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Solid Tumor, AdultPhase 1NCT03355066

A Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors

A Phase 1 study testing SM08502 in people with Solid Tumor, Adult, run by Biosplice Therapeutics, Inc. at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is an open-label, multi-center, dose-escalation, dose-finding and expansion study in adult subjects with advanced solid tumors for whom no standard therapy is available. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Adult
What is being tested?
SM08502
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
19 sitesUnited States
Study dates
6 Nov 2017to 14 Nov 2022
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

  • Subjects with advanced solid tumors (as defined below):
  • Part 1A - Subjects with advanced solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit) and for which histologic or cytologic confirmation of malignancy was obtained at diagnosis, with the exception of hepatocellular carcinoma if it meets appropriate imaging-only diagnostic criteria (per the National Comprehensive Cancer Network [NCCN], Liver Imaging Reporting and Data System [LI-RADS], American Association for the Study of Liver Diseases [AASLD], Asian Pacific Association for the Study of the Liver [APASL], or European Association for the Study of the Liver - European Organisation for Research and Treatment of Cancer [EASL-EORTC]).
  • Part 1B - Subjects with advanced and/or metastatic solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit in the Investigator's judgment). Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. The tumor types include: i. NSCLC (adenocarcinoma subtype) ii. TNBC iii. CRPC iv. CRC v. Endometrial cancer (endometrioid subtype) vi. Ovarian cancer (serous, mucinous, and endometrioid subtypes).
  • Part 2 - Subjects with advanced and/or metastatic solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition. Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. Subjects must have received no more than 2 prior lines of myelosuppressive chemotherapy. Additionally, CRPC subjects must have received no more than 4 total lines of treatment (including any hormonal therapies) in any setting. The tumor types include: i. NSCLC (adenocarcinoma subtype) ii. CRPC in two biomarker selected cohorts.
  • Measurable or evaluable disease per RECIST 1.1 (Part 1A). For Parts 1B and 2, at least 1 measurable lesion per RECIST 1.1 that has not been previously irradiated. In CRPC subjects (Parts 1B and 2) without measurable disease per RECIST 1.1, a PSA that is concordant with clinical disease progression (rising) is eligible. A PSA value of 2 ng/ml or greater is required for study entry.
  • Subjects must have archived tumor specimens available for analysis (as specified in Section 7.2.2). Otherwise, a fresh tumor biopsy will be required at study entry. At the discretion of the Sponsor's Medical Monitor, a fresh tumor biopsy may not be required for eligibility if there are extenuating circumstances (e.g., inaccessible sites of disease or lack of subject suitability to undergo a fresh biopsy, or molecular profiling of archived tissue already performed).
  • Subjects must have recovered (i.e., Grade 1 [or better] based on CTCAE v5.0) from all toxicity associated with previous chemotherapy, targeted therapy, experimental therapy, biological therapy, immuno-oncology therapy, surgery, radiotherapy, or other locoregional therapy (Exceptions include subjects with: continuing alopecia regardless of any CTCAE grade, Grade 2 or lower neuropathy, and well-controlled hypothyroidism and/or adrenal insufficiency on chronic hormone replacement. All subjects with these exceptions are eligible).
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

Who cannot join

  • Women who are pregnant or lactating
  • Women of childbearing potential (WOCBP) who do not agree to follow the contraceptive guidelines as outlined in the study protocol
  • Men of reproductive potential who do not agree to follow the contraceptive guidelines as outlined in the study protocol
  • Subjects with a corrected QT interval (QTc) using Fridericia's formula (QTcF) > CTCAE v5.0 Grade 1 (>480 msec) based on the mean of triplicate evaluation at Screening.
  • Subjects with clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), ventricular fibrillation (VF), second or third degree heart block
  • Subjects with myocardial infarction (MI) within 1 year, Class II-IV congestive heart failure (CHF) per New York Heart Association (NYHA) classification, or clinically significant coronary artery disease (CAD)
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  • Subjects with active infection requiring parenteral antibiotic therapy.
  • Organ transplant recipients.
  • Subjects with known osteoporosis.
  • Subjects with a second malignancy unless adequately treated with no recurrence for 3 years. Subjects with history of previous or recent adequately treated skin basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of any source are eligible.
  • Subjects with active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of SM08502 per Investigator's opinion
  • Subjects with known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
  • Subjects with chronic liver disease or dysfunction and a Child-Pugh score of B or C
  • Subjects with untreated, progressing, or known symptomatic brain metastasis
  • Subjects with retinal abnormalities, specifically diabetic retinopathy, macular degeneration, other forms of retinal degenerative disease, or other retinal findings that may place the subject at risk

