A Cure in Sight attended the American Society of Clinical Oncology (ASCO) June 3-6, 2022. We had an advocacy booth and made some great connections. A summary of Uveal Melanoma presentations and abstracts are below. Lot’s of exciting research is happening!

A. High-Interest:

FRIDAY JUNE 3, 2022: Education Session – Room S100a
New Drugs in Oncology: Incorporation Into Practice
Primary Track: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

❖2:47 PM EDT Tebentafusp for Uveal MelanomaReviewer/Speaker: Melinda Lynne Yushak, MD, MPH | Winship Cancer Institute of Emory University Data and reviewer comments as presented in live session.
In the Phase III trial for FDA approval, 245 patients with newly-diagnosed HLA A*02:01 positive OM received tebentafusp. Overall Survival improvement of 5.7 months, with 1 year OS 73% for tebentafusp-treated patients (vs 59% for investigator choice therapy group). Progression-Free Survival was also greater for tebentafusp-treated patients (31% vs. control group 19% at
6 months). Survival improvement was also noted among patients who experienced met. disease progression while taking tebetafusp. Adverse events 89% cytokine release syndrome (1% >grade 3), 83% rash (18% >grade 3). Toxicities likely less after cycle 3 or 4. Practical issues: need specialized centers familiar with observing/treating cytokine release syndrome, initial three dose-escalating treatments are given in-hospital, cost of travel, hospital and drug, but this is the first drug for OM with a survival benefit and will likely be a standard of care. Open questions
will be among newly-diagnosed and relapsed/refractory OM patients for proper sequencing liver- directed therapy and tebentafusp.

SUNDAY JUNE 5, 2022 Hall A (900am)
Poster Session Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

❖Abstract: 2651 Poster: 305 Safety and efficacy of etigilimab in combination with nivolumab in select recurrent/advanced solid tumors. Presenter: Meredith McKean, Sarah Cannon Res. Inst. Etigilimab (etig), a humanized IgG1 monoclonal antibody, blocks TIGIT interaction with PVR (poliovirus receptor) and inhibits downstream signaling with target cell killing. Preliminary update from ACTIVATE, an open-label Phase 1b/2 study is evaluating further efficacy, safety, tolerability and PK/PD of etig + nivolumab. So far 6 patients enrolled with metastatic OM, with 1 Partial Response and 2 Stable Disease (8, 7 and 5 months durations, ongoing). Sites at Sarah Cannon, MDACC, Angeles Clinic, Dana Farber, Duke, Marin Ca Care, Mayo Scottsdale/Rochester,

Univ Mich, Royal Marsden UK.

MONDAY JUNE 6, 2022 POSTER SESSION Hall A Melanoma/Skin Cancers (215pm)

❖Abstract: 9560 Poster: 153 Safety and efficacy of combined melphalan percutaneous hepatic perfusion (M-PHP) and ipilimumab plus nivolumab (IPI+NIVO) in metastasized uveal melanoma (mUM): First results of the phase Ib part of the CHOPIN trial. Presenter: Thaïs M.L. Tong, MD, MSc | Leiden University Medical Center, Department of Medical Oncology/Radiology

Eight patients with confirmed measurable hepatic mUM treated-PHP and Ipi limumab + Nivoolumab (either 1mg/kg or 3 mg/kg). Best Response: 1 complete response, 5 partial responses and 1 stable disease accounting for an objective response rate (ORR) of 85.7%. At a median follow- up time of 20.2 months, 4 pts have an ongoing response. Currently the median PFS is 22.4 months, and all pts are still alive. This is a very small study, and we hope to discuss further with the investigator at ISOO in Leiden NL mid-June 2022.

❖Abstract: 9510 Poster: 104 FOCUS phase 3 trial results: Percutaneous hepatic perfusion (PHP) with melphalan for patients with ocular melanoma liver metastases (PHP-OCM-301/301A). Presenter: Jonathan S. Zager, MD | H. Lee Moffitt Cancer Center and Research Institute
Objective Response Rate among 71 PHP-melphalan patients was 36.3%, (7 Complete Responses and 26 Partial Reponses) and 12.5% among 32 Best Available Care patients (4 Partial Responses). Median Duration of Response was 14 months for PHP patients and not calculable for BAC patients. Median Progression Free Survival was 9.03 months among PHP patients and 3.12 months among BAC patients. The median Overall Survival was 20.53 months among PHP patients and 14.06 months among BAC patients.

❖Abstract: 9511 Poster: 105 First interim analysis of the SirTac trial: A randomized phase II study of SIRT and DSM-TACE in patients with liver metastases from uveal melanoma. Presenter: Caroline-Anna Anna Peuker, MD | Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology SIRT: Selective Internal Radiation Therapy with Yttrium-90-bearing resin microspheres DSM-TACE: Transarterial Chemoembolization with Cisplatin and degradable starch microspheres; EmboCept S Objective Responses: 1 partial response in both arms, stable disease in 20 pts in the SIRT arm, and 20 pts in the TACE arm. Median Progression-Free Survival in the Per-Protocol population was 4.9 mo in the SIRT arm vs 2.2 mo in the TACE arm (p=0.037), with a higher median “liver-PFS” in the SIRT vs TACE arm (8.3 vs 2.2, p=0.026).

No safety data were reported. The study continues recruitment.

