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

NCT ID: NCT05084859

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-03
• Study Completion Date: 2022-10-20

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.

Conditions

Castration-resistant Prostate Cancer; Non-small Cell Lung Cancer; Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SM08502

Intervention Type: DRUG

SM08502 to be administered orally.

Abiraterone

Intervention Type: DRUG

Abiraterone to be administered orally.

Prednisone

Intervention Type: DRUG

Prednisone to be administered orally.

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.

Group Type: EXPERIMENTAL

SM08502

Intervention Type: DRUG

SM08502 to be administered orally.

Docetaxel

Intervention Type: DRUG

Docetaxel to be administered intravenously.

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).

Group Type: EXPERIMENTAL

SM08502

Intervention Type: DRUG

SM08502 to be administered orally.

FOLFIRI Protocol

Intervention Type: DRUG

FOLFIRI Protocol to be administered intravenously.

Panitumumab

Intervention Type: DRUG

Panitumumab to be administered intravenously.

Interventions

SM08502

SM08502 to be administered orally.

Intervention Type: DRUG

Abiraterone

Abiraterone to be administered orally.

Intervention Type: DRUG

Prednisone

Prednisone to be administered orally.

Intervention Type: DRUG

Docetaxel

Docetaxel to be administered intravenously.

Intervention Type: DRUG

FOLFIRI Protocol

FOLFIRI Protocol to be administered intravenously.

Intervention Type: DRUG

Panitumumab

Panitumumab to be administered intravenously.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biosplice Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darrin Beaupre, MD, PhD, CMO

Role: STUDY_CHAIR

Biosplice Therapeutics, Inc.

Locations

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

Tucson, Arizona, United States

University of Colorado, Anschutz

Aurora, Colorado, United States

University of Colorado

Aurora, Colorado, United States

Maine Center for Cancer Medicine

Scarborough, Maine, United States

START Midwest

Grand Rapids, Michigan, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Duke Cancer Institute (DCI) - Duke Cancer Center

Durham, North Carolina, United States

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

Cincinnati, Ohio, United States

Vanderbilt University

Nashville, Tennessee, United States

Texas Oncology

Fort Worth, Texas, United States

Texas Oncology-San Antonio Northeast

San Antonio, Texas, United States

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

San Antonio, Texas, United States

START Mountain Region

West Valley City, Utah, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

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

Roanoke, Virginia, United States

Seattle Cancer Care Alliance (SCCA)

Seattle, Washington, United States

Chris O'Brien Lifehouse

Camperdown, , Australia

Saint Vincent's Hospital

Darlinghurst, , Australia

Icon Cancer Care-South Brisbane

South Brisbane, , Australia

The Queen Elizabeth Hospital (TQEH)

Woodville South, , Australia

Countries

United States; Australia

Other Identifiers

SM08502-ONC-03

Identifier Type: -

Identifier Source: org_study_id