Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 13

1198P - Phase Ib portion of the ACTION-1 phase Ib/3 trial of RYZ101 in gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177Lu somatostatin analogue (SSA) therapy: Safety and efficacy findings

Date

21 Oct 2023

Session

Poster session 13

Topics

Tumour Site

Neuroendocrine Neoplasms

Presenters

Jonathan Strosberg

Citation

Annals of Oncology (2023) 34 (suppl_2): S701-S710. 10.1016/S0923-7534(23)01264-4

Authors

J. Strosberg1, G. Ulaner2, D. Halperin3, S.H. Mehr4, D. Li5, H.P. Soares6, L.B. Anthony7, S. Kotiah8, H. Jacene9, P.L. Kunz10, D. Ferreira11, J. Li12, K. Ma13, J. Rearden14, S. Moran15, T. Hope16, S. Singh17, M. Morris18

Author affiliations

  • 1 Gi Oncology, Moffitt Cancer Center, 33612 - Tampa/US
  • 2 Molecular Imaging And Therapy, Hoag Family Cancer Institute and University of Southern California, 92663 - Newport Beach/US
  • 3 Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 4 Nuclear Oncology, Nebraska Cancer Specialists - Midwest Cancer Center-Legacy, 68130 - Omaha/US
  • 5 Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, 91010 - Duarte/US
  • 6 Medical Oncology, Huntsman Cancer Institute - University of Utah, 84112 - Salt Lake City/US
  • 7 Medical Oncology, University of Kentucky Markey Cancer Center, 40506-0032 - Lexington/US
  • 8 Medical Oncology, Mercy Medical Center, 96002 - Baltimore/US
  • 9 Imaging, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 10 Yale Cancer Center, 333 Cedar Street, Po Box 208028, Yale University School of Medicine, 06520 - New Heaven/US
  • 11 Radiation Oncologist, RayzeBio, Inc., 92121 - San Diego/US
  • 12 Biometrics, RayzeBio, Inc., 92121 - San Diego/US
  • 13 Clinical Operations, RayzeBio, Inc., 92121 - San Diego/US
  • 14 Clinical Science, RayzeBio, Inc., 92121 - San Diego/US
  • 15 Medical Affairs, RayzeBio, Inc., 92121 - San Diego/US
  • 16 Medical Oncology, University of California San Francisco, CA, 94143 - San Francisco/US
  • 17 Medical Oncology, University of Toronto, Odette Cancer Center at Sunnybrook Health Sciences Center, M4N 3M5 - Toronto/CA
  • 18 Nuclear Oncology/theranostics Center Of Excellence, Advanced Molecular Imaging and Therapy (AMIT), Glen Burnie/US

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.