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Also known as Toll-like receptor 9, nelitolimod
SD-101 · 3 trials · 3 indications
Only participants in cohort 2, who achieve testosterone recovery to non-castrate levels (\>150 ng/dL) at 15 months, will be analyzed for the primary endpoint. The rate of PSA \< nadir + 2 ng/mL at 15 months from the start of radiotherapy and cycle 1, day 1 of pembrolizumab, among participants whose testosterone recovers to non-castrate levels (\>150 ng/dL). The point estimate of the rate of PSA \< nadir + 2 ng/mL will be obtained with its 95% confidence interval for participants by arm in cohort 2. All participants who receive any part of a dose of RT, SD-101 or pembrolizumab will be analyzed for efficacy.
Adverse events occurring on study will be summarized for all participants that received study intervention (including pembrolizumab, SD-101, SBRT to prostate, SBRT to oligometastatic sites) by maximum toxicity grade across study arms.
The primary endpoint is the number and frequency of adverse events related to cryoablation and hepatic artery infusion of SD-101 in combination with durvalumab and tremelimumab. Adverse events (AEs) during the 6 months following Cryo+SD-101 will be recorded. The NCI CTCAE version 5.0 will be used to grade adverse events. Incidence of AEs will be summarized by event type, grade and body system. Particularly, the rates of infusion reactions, major bleeding, major infection, and grade 3 or above non-infection adverse events will be reported. The proportion of patients having each type of adverse event will be summarized along with a corresponding 90% confidence interval calculated using the exact method. The rate and 90% exact CI of subjects who experience serious adverse events will also be reported.
As a measure of safety, adverse events will be graded according to CTCAE v5.0
A standard 3+3 dose-escalation design will be employed to determine the MTD or optimal biologic dose.
| Arm | Type | Description |
|---|---|---|
| Cohort 1, Arm 1: Prostate Only Sites (ADT, SBRT, Pembrolizumab) | EXPERIMENTAL | Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement. |
| Cohort 1, Arm 2: Prostate Only Sites (ADT, SBRT, Pembrolizumab, SD-101) | EXPERIMENTAL | Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. TLR9 agonist SD-101: Injected into the dominant prostatic tumor lesion at time of fiducial marker placement (1-5weeks prior to Cycle 1 Day 1) and 1-3 weeks after Cycle 1 Day 1 Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement. |
| Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab) | EXPERIMENTAL | Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland and oligometastatic sites via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement. |
| Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101) | EXPERIMENTAL | Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. TLR9 agonist SD-101: Injected into the dominant prostatic tumor lesion at time of fiducial marker placement (1-5weeks prior to Cycle 1 Day 1) and 1-3 weeks after Cycle 1 Day 1 Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland and oligometastatic sites via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement. |
| SD-101 | EXPERIMENTAL | Participants will be treated with cryoablation and intrahepatic artery infusion of SD-101. This treatment will be followed by administration of the immune checkpoint inhibitors Tremelimumab and Durvalumab (STRIDE regimen). Tremelimumab 300mg will be given intravenously once, 7-10 days after cryoablation + SD-101. Durvalumab 1500mg will be given intravenously at the same time as Tremelimumab, and then every 28 days (on day 1 of every subsequent cycle). |
| Name | Type | Description |
|---|---|---|
| Pembrolizumab | DRUG | 200 mg IV every 21 days for up to 13 doses (Arms 1 and 2) |
| SD-101 | DRUG | 5 mg will be delivered to the dominant prostatic tumor lesion at time of fiducial marker placement (1-5 weeks prior to Cycle 1, Day 1) and and 1-3 weeks after Cycle 1 Day 1 |
| Leuprolide acetate | DRUG | 22.5 mg will be given intramuscularly (IM). First injection 3 months prior to Cycle 1 Day 1. Intermittent androgen deprivation therapy will be given every 3 months starting Cycle 1, Day 1 for 3 additional doses. |
| Abiraterone Acetate | DRUG | 1000 mg oral dosage will be given daily for 3 months prior to Cycle 1, Day 1 and daily for 9 months starting Cycle 1, Day 1. |
| Prednisone | DRUG | 5 mg oral dosage will be given daily for 3 months prior to Cycle 1 Day 1 and daily for 9 months starting Cycle 1, Day 1. |
| Stereotactic Body Radiation Therapy | RADIATION | 7 Gy x 5 fractions (35 Gy total) 1-2 weeks after fiducial marker placement and simulation over 10-14 days. |
| Cryotherapy | DEVICE | Cryoablation of liver |
| Tremelimumab | DRUG | Anti-CTLA4 |
| Durvalumab | DRUG | Anti-PDL1 |
| anti-PD-1 | BIOLOGICAL | In the Phase 1b, anti-PD-1 will be administered together with SD-101 |
Inclusion Criteria: 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be \>=18 years of age on day of signing informed consent. 3. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 4. Histologically documented a...
SD-101 is an investigational cancer therapy being studied in hepatocellular carcinoma, locally advanced pancreatic adenocarcinoma, and prostate cancer. It is being developed by TriSalus Life Sciences, Inc. (TLSI) and is currently in Phase 1 clinical development. It is not approved for any indication.
SD-101 targets TLR9, a receptor involved in innate immune activation. By stimulating TLR9, SD-101 is designed to trigger an immune response against tumor cells. It is a small molecule being studied in several solid tumor types.
SD-101 is being developed by TriSalus Life Sciences, Inc., which trades under the ticker TLSI. The company is running clinical trials of SD-101 in hepatocellular carcinoma, locally advanced pancreatic adenocarcinoma, and prostate cancer.
SD-101 is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA for any indication. The Phase 1 trials are evaluating its use in hepatocellular carcinoma and locally advanced pancreatic adenocarcinoma.
SD-101 is being studied in three registered trials: NCT06710223 in hepatocellular carcinoma, NCT05607953 in locally advanced pancreatic adenocarcinoma, and NCT03007732 in prostate cancer. The first two are Phase 1 and active but not recruiting; the prostate cancer trial is Phase 2 and completed.