In early June, A Cure In Sight attended the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Kevin and Kristen met with oncologists from all over the world at our Exhibit, and had the ‘rare’ opportunity to meet with our medical oncologists from Thomas Jefferson University during the Uveal Melanoma Poster Session (Drs. Marlana Orloff and Takami Sato)!
Results from Key Clinical Abstracts and Posters:
Abstract # 9509, Matteo Carlino (Rare Melanomas Rapid Oral Abstract presentation)
A first-in-human study of DYP688, an antibody drug conjugate delivering a direct Gq/11 inhibitor,
in patients with metastatic uveal melanoma (MUM) and other GNAQ/11 mutant melanomas.
Dr. Carlino and investigators in Australia, Germany, The Netherlands, France, Switzerland and the USA evaluated this unique targeted therapy in a Phase I dose-escalation and safety study. DYP688 is a humanized monoclonal antibody directed to PMEL17 which is a protein found abundantly in uveal melanoma cells.
The antibody is linked to a drug molecule (SDZ475) which inhibits GNAQ/11 oncogenic signaling (present in over 80% of uveal melanoma mutations), resulting in cell death. The Phase I study enrolled 60 metastatic
uveal melanoma patients across 7 dose/schedule levels. Almost 60% of patients had 2 prior lines of metastatic treatment (including 33% with prior tebentafusp) before enrolling on this study. The side effects in 10-25% of patients were increased calcium levels, dry mouth, fatigue, edema, anemia and constipation. There were no “dose-limiting toxicities” and so a maximum tolerated dose was not determined by this safety study. One patient with metastatic uveal melanoma achieved complete response, with an additional 10 UM patients achieving Partial Response and 26 achieving stable disease. The original sponsor Novartis appears to be in discussions to license DYP688 to another pharma for further development.
Abstract # 9590 David Reichstein (Uveal Melanoma Poster)
Independent validation of a 16-protein test to assess malignant potential of small uveal melanocytic tumors.
Ocular oncology investigators from five COOG sites collaborated with Castle Biosciences to evaluate
71 patients’ aqueous humor over time, to determine if their uveal melanocytic lesions (prior to diagnosis of uveal melanoma) express any of 16 proteins (along with tumor diameter) as a “predictor of high-risk” for development of cancer. The study resulted in validating this prognostic panel test, with a sensitivity of 91% specificity of 50%. While the aqueous humor protein marker panel may be helpful for monitoring these pre-cancerous lesions, it did not correlate (and does not replace) the established Castle GEP prognostic test for actual uveal melanoma tumors.
Abstract # 2508, Martin Wermke (Developmental Therapeutics Oral Abstracts Session)
Phase 1 clinical update of IMA203, an autologous TCR-T targeting PRAME in patients with PD1 refractory metastatic melanoma. NCT03686124
IMA203 is an autologous TCR-T therapy made from each patient’s T-cells, which specifically targets PRAME (found in about half of all uveal melanoma tumors). This Phase I study continues to enroll patients with a variety of solid tumors. Among 70 patients to-date, 16 patients have been enrolled with metastatic uveal melanoma. Ten of the uveal melanoma patients have already achieved a confirmed Objective Response, for an ORR rate of 67% in this small Phase I sub-population. This result appears larger than the 50% of ORRs achieved in 14 patients with cutaneous melanoma in this study. The study is open at sites in Boston, Philadelphia, Pittsburgh, Houston, Miami and cancer centers in Germany. We will continue to monitor the further development of IMA204 by Immatics, as another Pharma’s promising PRAME-targeted therapy is not being further evaluated in a later-stage study in UM patients.
Trials In-Progress (open for patient enrollment):
Abstract # TPS9613, Paul Nathan
A phase II randomised study to evaluate the antitumour activity of roginolisib (IOA-244), a novel non-ATP competitive and allosteric modulator inhibiting PI3Kδ, in patients with metastatic uveal melanoma
(OCULE-01). NCT06717126
This clinical trial is located at uveal melanoma medical oncology cancer centers in Europe, UK and the USA.
Eligible patients will have progressed following at least 1 prior immunotherapy treatment. Patients will be randomized to one of 3 treatment arms; Arm 1: (n=50) IOA-244 80mg daily, Arm 2: (n=25) Investigator’s choice of therapy, Arm 3: (n-10) IOA-244 40 mg daily. An extension study will be available for patients who have reached the 24-month efficacy evaluation timepoint, so they may continue to receive therapy and follow-up.
Abstract # TPS9597, Joseph Sacco, Marlana Orloff
A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab
in immune checkpoint inhibitor-naïve patients with metastatic uveal melanoma. NCT06581406
This clinical trial is open at uveal melanoma medical oncology cancer centers in Europe, UK, USA and Australia.
UM patients with one (or no) prior line of metastatic therapy are eligible. Patients who have had prior exposure to ICIs since the time of UM diagnosis, involvement of >33.3% of the liver, or a history of prior liver- or lesion-directed therapy are not eligible for enrollment. Enrolled patients (N = ~280) will be randomized 1:1 to receive either RP2 + nivo -or- ipi + nivo. RP2 is given by intra-tumoral injection (primarily liver metastases).