Abstract 1198P
Background
RYZ101 (225Ac-DOTATATE) is an alpha-emitting radiopharmaceutical in development for SSTR2+ solid tumors. Alpha-particles have a shorter path length/higher linear energy transfer than beta-particles, causing more frequent double-strand DNA breaks and potentially improved therapeutic index. ACTION-1 (NCT05477576) is a 2-part, global, randomized, controlled, open-label, phase 1b/3 trial of RYZ101 in advanced, well-differentiated SSTR+ GEP-NETs progressing after 177Lu-SSA therapy. Herein, we report results from the phase Ib portion of the trial.
Methods
The phase Ib portion had a dose de-escalation/Bayesian optimal interval design with boundaries based on a dose-limiting toxicity (DLT) rate of 25%. Patients (pts) received RYZ101 IV q8w x4 cycles. Planned dose levels (n=6/level): Level 0 (starting dose) 120kBq/kg; Level –1 90kBq/kg; Level –2 60kBq/kg. DLT was assessed for 56d after the first RYZ101 dose. Treatment-emergent adverse events (TEAEs) were graded by NCI-CTCAE v5.0. Dose de-escalation decisions/safety data were overseen by a Data Review Committee. Tumor response was assessed locally by RECIST v1.1.
Results
17 pts have received at least one dose of RYZ101 at 120kBq/kg (4 doses: 6 pts; 3 doses: 2 pts; 2 doses: 8 pts; 1 dose: 1 pt; median 8.9MBq). Baseline characteristics: median age 63y; male (n=11); ECOG PS 0/1 (n=10/7); primary tumor site GI/pancreas (n=12/5). No DLTs, no dose de-escalation and no treatment-related serious AEs (SAEs) occurred. TEAEs requiring dose reductions occurred in 2 pts (G2 thrombocytopenia, n=2). G3/4 TEAEs occurred in 6 pts, 3 related to RYZ101 (lymphopenia, n=2; weight decreased, n=1). SAEs occurred in 4 pts (all unrelated). Confirmed objective response was seen in 5 evaluable pts. Updated efficacy data will be provided at the congress.
Conclusions
RYZ101 was well tolerated and a fixed dose of 10.2MBq was declared the recommended phase 3 dose. Initial data suggest promising efficacy. Part 2 (phase 3) is enrolling and will compare RYZ101 at 10.2MBq q8w for 4 cycles with standard of care in pts with advanced SSTR2+ GEP-NETs progressing following prior 177Lu-labeled SSAs.
Clinical trial identification
ACTION-1 (NCT05477576).
Editorial acknowledgement
Editorial assistance for this abstract was provided by Lee Miller (Miller Medical Communications Ltd). This work was funded by the study sponsor (RayzeBio Inc).
Legal entity responsible for the study
RayzeBio Inc.
Funding
RayzeBio Inc.
Disclosure
J. Strosberg: Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Advisory Board: Novartis, Tersera; Financial Interests, Institutional, Principal Investigator: Merck, Novartis, Alphamedix; Financial Interests, Personal, Advisory Role: Novartis. G. Ulaner: Financial Interests, Personal, Speaker’s Bureau: GE Healthcare, Lantheus; Financial Interests, Institutional, Research Grant: GE Healthcare, Lantheus, Nuclidium, Curium, RayzeBio, ImmaginAb, BriaCell, POINT; Financial Interests, Personal, Advisory Role: GE Healthcare, Lantheus, Nuclidium, POINT. H.P. Soares: Financial Interests, Personal, Advisory Board: TerSera, Ipsen, AstraZeneca, Novartis, ITM. L.B. Anthony: Financial Interests, Institutional, Principal Investigator: Rayzebio. H. Jacene: Financial Interests, Personal, Invited Speaker: Monrol, ITM; Financial Interests, Personal, Member of Board of Directors: SNMMI; Financial Interests, Personal, Royalties: Cambridge University Press; Financial Interests, Institutional, Funding: Blue Earth Diagnostics; Financial Interests, Personal, Speaker, Consultant, Advisor: Blue Earth Diagnostics, Spectrum Dynamics. D. Ferreira: Financial Interests, Personal, Full or part-time Employment: RayzeBio, Bayer; Financial Interests, Personal, Stocks or ownership: RayzeBio, Bayer, Medtronic. J. Li: Financial Interests, Personal, Full or part-time Employment: RayzeBio; Financial Interests, Personal, Stocks or ownership: RayzeBio. K. Ma: Financial Interests, Personal, Full or part-time Employment: RayzeBio; Financial Interests, Personal, Stocks or ownership: RayzeBio. J. Rearden: Financial Interests, Personal, Stocks or ownership: RayzeBio; Financial Interests, Personal, Full or part-time Employment: RayzeBio. S. Moran: Financial Interests, Personal, Full or part-time Employment: RayzeBio; Financial Interests, Personal, Stocks or ownership: RayzeBio. T. Hope: Financial Interests, Institutional, Research Funding: Clovis Oncology, Philips, GE Healthcare, Lantheus, Janssen, The Prostate Cancer Foundation, The National Cancer Institute; Financial Interests, Personal, Advisory Role: Ipsen, Bayer, BlueEarth Diagnostics, RayzeBio, Curium; Financial Interests, Personal, Stocks or ownership: RayzeBio, Curium. M. Morris: Financial Interests, Personal, Advisory Board: Gentem Health, Softhread; Financial Interests, Personal, Full or part-time Employment: AMIT; Financial Interests, Personal, Ownership Interest: AMIT, Gentem Health, Softhread; Financial Interests, Personal, Principal Investigator: AMIT; Financial Interests, Institutional, Proprietary Information: AMIT; Financial Interests, Institutional, Sponsor/Funding: AMIT. All other authors have declared no conflicts of interest.
Resources from the same session
1170P - Survival outcome prediction of primary melanoma tumours from histology images using deep learning
Presenter: Céline Bossard
Session: Poster session 13
1171P - Evaluation of the transcriptomic presence of tumor associated antigens (TAAs) from antibody drug conjugates (ADCs) and PD-L1 in melanoma: Options for new clinical opportunities
Presenter: Jorge Bartolome
Session: Poster session 13
1172P - Analysis of the microbiome of metastatic melanoma patients with complete response to immunotherapy
Presenter: Marin Golcic
Session: Poster session 13
1173P - NRAS mutation as an independent prognostic factor for resectable Chinese acral melanoma
Presenter: Yu Xu
Session: Poster session 13
1174P - Sex differences in advanced melanoma in Spain: Results from the prospective real-world study GEM 1801
Presenter: Eva Muñoz Couselo
Session: Poster session 13
1175P - Return to work after neoadjuvant versus adjuvant immunotherapy in stage III melanoma patients
Presenter: Judith Lijnsvelt
Session: Poster session 13
1176P - Planned drug holidays during immunotherapy in advanced and metastatic melanoma patients: A nation-wide study
Presenter: Anna Czarnecka
Session: Poster session 13
1177P - Assessment of tumour burden reduction per photography vs magnetic resonance imaging in patients with locally advanced basal cell carcinoma receiving sonidegib 200 mg
Presenter: Ralf Gutzmer
Session: Poster session 13
1178P - Melanoma incidence rises for pediatrics: 15-year nationwide retrospective cohort study in Korea (2004-2019)
Presenter: Jisu Oh
Session: Poster session 13
1179P - The underestimated skin cancer risk after liver transplantation: A meta-analysis of 147154 patients
Presenter: Amr Ehab El-Qushayri
Session: Poster session 13