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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05084859




Registration number
NCT05084859
Ethics application status
Date submitted
24/09/2021
Date registered
20/10/2021
Date last updated
20/10/2022

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
SM08502-ONC-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Castration-resistant Prostate Cancer 0 0
Non-small Cell Lung Cancer 0 0
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SM08502
Treatment: Drugs - Abiraterone
Treatment: Drugs - Prednisone
Treatment: Drugs - Docetaxel
Treatment: Drugs - FOLFIRI Protocol
Treatment: Drugs - Panitumumab

Experimental: CRPC (Castration Resistant Prostate Cancer) - SM08502 + Abiraterone/Prednisone - Part 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.

Experimental: NSCLC (Non-Small Cell Lung Cancer) - SM08502 + Docetaxel - Part 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.

Experimental: CRC (Colorectal Cancer) - SM08502 + FOLFIRI/Panitumumab - Part 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).


Treatment: Drugs: SM08502
SM08502 to be administered orally.

Treatment: Drugs: Abiraterone
Abiraterone to be administered orally.

Treatment: Drugs: Prednisone
Prednisone to be administered orally.

Treatment: Drugs: Docetaxel
Docetaxel to be administered intravenously.

Treatment: Drugs: FOLFIRI Protocol
FOLFIRI Protocol to be administered intravenously.

Treatment: Drugs: Panitumumab
Panitumumab to be administered intravenously.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1 - Incidence of Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Consent date to 28 days after the last dose of study treatment
Primary outcome [2] 0 0
Part 1 - Maximum tolerated dose (MTD) of SM08502 when combined with standard of care agents.
Timepoint [2] 0 0
DLT period of 21 or 28 days per dose level depending on cycle length
Primary outcome [3] 0 0
Part 1 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Part 1 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [4] 0 0
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.
Primary outcome [5] 0 0
Part 1 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Part 1 - Plasma drug concentration
Timepoint [6] 0 0
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.
Primary outcome [7] 0 0
Part 2 - Incidence of Safety and tolerability of SM08502
Timepoint [7] 0 0
Consent date to 28 days after the last dose of study treatment
Primary outcome [8] 0 0
Part 2 - Objective response rate
Timepoint [8] 0 0
Approximately 5 years
Secondary outcome [1] 0 0
Part 1 - Objective Response rate
Timepoint [1] 0 0
Approximately 5 years
Secondary outcome [2] 0 0
Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Part 2 - Blood samples for measurement of the plasma levels of SM08502 and its metabolite
Timepoint [5] 0 0
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.

Eligibility
Key inclusion criteria
Key

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:

i. CRPC - Subjects with progressive disease in the setting of medical or surgical
castration (i.e., castration-resistant prostate cancer).

ii. 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.

iii. 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:

i. 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.

ii. 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.

iii. 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.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant or lactating.

2. Women of childbearing potential (WOCBP) must agree to follow the contraceptive
guidelines as outlined in protocol.

3. Men of reproductive potential must agree to follow the contraceptive guidelines as
outlined in protocol.

4. Subjects with a QTc (Fridericia's) prolongation > CTCAE v5.0 Grade 1 (>480 msec) at
Screening.

5. Subjects with clinically significant ventricular tachycardia (VT), atrial fibrillation
(AF), ventricular fibrillation (VF), second- or third-degree heart block.

6. 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)..

7. Subjects with active infection (e.g., requiring antibiotic therapy).

8. Organ transplant recipients.

9. Subjects with untreated, progressing, or known symptomatic brain metastasis.

10. 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.

11. Subjects with known hypersensitivity to any excipients in the study drug formulation.

12. 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.

13. Subjects with known active human immunodeficiency virus (HIV), hepatitis B virus
(HBV), or hepatitis C virus (HCV) infection.

14. Subjects considered by the Investigator to be unsuitable for the study for any other
reason.

15. Subjects with chronic liver disease or dysfunction and a Child-Pugh score of B or C.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Saint Vincent's Hospital - Darlinghurst
Recruitment hospital [3] 0 0
Icon Cancer Care-South Brisbane - South Brisbane
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital (TQEH) - Woodville South
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
4215 - South Brisbane
Recruitment postcode(s) [4] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Maine
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biosplice Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05084859
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Darrin Beaupre, MD, PhD, CMO
Address 0 0
Biosplice Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries