International Society of Ocular Oncology (ISOO), Leiden NL June 17-21, 2022
UVEAL MELANOMA ABSTRACTS AND PRESENTATIONS
William Harbour of Univ. of Texas Southwestern in Dallas presented the Lex Van der Eb Lecture, with an update of several investigational novel therapies for uveal melanoma at Bascom Palmer/Univ. Miami and UT Southwestern.
An adjuvant (post-surgery) clinical trial is underway with quisinostat (an oral HDAC 1 & 4 inhibitor), inpatients with high-risk Class 2 UM Castle GEP prognostic status.
In metastatic UM, a clinical trial is open at Univ. Miami for a unique combination of relatlimab
(a LAG3 inhibitor) and nivolumab (PD-1 inhibitor). 22 patients are enrolled to-date.
Dr. Harbour concluded with an observation that BAP-1 loss triggers Class 2 GEP status,
which caused M2 (cell mitosis) polarization and tumor immune microenvironment- immunosuppression, via activation of the PROS1 and MERTK pathways (not seen in Class 1).
This leads to CD8 T-cell exhaustion, inhibitory Tregs, NK cells.
Thais Tong of the Leiden Univ. Medical Center presented an abstract in metastatic uveal melanoma, updated since ASCO 2022. The CHOPIN trial has enrolled 8 patients in 2 cohorts, to evaluate IV therapy of ipilimumab + nivolumab, alternating with two courses of Delcath/melphalan percutaneous hepatic infusion. While this study is ‘highly-investigational’,
initial results indicate an overall response rate of 71%, with 1 Complete Response, 5 Partial Responses and 2 Stable Disease. Preliminary follow-up is 22 months, with median progression-free survival 22 months. So far, no deaths on-study. The randomized cohort of the CHOPIN study is currently underway in the Netherlands, as described by Dr. Kapitejn (LUMC) Dr. John (Delcath) in an ACIS podcast interview conducted at ISOO in Leiden.
Carol Shields participated in a mini-symposium, with a presentation of a Phase 1b/2 trial (NCT03052127), which was a retrospective analysis assessing the visual acuity of patients following treatment with plaque radiotherapy, compared with prospective data on visual acuity in subjects with early-stage choroidal melanoma treated with AU-011 (a ‘virus-like’ particle targeted delivery of a potent cytotoxic drug) by intravitreal administration into the back of the eye and laser activation. Based on initial results in 43 choroidal melanoma patients in Phase Ib, Dr. Cadmus Rich of Aura Biosciences announced at the symposium (and an ACIS podcast interview) that the randomized Phase II study (NCT04417530) is now open for enrollment in 22 US clinical sites, to evaluate both dose escalation and repeat dose along with efficacy and safety.
Richard Carvajal participated in a mini-symposium, with a presentation on SD-101 (a Class C Toll-like Receptor-9 agonist), which is administered via a pressurized/pulsed catheter inserted into the liver for the treatment of metastatic uveal melanoma. The early Phase I results have demonstrated a favorable safety profile thus far. Dr. Steven Katz of Trisalus Life Sciences announced at ISOO (and in an ACIS podcast interview) that an ongoing Phase I/Ib trial is enrolling metastatic uveal melanoma patients in 5 US clinical sites. The PERIO-1 study (NCT04935229) is now evaluating the combination of SD-101 and the immune checkpoint inhibitors intravenous ipilimumab and nivolumab by dose escalations.
Marlana Orloff from Thomas Jefferson Univ. presented her center’s long-term clinical results in metastatic uveal melanoma patients receiving tebentafusp (KIMMTRAK®) in clinical trials
IMCgp100 -102 and -202. Among 35 patients with 3 years follow-up from start of therapy,
13 patients (37%) were identified with Overall Survival greater than 3 years. Key patient characteristics: median 3 prior lines of therapy for met. UM, 6 patients received tebe
pre- immune-checkpoint inhibitor (ICI), 10 patients received tebe before liver directed therapy (LDT).
Summary of long-term clinical observations: Median time one Tebe was 17 months,
Median Post-Tebe lines of therapy was 3, 10 patients received ICI post-tebe, 7 patients
received LDT post-tebe. Median Overall Survival from initial Metastatic Disease was 68 months.
Median OS from time on tebe was 44 months, with 8 patients treated beyond progression from tebe. Dr. Orloff noted a lack of genomic information in this cohort, and a need for future correlation with these outcomes. Also, other centers should consider evaluating their tebe-treated patients for additional outcomes such as prior and subsequent therapies, to help
inform future trials involving clinical combinations and sequences with tebentafusp.
Lab finding on immune status of metastatic uveal melanoma by Dr. Gulcin Gezgin of the Netherlands: Presence of tumor-Infiltrating lymphocytes (CD3, CD4, CD8, CD20, PD-1) don’t have prognostic value in Met. UM. Tumor-infiltrating macrophages are prognostic in primary UM (CD68 and CD162) and Met. UM (CD68). CD20 peri-tumoral infiltrates are prognostic in Met. UM. CD68 and CD163 peri-tumoral infiltrates correlate with desmoplastic growth pattern.
A Cure In Sight sponsored the first “ISOO Fellow Merit Award”, in honor of Dr. Jerry Shields.
The honored Fellow, Mrittika Sen MD, is from the Centre for Sight Superspeciality Eye Hospital, Hyderabad India. From left, Dr. Sara Lally and Dr. Carol Shields from Wills Eye Hospital in Philadelphia, Dr. Sen, Dr. Martine Jager from Leiden Univ. Medical Center and President of the ISOO 2022 Congress, and Kevin from ACIS.
Additional Abstracts and Posters:
Conditional survival of uveal melanoma using the Cancer Genome Atlas (TCGA) classification (Simplified Version) in 1001 Cases. Objective: To understand conjunctional prognosis for Uveal Melanoma metastasis using the Cancer Genome Atlas (TCGA) based metastasis free survival at 1 through 6 years.
Conclusion:Survival outcomes for Uveal Melanoma as non-conditional (let presentation) and conditional (metastasis-free survival) reveal reduction in metastatic risk over time.
Uveal melanoma patient reported outcomes (PROMS). Objective: To report on the Uveal melanoma Patients reported outcomes (PROMS) following the operation.
Conclusion: PROMS is a powerful tool that can assist us with understanding the healing process from the patient’s point of view. Is is essential when placing the patient’s needs in the center.