❖Abstract: LBA9509 (Late-breaking Abstract) Poster: 103
Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases, first results from a phase III randomized controlled multicenter trial
(the SCANDIUM trial). Presenter: Roger Olofsson Bagge, MD, PhD | Wallenberg Centre

for Molecular and Translational Medicine, University of Gothenburg

93 newly-diagnosed Metastatic uveal melanoma patients randomized to IHP or best available care. The Overall Response Rate (ORR) in the IHP group was 40% (17/43) compared to 4.5% (2/44) in the control group (p<0.0001). The median hepatic-Progression Free Survival in the IHP group was 9.1 months compared to 3.3 months in the control group (p<0.0001). The median PFS in the IHP group was 7.4 months compared to 3.3 months in the control group (p<0.0001). There were 14 treatment-related serious adverse events in the IHP group, where vascular complication and infections were the most common side effects, compared to 13 in the control group where immunotherapy related side effects were most common. There was one treatment related death in the IHP group.

❖6:04pm Abstract: 9517 | Poster: 110 Newly updated activity results of alrizomadlin (APG-115), a novel MDM2/p53 inhibitor, plus pembrolizumab: Phase 2 study in adults and children with various solid tumors. Presenter: Meredith McKean, MD | Sarah Cannon Research Institute, Tennessee Oncology, PLLC Reviewed and Discussed by Kelly Olino MD, Yale Cancer Center Ongoing US/Australian multicenter trial evaluated alrizomadlin, an investigational MDM2-selective, small-molecule inhibitor, combined with pembrolizumab, in patients with unresectable/metastatic melanoma that progressed on I-O drugs. In the metastatic uveal melanoma cohort, among 15 patients treated 1 has obtained partial response (7%) and

10 patients experienced Stable Disease (67%; one patient now 2 yrs SD). Across the 130 enrolled patients in 6 disease cohorts, common treatment (alrizomadlin or pembrolizumab)-related adverse events nausea (62%), thrombocytopenia (39%), vomiting (38%), fatigue (38%). The study continues to enroll patients at UCLA, Sarah Cannon, MSKCC, Duke, Univ AZ, Wash. Univ St. Louis, Cleveland Clinic, Penn State, Next Oncology.

B. All Other Ocular Melanoma Abstracts

MONDAY JUNE 6, 2022 POSTER SESSION Hall A Melanoma/Skin Cancers (215pm)

Abstract: 9534 Poster: 127 Outcomes of combined ipilimumab/nivolumab in metastatic uveal melanoma: A prevalence meta-analysis. Presenter: Ceren Durer | SUNY Upstate Medical University Pooled literature analysis of 8 studies combining ipilimumab + nilvolumab in 379 Met UM patients. Overall Response rate 13.7%, Complete Response Rate 2.1%, Overall Survival ranged from 12.7 – 10.1 months. Most common side effects included diarrhea, colitis, hepatic toxicities (≥grade III 26.2%), skin disorders, hypothyroidism.

Abstract: 9543 Poster: 136 Metabolic complete responses (mCR) in patients with metastatic uveal melanoma (mUM) treated with image-guided injection (IGI) of PV-10. Presenter: Krysta McVay, RN | University of Texas MD Anderson Cancer Center
25 mUM patients with liver metastases have been treated; 16 patients received standard of care immune checkpoint inhibitor (ICI) during or post PV-10 treatment. With follow-up PET CTs at 1-3 yrs,

four patients experienced mCR (molecular complete Remission??) in all metastatic sites, including extrahepatic metastasis. …This study and data need UM expert review, Kevin to pursue.

Abstract: 9565 Poster: 158 Immune profiling of metastatic uveal melanoma and response to immune checkpoint inhibitors. Presenter: Yusra F. Shao, MD | Barbara Ann Karmanos Cancer Institute, Wayne State University
A total of 450 UM samples analyzed, with 108 treated with Immune Checkpoint inhibitors (ICI).
UM lacks traditional markers of response to ICI. Short Time on Treatment (TOT) seen in our study is consistent with Progression Free Survival of 3 to 5.5 months seen in clinical trials. High LAG3 expression was associated with a clinically significant improvement in TOT. Most tumors were PDL1 low in the entire UM (86%, 240/279) and ICI treated (62%, 55/89) cohorts, with 98% (257/263) of all UM samples having low Tumor Mutational Burden.

Abstract: 9585 Poster: 178 Treatment with tebentafusp beyond radiographic progressive disease (PD) in metastatic uveal melanoma (mUM). Presenter: Ryan J. Sullivan, MD | Massachusetts General Hospital …Among 183 tebe-treated patients following radiographic metastatic progression, a numerical benefit in post-progression OS favoring TBP was observed (HR 0.67, 95% CI). Patients receiving tebe were more likely to have favorable key prognostic factors at baseline or at time of progression.

An Overall Survival benefit observed for tebentafusp among mUM patients who have initial radiographic progression demonstrates that RECIST assessment (response rate) underestimates benefit.

Abstract: 9586 Poster: 179 Randomized phase II study of adjuvant sunitinib or valproic acid in high-risk patients with uveal melanoma: The final analysis of cohort 1. Presenter: Rino S. Seedor, MD | Sidney Kimmel Medical College of Thomas Jefferson University
Both drugs met the primary endpoint with 2-year OS rates of 95.6% sunitinib and 90.7% valproic acid. Sunitinib showed a tendency for a better outcome until 3 years after randomization. Cohort 3 with adjuvant sunitinib in combination with VPA for 12 months is currently ongoing.

Abstract: TPS9610 Poster: 193b Capturing uveal melanoma (UM) global practice patterns and clinical outcomes in the collaborative ocular melanoma natural history (OMNi) study (NCT04588662).
Presenter: Joseph J. Sacco, MD, Clatterbridge Cancer Centre Trial design only, study underway.