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Sarah Cannon Research Institute at HealthONE

    Denver, Colorado, 80218

  • City of Hope Medical Center

    Duarte, California, 91010

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • START Midwest

    Grand Rapids, Michigan, 49546

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Medicine Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • UC Davis - Comprehensive Cancer Center

    Sacramento, California, 95817

  • NEXT Oncology

    San Antonio, Texas, 78229

  • UT Health San Antonio - Mays Cancer Center

    San Antonio, Texas, 78229

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Honor Health Research Institute

    Scottsdale, Arizona, 85258

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Arizona Cancer Center

    Tucson, Arizona, 85724

  • START Mountain Region

    West Valley City, Utah, 84119

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Dose-Escalation, Dose-Finding Study Evaluating the Safety and Pharmacokinetics of Orally Administered SM08502 in Subjects With Advanced Solid Tumors

This study is an open-label, multi-center, dose-escalation, dose-finding and expansion study in adult subjects with advanced solid tumors for whom no standard therapy is available. The study will evaluate the safety, tolerability, PK, PD, and preliminary anti-tumor efficacy of SM08502 administered orally, once daily, following a 28-day treatment cycle (Part 1A). Alternative dosing schedules will be explored in Part 1B and the recommended Part 2 dose and schedule will be further evaluated in Part 2.

Subjects will participate in a screening period of up to 14 days. Dosing in 28-day cycles will continue within each subject, unless treatment is discontinued due to toxicity, disease progression, initiation of a new anti-neoplastic therapy, withdrawal of consent, the Sponsor terminates the study, or the subject no longer meets retreatment criteria.

Approximately 10 subjects enrolled in Part 2, irrespective of the tumor type, will be included in a food effect substudy to assess the preliminary effect of a high-fat, high-calorie meal on the PK of SM08502. Subjects participating in the food effect substudy will continue on study and complete assessments as per the Part 2 schedule and receive SM08502 at the recommended Part 2 dose (or another previously assessed dose level and schedule).

Being tested
SM08502
Keywords
SM08502, pan Clk/Dyrk inhibitor, HRR, HRD, LOH High, AR-V7

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SM08502Drug

    SM08502 tablets to be administered orally.

Study groups in NCT03355066
Study groupRoleWhat they receive
Part 1A: Dose EscalationExperimentalCohorts of subjects with advanced solid tumors will receive increasing doses (10, 20, 40, 60, 80, 120, 160, or 200 mg) of SM08502, administered orally, once daily, following 28-day treatment cycles. If the maximum tolerated dose (MTD) is not determined at the 200 mg dose, dosing will continue at 50 mg/dose increments until an MTD is determined. Cohorts will include approximately 1 to 6 subjects according to an accelerated escalation design and safety requirements for expansion of subject numbers. For the purpose of dose escalation and de-escalation, the dose of SM08502 and regimen may be modified based on the type of dose limiting toxicities (DLTs) observed and following data review and discussions between the Sponsor and Investigators.
Receives: Drug: SM08502
Part 1B: Dose FindingExperimentalIndications eligible for Part 1B include castration-resistant prostate cancer (CRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer (CRC), endometrial cancer, or ovarian cancer for which histologic or cytologic confirmation of malignancy was obtained at diagnosis. Initially, two cohorts of 6-24 subjects will be evaluated comparing 2 different doses and schedules of SM08502 (30 mg daily and 40 mg 5 days on and 2 days off), administered orally following 28-day treatment cycles. If appropriate, alternative doses and schedules may be evaluated depending on the results.
Receives: Drug: SM08502
Part 2: ExpansionExperimentalPart 2 will evaluate the recommended Part 2 dose and schedule of SM08502, as determined in Part 1B, in 3 cohorts of subjects. The indications to be evaluated include subjects with advanced and/or metastatic CRPC (two biomarker selection cohorts) and NSCLC for which histologic or cytologic confirmation of malignancy was obtained at diagnosis. Each cohort will enroll up to 20 subjects. Approximately 10 subjects of the total enrolled in Part 2, irrespective of cohort, will be included in a food-effect substudy to assess the preliminary effect of a high-fat, high-calorie meal on the PK of SM08502.
Receives: Drug: SM08502

