MRI);
- Subject must be willing to undergo screening and on-study tumor biopsy. Note: if archival tissue from the identified tumor is available from a previous clinical biopsy (within the past year), a screening biopsy will not be required;
- Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2;
- Subject must have an anticipated life expectancy >3 months;
- Subject must have normal organ and bone marrow function within 14 days of initiating study drug as defined below:
- Absolute neutrophil count ≥1,500/mcL;
- Platelets ≥100,000/mcL;
- Total bilirubin <1.5 × ULN (except known Gilbert's syndrome);
- Aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase SGOT)]/ Alanine aminotransferase (ALT) [serum glutamic-pyruvic transaminase (SGPT)] ≤2.5 × upper limit of normal (ULN);
- Creatinine clearance ≥60 mL/min/1.73 m2 calculated using the Cockcroft-Gault (C-G) equation.
- Subjects must have resolution (Grade ≤1 or returned to baseline) of toxic effect(s) of the most recent prior therapy except:
- Grade 2 alopecia and Grade 2 fatigue, for which resolution is not required;
- Grade 2 elevation of AST, ALT or total bilirubin for patients with liver metastasis who started treatment with Grade 2 AST/ALT/total bilirubin and the highest increase was <50% relative to baseline and lasted for less than 1 week.
- Subjects who received major surgery or radiation therapy of >30 Gy, must have recovered from the toxicity and/or complications from the intervention.
Who cannot join
- Received other recent antitumor therapy including:
- Investigational therapy administered within the 28 days or 5 half-lives, whichever is shorter, prior to the first scheduled day of dosing in this study;
- Radiation or other standard systemic therapy within 14 days prior to the first scheduled dose in this study, including, in addition (if necessary), the timeframe for resolution of any actual or anticipated toxicities from such radiation.
- Subject is expected to require any other form of antineoplastic therapy while on study;
- Subject with active autoimmune disease requiring disease modifying therapy;
- Subject has known history of prior malignancy except subjects who have undergone potentially curative therapy with no evidence of that disease recurrence within 5 years of therapy initiation. Allowable active malignancies include basal cell carcinoma, squamous cell (skin) carcinoma, or indolent lymphoma/leukemia not requiring treatment.
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- Subject requiring concurrent systemic corticosteroid therapy >10 mg/day of prednisone;
- Subject with known active hepatitis B/C infection (positive viral titers) that has not been treated;
- Subjects with known uncontrolled Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) on anti-retroviral therapy defined by a cluster of differentiation 4 (CD4) count <200;
- Subject has known central nervous system, meningeal, or epidural disease. Subjects with stable brain metastases for at least 4 weeks following definitive local treatment without new or enlarging brain metastases are eligible if corticosteroid requirement is ≤7.5 mg/day of prednisone (or equivalent);
- Subject with a known history of significant cardiovascular disease as evidence by New York Heart Association (NYHA) classification Stage III/IV heart failure, unstable angina, myocardial infarction within the past 6 months, or uncontrolled arrhythmias;
- Subjects has known history of corrected QT Interval (QTc) prolongation or observed QTc prolongation >470 ms during screening ECG;
- Subject with known history of gastrointestinal (GI) disease that could affect drug absorption (eg, malabsorptive disorders, inflammatory bowel disease, short bowel from significant bowel resection, intestinal obstruction for peritoneal carcinomatosis);
- Subject with known history or presence of allergic or adverse response to XT-0528 or related drugs or its excipients;
- Subject requires use of strong inhibitors, strong inducers, and sensitive substrates of major cytochrome P450 enzymes (CYP) and drug transporters.
- Subjects requiring chronic use of acid reducing agents (ARAs) are excluded from the study unless able to suspend use of ARAs for 48 hours prior to PK sampling days
- Subject is pregnant, plans to become pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of study participation;
- Subject has known psychiatric or substance abuse disorder(s) that would interfere with cooperation with required elements of study participation.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase 1, Multicenter Tolerability and Pharmacokinetic Study of Ascending Continuous Oral Doses of XT-0528 in Subjects With Advanced or Metastatic Solid Tumor Malignancies
This study is an open-label, Phase 1, multicenter, continuous dose escalation study of XT-0528 in adult subjects with Advanced or Metastatic Solid Tumor Malignancies.
The study will consist of 4 periods:
Screening Period (up to 28 days prior to Cycle 1 Day 1) Safety Run-in Period (Cycle 1; continuous dosing on Days 1-21 of 28-day cycle) Continuous Dosing Period (Cycle 2 and beyond; continuous dosing on Days 1-28 of 28-day cycle) Safety Follow-up Period (30 days post-last dose).
Read the detailed description
Primary Objective
- To determine the dose recommended for future Phase 2 studies (RP2D) that maximally suppresses T helper 17 (TH17) cell activities with an absence of dose limiting toxicity (DLT) and without exceeding the maximum tolerable dose (MTD).
Secondary Objective
- To establish the pharmacokinetics (PK) of orally administered XT-0528.
- To observe subjects for evidence of the antitumor activity of XT-0528.
- Conditions
- Metastatic Solid Tumor, Advanced Solid Tumor
- Being tested
- XT-0528
- Keywords
- Interleukin 17 (IL17), retinoic acid related orphan nuclear receptor γt (RORyt), T Helper Cell (TH17)
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XT-0528Drug
Once Daily
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | XT-0528 250 mg administered once daily Receives: Drug: XT-0528 |
| Cohort 2 | Experimental | XT-0528 500 mg administered once daily Receives: Drug: XT-0528 |
| Cohort 3 | Experimental | XT-0528 1000 mg administered once daily Receives: Drug: XT-0528 |
| Cohort 4 | Experimental | XT-0528 1500 mg administered once daily Receives: Drug: XT-0528 |
| Cohort 5 | Experimental | XT-0528 2500 mg administered once daily Receives: Drug: XT-0528 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the dose recommended for future Phase 2 studies (RP2D) that maximally suppresses Th17 cell activities
Determination of Th17 cell suppression by measuring serum levels of Th17 cytokines before and during continuous dosing of XT-0528
Measured: Cycle 1 (Days 1-21)
To determine the dose recommended for future Phase 2 studies (RP2D) with an absence of dose limiting toxicity (DLT) and without exceeding the maximum tolerable dose (MTD).
Determination of MTD, in the continuous dosing setting, as assessed by collection of adverse event/serious adverse event (AE/SAE) information, if MTD is reached during dose escalation.
Measured: Cycle 1 (Days 1-21)
Secondary outcomes (10)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Cmax
maximum plasma concentration (Cmax)
Measured: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Cmax Steady State
maximum plasma concentration at steady state (Cmax,ss)
Measured: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Tmax
time to Cmax (Tmax)
Measured: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Tmax Steady State
time to Cmax at Steady State (Tmax,ss)
Measured: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - AUC
area under the concentration-time curve calculated using linear trapezoidal rule from time zero to 24 hours, the dosing interval, after first dose (AUC0-t)
Measured: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - AUC Steady State
area under the concentration-time curve calculated using linear trapezoidal rule from time zero to 24 hours, the dosing interval, after first dose at Steady State (AUC0-tau)
Measured: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To observe subjects for evidence of the antitumor activity of XT-0528 - ORR
To determine the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. * Overall response rate (ORR) is defined as the proportion of participants whose best observed response is either a complete response (CR) or partial response (PR) per RECIST in the population of interest
Measured: End of Cycle 3 (Each cycle is 28 days)
To observe subjects for evidence of the antitumor activity of XT-0528 - PFS
To determine the median progression-free survival (PFS). Progression free survival (PFS) for a participant is defined as the time from first dosing date to the date of the first objectively documented disease progression per RECIST in the population of interest, or death due to any cause, whichever occurs first
Measured: End of Cycle 3 (Each cycle is 28 days)
To measure anti-drug antibody (ADA) formation against XT-0528
Neutralizing antibody assessments will be performed in samples positive for ADA and will be analyzed to determine impact on rate and severity treatment-emergent adverse event(s) (TEAE).
Measured: End of Cycle 3 (Each cycle is 28 days)
To observe subjects for evidence of the antitumor activity of XT-0528 - OS
To determine the median overall survival (OS). Overall survival (OS) is defined as the time from enrollment to the date of death from any cause.
Measured: End of Cycle 3 (Each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2022
- Study startDec 2024 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Solid TumorStudies 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- 3+3 design
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xenthera, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lynne Kelley, MD, Study director, Xenthera, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05474859
- Sponsor's protocol ID
- XT-001
- Status last verified
- Oct 2023
- First submitted
- 18 Jul 2022
- Last updated
- 31 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There are no plans to share information at this time.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter Tolerability and Pharmacokinetic Study of Ascending Continuous Oral Doses of XT-0528 in Subjects With Advanced or Metastatic Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT05474859
- Acronym / sponsor ID
- XT-001
- Conditions
- Metastatic Solid Tumor, Advanced Solid Tumor
- Keywords
- Interleukin 17 (IL17), retinoic acid related orphan nuclear receptor γt (RORyt), T Helper Cell (TH17)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Xenthera, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2024 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 26 Jul 2022 (actual)
- 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.
