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Castration-resistant Prostate CancerPhase 1NCT05084859

A Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Orally Administered SM08502 Combined With Hormonal Therapy or Chemotherapy in Subjects With Advanced Solid Tumors

A Phase 1 study testing SM08502, Abiraterone and Prednisone in people with Castration-resistant Prostate Cancer and Non-small Cell Lung Cancer, run by Biosplice Therapeutics, Inc. at 20 sites in 2 countries.

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 expansion study in adult subjects with advanced solid tumors. The study will evaluate the safety, tolerability, PK, and preliminary anti-tumor efficacy of SM08502 administered orally (PO), once daily (QD), following a 5 days on 2 days off treatment… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SM08502, Abiraterone and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
20 sitesin 2 countries
Study dates
3 Nov 2021to 20 Oct 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

  • 1.0. Part 1 - Subjects with advanced and/or metastatic solid tumors. Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. The tumor types include:
  • CRPC - Subjects with progressive disease in the setting of medical or surgical castration (i.e., castration-resistant prostate cancer).
  • NSCLC (adenocarcinoma subtype) - Subjects with no targetable mutations must have received a platinum-containing doublet chemotherapy regimen and a checkpoint inhibitor (either in combination or monotherapy, if indicated) and have progressed. Subjects with targetable mutations/alterations such as EGFR, ALK, or NTRK must have received prior targeted therapy and have progressed.
  • CRC - Subjects must have received one prior line of standard chemotherapy such as FOLFOX +/- a VEGF-inhibitor and have progressed or are intolerant of oxaliplatin based regimens.
  • 1.1. Part 2 - Subjects with advanced and/or metastatic solid tumors. Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. The tumor types include:
  • CRPC - Subjects with progressive disease in the setting of medical or surgical castration (i.e., castration- resistant prostate cancer). Subjects who have not received chemotherapy, are not candidates for chemotherapy, or refuse chemotherapy are eligible (Arm A). Subjects who have received chemotherapy are eligible (Arm B), however, more than 2 prior lines of chemotherapy in any setting are excluded.
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  • NSCLC (adenocarcinoma subtype) - Subjects with no targetable mutations must have received a platinum-containing doublet chemotherapy regimen and a checkpoint inhibitor (either in combination or monotherapy, if indicated) and have progressed. Subjects with targetable mutations/alterations such as EGFR, ALK, NTRK must have received prior targeted therapy and have progressed.
  • CRC - Subjects must have received one prior line of standard chemotherapy such as FOLFOX +/- either a VEGF-inhibitor or EGFR inhibitor (if indicated) and have progressed or are intolerant of oxaliplatin based regimens.
  • 2.0. Male or female subjects ≥ 18 years of age.
  • 3.0 Measurable or evaluable disease per RECIST 1.1 (Part 1). For Part 2, at least one measurable lesion per RECIST 1.1 that has not been previously irradiated. In CRPC subjects (Parts 1 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 for those without measurable disease.
  • 4.0. Subjects must have archived tumor specimens available for analysis Otherwise, a fresh tumor biopsy will be required at study entry.
  • 5.0.. 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.
  • The following intervals must elapse between end of last treatment and receiving the first dose of SM08502:
  • Chemotherapy: 3 weeks.
  • Mitomycin C or a nitrosourea: 6 weeks.
  • Radiotherapy: 3 weeks.
  • Major surgery: 6 weeks.
  • Targeted therapy, including monoclonal antibodies and immuno-oncology therapies: 4 weeks or 5 half-lives, whichever is shortest.
  • 6.0. Subjects must meet the following laboratory criteria at Screening for study entry:
  • Hepatic function: serum total bilirubin ≤ 1.5x upper limit of normal (ULN), AST/ALT ≤ 2.5x ULN. For subjects with Gilbert's syndrome, serum total bilirubin ≤ 3x ULN.
  • Renal function: measured or calculated creatinine clearance via Cockcroft-Gault formula >35 mL/min.
  • Hematology: absolute neutrophil counts ≥ 1500/mm3, platelet counts ≥ 100,000/mm3, hemoglobin ≥ 9.0 g/dL.
  • Coagulation: prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5x ULN.
  • 7.0. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • 8.0. Life expectancy > 3 months.
  • 9.0. Subjects must have no uncontrolled intercurrent illness.
  • 10.0 Subjects must have the ability to swallow and retain oral medication.
  • 11.0 Subjects must be willing to sign and provide informed consent and be capable of giving informed consent in accordance with the Institutional Review Board (IRB) / Ethics Committee (EC) policy.