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1A, Part 1B: Maximum tolerated dose (MTD) of SM08502 based on the frequency and severity of dose-limiting toxicities (DLTs)

    Measured: DLT period of 28 days per dose level

  2. Part 1A, Part 1B and Part 2: Number of participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0

    Measured: Approximately 5 years

  3. Part 1A, Part 1B and Part 2: Change from baseline in blood chemistry parameters: blood urea nitrogen [BUN], creatinine, glucose, potassium, sodium, calcium (micromoles per liter)

    Measured: Approximately 5 years

  4. Part 1A, Part 1B and Part 2: Change from baseline in blood chemistry parameters: aspartate aminotransferase [AST], alanine aminotransferase (ALT), alkaline phosphatase [ALP] (international units per liter)

    Measured: Approximately 5 years

  5. Part 1A, Part 1B and Part 2: Change from baseline in blood chemistry parameters: albumin (grams per day)

    Measured: Approximately 5 years

  6. Part 1A, Part 1B and Part 2: Change from baseline in blood chemistry parameters: chloride, bicarbonate (millimoles per liter)

    Measured: Approximately 5 years

  7. Part 1A, Part 1B and Part 2: Change from baseline in blood chemistry parameter: lactic acid dehydrogenase [LDH] (units per liter)

    Measured: Approximately 5 years

  8. Part 1A, Part 1B and Part 2: Change from baseline in hematology parameter: hemoglobin [Hb] (grams per liter)

    Measured: Approximately 5 years

  9. Part 1A, Part 1B and Part 2: Change from baseline in hematology parameter: hematocrit (proportion of red blood cells in blood)

    Measured: Approximately 5 years

  10. Part 1A, Part 1B and Part 2: Change from baseline in hematology parameter: red blood cells [RBC] count (trillion cells per liter)

    Measured: Approximately 5 years

  11. Part 1A, Part 1B and Part 2: Change from baseline in hematology parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelet count (cells/microliter)

    Measured: Approximately 5 years

  12. Part 1A: Change from baseline in prothrombin time [PT] (seconds)

    Measured: Approximately 5 years

  13. Part 1A: Change from baseline in partial thromboplastin time [PTT] (seconds)

    Measured: Approximately 5 years

  14. Part 1A: Change from baseline in urinalysis parameter: clarity

    Measured: Approximately 5 years

  15. Part 1A: Change from baseline in urinalysis parameter: specific gravity (ratio)

    Measured: Approximately 5 years

  16. Part 1A: Change from baseline in urinalysis parameter: urine pH

    Measured: Approximately 5 years

  17. Part 1A: Change from baseline in urinalysis parameter: protein

    Measured: Approximately 5 years

  18. Part 1A: Change from baseline in urinalysis parameter: glucose (millimole per liter)

    Measured: Approximately 5 years

  19. Part 1A: Change from baseline in urinalysis parameter: ketones (millimoles per liter)

    Measured: Approximately 5 years

  20. Part 1A: Change from baseline in urinalysis parameter: occult blood (10^9 cells per liter)

    Measured: Approximately 5 years

  21. Part 1A: Change from baseline in urinalysis parameter: nitrite

    Measured: Approximately 5 years

  22. Part 1A: Change from baseline in urinalysis parameter: leukocytes (counts per high power field)

    Measured: Approximately 5 years

  23. Part 1A, Part 1B and Part 2: Change from baseline in body temperature (degrees celsius)

    Measured: Approximately 5 years

  24. Part 1A, Part 1B and Part 2: Change from baseline in pulse rate (beats per minute)

    Measured: Approximately 5 years

  25. Part 1A, Part 1B and Part 2: Change from baseline in respiratory rate (breaths per minute)

    Measured: Approximately 5 years

  26. Part 1A, Part 1B and Part 2: Change from baseline in blood pressure (systolic and diastolic) (millimeters of mercury)

    Measured: Approximately 5 years

  27. Part 1A, Part 1B and Part 2: Change from baseline in electrocardiogram (ECG) parameters: PR interval, QRS interval, QT interval, QTcF (milliseconds)

    Measured: Approximately 5 years

  28. Part 1A and Part 1B: Cmax of SM08502 and its metabolite (SM08955) following single dose administration of SM08502

    Measured: Approximately 5 years

  29. Part 1A and Part 1B: tmax of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  30. Part 1A and Part 1B: AUC0-24 of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  31. Part 1A and Part 1B: AUClast of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  32. Part 1A and Part 1B: Cmax,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  33. Part 1A and Part 1B: Cmin,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  34. Part 1A and Part 1B: tmax,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  35. Part 1A and Part 1B: AUC0-24,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  36. Part 2: Tumor response as measured by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) or PCWG3 (Prostate Cancer Working Group 3) criteria where appropriate

    Measured: Approximately 5 years

Secondary outcomes (14)

  1. Part 1A and Part 1B: Tumor response as measured by RECIST 1.1 or PCWG3 criteria where appropriate

    Measured: Approximately 5 years

  2. Part 1A, Part 1B and Part 2: Gene expression profile of RNA isolated from whole blood

    Measured: Approximately 5 years

  3. Part 2: Cmax of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  4. Part 2: tmax of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  5. Part 2: AUC0-24 of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  6. Part 2: AUClast of SM08502 and SM08955 following single dose administration of SM08502

    Measured: Approximately 5 years

  7. Part 2: Cmax,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  8. Part 2: Cmin,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  9. Part 2: tmax,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  10. Part 2: AUC0-24,ss of SM08502 and SM08955 following repeat dose administration of SM08502

    Measured: Approximately 5 years

  11. Part 2: Gene expression and splicing alterations in post-treatment compared to pre-treatment tumor specimens

    Measured: Approximately 5 years

  12. Part 2 Food Effect substudy: Cmax of SM08502 and SM08955 following single dose administration of SM08502 in fed and fasted states.

    Measured: Approximately 5 years

  13. Part 2 Food effect substudy: tmax of SM08502 and SM08955 following single dose administration of SM08502 in fed and fasted states.

    Measured: Approximately 5 years

  14. Part 2: AUC0-24 of SM08502 and SM08955 following single dose administration of SM08502 in fed and fasted states.

    Measured: Approximately 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2017
  2. Study start6 Nov 2017
  3. Primary completion14 Nov 2022
  4. Study completion14 Nov 2022

Why it stopped: Study was terminated due business reasons by Sponsor.

Resources

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
Masking
None (open label)
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03355066
Sponsor's protocol ID
SM08502-ONC-01
Status last verified
Aug 2024
First submitted
17 Nov 2017
Last updated
9 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Moroney MR, Woodruff E, Qamar L, Bradford AP, Wolsky R, Bitler BG, Corr BR. Inhibiting Wnt/beta-catenin in CTNNB1-mutated endometrial cancer. Mol Carcinog. 2021 Aug;60(8):511-523. doi: 10.1002/mc.23308. Epub 2021 May 26.

    PubMed 34038589

  • Tam BY, Chiu K, Chung H, Bossard C, Nguyen JD, Creger E, Eastman BW, Mak CC, Ibanez M, Ghias A, Cahiwat J, Do L, Cho S, Nguyen J, Deshmukh V, Stewart J, Chen CW, Barroga C, Dellamary L, Kc SK, Phalen TJ, Hood J, Cha S, Yazici Y. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Lett. 2020 Mar 31;473:186-197. doi: 10.1016/j.canlet.2019.09.009. Epub 2019 Sep 24.

    PubMed 31560935

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SM08502 in people with Solid Tumor, Adult, run by Biosplice Therapeutics, Inc. at 19 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 15 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: stopped early, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 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 was stopped early (reason given: Study was terminated due business reasons by Sponsor.). Results are not available in the source record.

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?

Part 1A, Part 1B: Maximum tolerated dose (MTD) of SM08502 based on the frequency and severity of dose-limiting toxicities (DLTs) (time frame: DLT period of 28 days per dose level). The study lists 36 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 NCT03355066, which also lists 2 linked publications.

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 9 Aug 2024.

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