Subjects With Advanced or Metastatic Solid Tumor Malignancies

NCT05474859 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: XT-001
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief 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 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).

Conditions

Metastatic Solid Tumor; Advanced Solid Tumor

Keywords

Interleukin 17 (IL17); retinoic acid related orphan nuclear receptor γt (RORyt); T Helper Cell (TH17)

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Cycle 1 (Days 1-21)

Secondary Outcomes (10)

• To establish the pharmacokinetics (PK) of orally administered XT-0528 and its (R)-isomer - Cmax

  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

  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

  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

  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

  End of Cycle 1 (Days 1-21 of 28-day Cycle)

Study Arms (5)

Cohort 1

EXPERIMENTAL

XT-0528 250 mg administered once daily

Drug: XT-0528

Cohort 2

EXPERIMENTAL

XT-0528 500 mg administered once daily

Drug: XT-0528

Cohort 3

EXPERIMENTAL

XT-0528 1000 mg administered once daily

Drug: XT-0528

Cohort 4

EXPERIMENTAL

XT-0528 1500 mg administered once daily

Drug: XT-0528

Cohort 5

EXPERIMENTAL

XT-0528 2500 mg administered once daily

Drug: XT-0528

Interventions

XT-0528 DRUG

Once Daily

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

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

You may qualify if:

• 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.
• 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;

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Xenthera, Inc.: lead

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lynne Kelley, MD

  Xenthera, Inc.

  STUDY DIRECTOR

Central Study Contacts

Sherry L Plantholt, BS

CONTACT

859-462-4625; splantholt@xenthera.com

Lynne Kelley, MD

CONTACT

617-272-5909; lkelley@xenthera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 design

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 26, 2022
• Study Start: December 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 31, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share