This study is an open-label, Phase 1, multicenter, continuous dose escalation study of XT-0528 in adult subjects with Advanced or Metastatic Solid Tumor Malignancies.
The study will consist of 4 periods:
Screening Period (up to 28 days prior to Cycle 1 Day 1) Safety Run-in Period (Cycle 1; continuous dosing on Days 1-21 of 28-day cycle) Continuous Dosing Period (Cycle 2 and beyond; continuous dosing on Days 1-28 of 28-day cycle) Safety Follow-up Period (30 days post-last dose).
Detailed description
Primary Objective
- To determine the dose recommended for future Phase 2 studies (RP2D) that maximally suppresses T helper 17 (TH17) cell activities with an absence of dose limiting toxicity (DLT) and without exceeding the maximum tolerable dose (MTD).
Secondary Objective
- To establish the pharmacokinetics (PK) of orally administered XT-0528.
- To observe subjects for evidence of the antitumor activity of XT-0528.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- 3+3 design
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: XT-0528XT-0528 250 mg administered once daily |
| Cohort 2 | Experimental | Drug: XT-0528XT-0528 500 mg administered once daily |
| Cohort 3 | Experimental | Drug: XT-0528XT-0528 1000 mg administered once daily |
| Cohort 4 | Experimental | Drug: XT-0528XT-0528 1500 mg administered once daily |
| Cohort 5 | Experimental | Drug: XT-0528XT-0528 2500 mg administered once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Subject must be ≥18 years of age at the time of consent;
- Able to understand the key components of the study as described in the written informed consent document, and willing and able to provide written informed consent;
- In the opinion of the Investigator, is able to adhere to the requirements of the study;
- Willing and able to comply with the contraceptive requirements of the study:
- Subject must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and have no additional approved standard of care treatment options, in the opinion of the Investigator;
Key exclusion criteria (18 listed)
- Received other recent antitumor therapy including:
- Subject is expected to require any other form of antineoplastic therapy while on study;
- Subject with active autoimmune disease requiring disease modifying therapy;
- Subject has known history of prior malignancy except subjects who have undergone potentially curative therapy with no evidence of that disease recurrence within 5 years of therapy initiation. Allowable active malignancies include basal cell carcinoma, squamous cell (skin) carcinoma, or indolent lymphoma/leukemia not requiring treatment.
- Subject requiring concurrent systemic corticosteroid therapy >10 mg/day of prednisone;
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 |
|---|---|---|
| XT-0528Once Daily | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
To determine the dose recommended for future Phase 2 studies (RP2D) that maximally suppresses Th17 cell activities
Time frame: Cycle 1 (Days 1-21)
Determination of Th17 cell suppression by measuring serum levels of Th17 cytokines before and during continuous dosing of XT-0528
To determine the dose recommended for future Phase 2 studies (RP2D) with an absence of dose limiting toxicity (DLT) and without exceeding the maximum tolerable dose (MTD).
Time frame: Cycle 1 (Days 1-21)
Determination of MTD, in the continuous dosing setting, as assessed by collection of adverse event/serious adverse event (AE/SAE) information, if MTD is reached during dose escalation.
10 secondary outcomes
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Cmax
Time frame: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Cmax Steady State
Time frame: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Tmax
Time frame: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Tmax Steady State
Time frame: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - AUC
Time frame: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - AUC Steady State
Time frame: End of Cycle 1 (Days 1-21 of 28-day Cycle)
To observe subjects for evidence of the antitumor activity of XT-0528 - ORR
Time frame: End of Cycle 3 (Each cycle is 28 days)
To observe subjects for evidence of the antitumor activity of XT-0528 - PFS
Time frame: End of Cycle 3 (Each cycle is 28 days)
To measure anti-drug antibody (ADA) formation against XT-0528
Time frame: End of Cycle 3 (Each cycle is 28 days)
To observe subjects for evidence of the antitumor activity of XT-0528 - OS
Time frame: End of Cycle 3 (Each cycle is 28 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2024.
- Individual participant dataSharing planned: No. There are no plans to share information at this time.
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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.
Lynne Kelley, MD study director
Xenthera, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XT-0528 in people with Metastatic Solid Tumor and Advanced Solid Tumor, run by Xenthera, Inc..
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 22 inclusion and 18 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: opening soon, as of the sponsor's last update on 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sherry L Plantholt, BS (859-462-4625, splantholt@xenthera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the dose recommended for future Phase 2 studies (RP2D) that maximally suppresses Th17 cell activities (time frame: Cycle 1 (Days 1-21)). 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?
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 31 Jul 2024.