Who cannot join

  • Women who are pregnant or lactating.
  • Women of childbearing potential (WOCBP) must agree to follow the contraceptive guidelines as outlined in protocol.
  • Men of reproductive potential must agree to follow the contraceptive guidelines as outlined in protocol.
  • Subjects with a QTc (Fridericia's) prolongation > CTCAE v5.0 Grade 1 (>480 msec) 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 (e.g., requiring antibiotic therapy).
  • Organ transplant recipients.
  • Subjects with untreated, progressing, or known symptomatic brain metastasis.
  • Subjects with a second malignancy unless adequately treated with no recurrence for 3 years. Subjects with a history of previous or recent adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of any source are eligible.
  • Subjects with known hypersensitivity to any excipients in the study drug formulation.
  • 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 considered by the Investigator to be unsuitable for the study for any other reason.
  • Subjects with chronic liver disease or dysfunction and a Child-Pugh score of B or C.

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

United States16 sites

  • University of Colorado, Anschutz

    Aurora, Colorado, 80045-2571

  • University of Colorado

    Aurora, Colorado, 80045

  • The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, LLC

    Cincinnati, Ohio, 45219

  • Duke Cancer Institute (DCI) - Duke Cancer Center

    Durham, North Carolina, 27710-2000

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 20176

  • Texas Oncology

    Fort Worth, Texas, 76104

  • START Midwest

    Grand Rapids, Michigan, 49546

  • Vanderbilt University

    Nashville, Tennessee, 37212

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021-0005

  • Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care

    Roanoke, Virginia, 24014

  • Texas Oncology-San Antonio Northeast

    San Antonio, Texas, 78217

  • UT Health San Antonio - Mays Cancer Center - Institute for Drug Development

    San Antonio, Texas, 78229

  • Maine Center for Cancer Medicine

    Scarborough, Maine, 04074-7172

  • Seattle Cancer Care Alliance (SCCA)

    Seattle, Washington, 98109-1023

  • The University of Arizona Cancer Center (UACC) - North Campus

    Tucson, Arizona, 85719-1478

  • START Mountain Region

    West Valley City, Utah, 84119

Other trials in United States

Australia4 sites

  • Chris O'Brien Lifehouse

    Camperdown, 2050

  • Saint Vincent's Hospital

    Darlinghurst, 2010

  • Icon Cancer Care-South Brisbane

    South Brisbane, 4215

  • The Queen Elizabeth Hospital (TQEH)

    Woodville South, 5011

Other trials in Australia

About this study

Official title: A Phase 1b, Open-Label, Dose-Escalation, Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Orally Administered SM08502 Combined With Hormonal Therapy or Chemotherapy in Subjects With Advanced Solid Tumors

This study is an open-label, multi-center, dose-escalation, dose expansion study in adult subjects with advanced solid tumors. The study will evaluate the safety, tolerability, PK, and preliminary anti-tumor efficacy of SM08502 administered orally (PO), once daily (QD), following a 5 days on 2 days off treatment schedule in combination with chemotherapy or hormonal therapy. Alternative dosing schedules may be explored in Part 1 if necessary. The recommended Part 2 dose and schedule for each combination will then be further evaluated in the Part 2 expansion.

Dosing will occur in 21- or 28-day cycles (depending on the combination partner) and treatment with SM08502 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.

Being tested
SM08502, Abiraterone, Prednisone, Docetaxel, FOLFIRI Protocol
Keywords
SM08502, pan Clk/Dyrk inhibitor
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms

What participants receive

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

  • SM08502Drug

    SM08502 to be administered orally.

  • AbirateroneDrug

    Abiraterone to be administered orally.

  • PrednisoneDrug

    Prednisone to be administered orally.

  • DocetaxelDrug

    Docetaxel to be administered intravenously.

  • FOLFIRI ProtocolDrug

    FOLFIRI Protocol to be administered intravenously.

  • PanitumumabDrug

    Panitumumab to be administered intravenously.

Study groups in NCT05084859
Study groupRoleWhat they receive
CRPC (Castration Resistant Prostate Cancer) - SM08502 + Abiraterone/PrednisoneExperimentalPart 1 (dose escalation cohorts) will evaluate SM08502 in subjects with advanced CRPC. Subjects will receive increasing doses of SM08502 with fixed doses of Abiraterone/Prednisone to determine the MTD and recommended Part 2 dose and schedule. Escalation will follow a 3+3+3 design within each cohort. Part 2 will further evaluate the recommended dose and schedule of SM08502 in subjects with advanced CRPC. Approximately 20 subjects will be enrolled.
Receives: Drug: SM08502; Drug: Abiraterone; Drug: Prednisone
NSCLC (Non-Small Cell Lung Cancer) - SM08502 + DocetaxelExperimentalPart 1 (dose escalation cohorts) will evaluate SM08502 in subjects with advanced NSCLC. Subjects will receive increasing doses of SM08502 with fixed doses of docetaxel to determine the MTD and recommended Part 2 dose and schedule. Escalation will follow a 3+3+3 design within each cohort. Part 2 will further evaluate the recommended dose and schedule of SM0850 in subjects with advanced NSCLC. Approximately 20 subjects will be enrolled.
Receives: Drug: SM08502; Drug: Docetaxel
CRC (Colorectal Cancer) - SM08502 + FOLFIRI/PanitumumabExperimentalPart 1 (dose escalation cohorts) will evaluate SM08502 in subjects with advanced CRC. Subjects will receive increasing doses of SM08502 with fixed doses of FOLFIRI plus panitumumab ( RAS wild type tumors) or with fixed doses of FOLFIRI (RAS mutant tumors) Escalation will follow a 3+3+3 design within each cohort. Part 2 will further evaluate the recommended dose and schedule of SM08502. Subjects that have RAS wild type tumors will receive FOLFIRI and panitumumab with SM08502 (n=15). Subjects that have RAS mutant tumors will receive FOLFIRI with SM08502 (n=15).
Receives: Drug: SM08502; Drug: FOLFIRI Protocol; Drug: Panitumumab

