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

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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. 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Biosplice Therapeutics, Inc.; Samumed LLC

Criteria

Key Inclusion Criteria:

1. Subjects with advanced solid tumors (as defined below):

1. 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)].

2. 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). Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. The indications eligible for Part 1B include: i. NSCLC, ii.TNBC, iii. CRPC, iv. CRC, v. Endometrial cancer, vi. Ovarian cancer

3. 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 at least two lines of prior therapy. The indications eligible for Part 2 include: i. NSCLC, ii. TNBC, iii. CRPC, iv. CRC, v. Endometrial cancer, vi. Ovarian cancer

2. Measurable or evaluable disease per RECIST 1.1 (Part 1A). For Parts 1B and 2, at least one 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.

3. 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. (Exception: Subjects may enter with continuing alopecia regardless of any CTCAE grade or with Grade 2 or better neuropathy.) The following intervals must elapse between end of last treatment and receiving the first dose of SM08502:

1. Chemotherapy: 3 weeks

2. Mitomycin C or a nitrosourea: 6 weeks

3. Radiotherapy: 3 weeks

4. Major surgery: 6 weeks

5. Targeted therapy, including monoclonal antibodies and immuno-oncology therapies:

4 weeks or 5 half-lives, whichever is shortest

6. Anti-hormonal therapy: 3 weeks. The exception is ADT for subjects with CRPC who are progressing on therapy, ADT may be continued in this study.

7. Experimental therapy: 4 weeks or 5 half-lives, whichever is shortest

8. Other locoregional therapy [e.g., radiofrequency ablation (RFA), TACE (transarterial chemoembolization), TARE (transarterial radioembolization), DEB-TACE (drug eluting bead transarterial chemoembolization)]: 6 weeks

4. Subjects must meet the following laboratory criteria at Screening for study entry:

1. 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

2. Renal function: measured or calculated creatinine clearance via Cockcroft-Gault formula >35 mL/min

3. Hematology: absolute neutrophil counts ≥ 1500/mm3, platelet counts ≥ 100,000/mm3, hemoglobin ≥ 9.0 g/dL Subjects with values within 10% of these limits deemed not clinically significant by the Investigator may be entered with the approval of the Sponsor's Medical Monitor.

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Key Exclusion Criteria:

1. Women who are pregnant or lactating

2. Women of childbearing potential (WOCBP) who do not agree to follow the contraceptive guidelines as outlined in the study protocol

3. Men of reproductive potential who do not agree to follow the contraceptive guidelines as outlined in the study 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 requiring antibiotic therapy

8. Subjects with a second malignancy unless adequately treated with no recurrence for 3 years. Subjects with a 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.

9. 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

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

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