KEY TAKEAWAYS
- The phase 1 PERIO-01 trial evaluated the hepatic arterial SD-101 using PEDD in MUM-LM. Researchers explored dose escalation alone or with nivolumab/ipilimumab over 2 outpatient cycles.
- Combining SD-101 via PEDD and systemic ICI showed promising clinical activity in MUM-LM, leading to Phase 2 expansion.
Metastatic uveal melanoma liver metastases (MUM-LM) are resistant to immune checkpoint inhibitors (ICIs) due to high myeloid-derived suppressor cell (MDSC) prevalence. Approved treatments like tebentafusp yield limited progression-free survival (median 3.3 months) with over 30% grade 3/4 adverse events. TLR9 agonists can polarize MDSCs, yet intra-tumoral drug delivery limitations persist.
The phase 1 PERIO-01 trial (NCT04935229) investigated hepatic arterial SD-101 via PEDD in MUM-LM. It explored dose escalation alone (Cohort A), with nivolumab (Cohort B), or with nivolumab + ipilimumab (Cohort C). SD-101 was administered across 2 outpatient cycles, with 3 weekly doses per cycle.
In the study, 53 patients received SD-101: 13 in Cohort A, 25 in Cohort B, and 15 in Cohort C. Median age was 65, with 45% females. 70% had prior MUM-LM treatment; 15% received tebentafusp. Notably, 28% had LM >5cm and 44% >10 LMs. One patient showed partial response (Cohort B 4 mg), ongoing for 258 days. Six others experienced reduced lesion size (SD), 3 ongoing at 168 days.
Median PFS was highest in Cohort B (2 mg) at 11.7 months, with an 86% disease control rate. Grade 3/4 treatment-related AEs occurred in 8% of subjects, varying by cohort (0% in A, 4% in B, 20% in C) for an overall rate of 21%. SD-101 PEDD led to reduced LM mMDSC levels and lowered expression of ARG1, CD163, and FASN. LM also showed immune activation with increased CD4+ and CD8+ T cells, decreased Treg, and elevated IFNg and IFNa2 gene expression.
Peripheral immune activation included increased proliferating CD8+ T and NK cells, plus higher IP-10, TNFa, IFNg, IL-2R, and IL-18. Of 25 patients whose ctDNA data was analyzed, 68% displayed decreased levels, with 28% showing complete clearance.
The researchers concluded that combining SD-101 via PEDD and systemic ICI showed clinical efficacy, with a median PFS of 11.7 months. The Phase 2 of PERIO-01 aims to expand on the optimal dose.
Source: https://jitc.bmj.com/content/11/Suppl_2/A1712
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04935229
Patel SP, Carvajal R, Montazeri K, et al1534 Clinical activity of SD-101 with immune checkpoint inhibition (ICI) in metastatic uveal melanoma liver metastasis (MUM-LM) from the PERIO-01 Phase 1 trialJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.1534