What is being measured

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

  1. Part 1 - Incidence of Treatment Emergent Adverse Events (TEAEs)

    As measured by NCI CTCAE version 5.0.

    Measured: Consent date to 28 days after the last dose of study treatment

  2. Part 1 - Maximum tolerated dose (MTD) of SM08502 when combined with standard of care agents.

    Based on frequency and severity of dose-limiting toxicities (DLTs).

    Measured: DLT period of 21 or 28 days per dose level depending on cycle length

  3. Part 1 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Maximum (Cmax) and minimum (Cmin) Plasma concentration of SM08502 and its metabolite SM08955.

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15, Day22) Cycle 2 (Day1, Day2) Cycle3-5 (Day1) and EOT. Each cycle is 21 or 28 days depending on tumor type.

  4. Part 1 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Area under the plasma concentration time curve (AUC) from zero to 24 hours: AUC0-24 for SM08502 and its metabolite SM08955

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15, Day22) Cycle 2 (Day1, Day2) Cycle3-5 (Day1) and EOT. Each cycle is 21 or 28 days depending on tumor type.

  5. Part 1 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Area under the plasma concentration time curve (AUC) from zero to the last measurable concentration: AUClast for SM08502 and its metabolite SM08955.

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15, Day22) Cycle 2 (Day1, Day2) Cycle3-5 (Day1) and EOT. Each cycle is 21 or 28 days depending on tumor type.

  6. Part 1 - Plasma drug concentration

    Maximum steady-state plasma drug concentration (Cmaxss) during a dosage interval.

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15, Day22) Cycle 2 (Day1, Day2) Cycle3-5 (Day1) and EOT. Each cycle is 21 or 28 days depending on tumor type.

  7. Part 2 - Incidence of Safety and tolerability of SM08502

    As measured by treatment emergent adverse events (TEAEs) as measured by NCI CTCAE version 5 from subjects treated at the recommended Part 2 dose and schedule.

    Measured: Consent date to 28 days after the last dose of study treatment

  8. Part 2 - Objective response rate

    Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Prostate Cancer Working Group 3 Criteria (PCWG3) where appropriate.

    Measured: Approximately 5 years

Secondary outcomes (5)

  1. Part 1 - Objective Response rate

    Tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Prostate Cancer Working Group 3 Criteria (PCWG3) where appropriate.

    Measured: Approximately 5 years

  2. Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Maximum (Cmax) and minimum (Cmin) Plasma concentration of SM08502 and its metabolite SM08955.

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15,) Cycle 2-5 (Day1). Each cycle is 21 or 28 days depending on tumor type.

  3. Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Area under the plasma concentration time curve (AUC) from zero to 24 hours: AUC0-24 for SM08502 and its metabolite SM08955

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15,) Cycle 2-5 (Day1). Each cycle is 21 or 28 days depending on tumor type.

  4. Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Area under the plasma concentration time curve (AUC) from zero to the last measurable concentration: AUClast for SM08502 and its metabolite SM08955.

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15,) Cycle 2-5 (Day1). Each cycle is 21 or 28 days depending on tumor type.

  5. Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite

    Maximum steady-state plasma drug concentration (Cmaxss) during a dosage interval.

    Measured: Sample collection timepoints: Cycle1 (Day1 (0,2,4,6, hrs), Day2, Day8, Day15,) Cycle 2-5 (Day1). Each cycle is 21 or 28 days depending on tumor type.

Timeline

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

  1. First posted20 Oct 2021
  2. Study start3 Nov 2021
  3. Primary completion20 Oct 2022
  4. Study completion20 Oct 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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05084859
Sponsor's protocol ID
SM08502-ONC-03
Status last verified
Aug 2024
First submitted
24 Sep 2021
Last updated
9 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SM08502, Abiraterone and Prednisone in people with Castration-resistant Prostate Cancer and Non-small Cell Lung Cancer, run by Biosplice Therapeutics, Inc. at 20 sites in 2 countries.

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 28 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 20 sites in United States, Australia. 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 1 - Incidence of Treatment Emergent Adverse Events (TEAEs) (time frame: Consent date to 28 days after the last dose of study treatment). The study lists 8 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 NCT05084859.

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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