Clinical Trials – Targeted Alpha-Emitter PRRT RYZ101/RYZ401

Update – 1 April 2026

RYZ401: New Alpha‑Emitter Trial (PRRT‑Naïve Only)

In January 2026, RayzeBio (now part of Bristol Myers Squibb) opened a new first‑in‑human trial for RYZ401, titled “Study of RYZ401 in Subjects With Solid Tumors Expressing SSTRs” (NCT07165132). This Phase 1/2 study aims to:

determine the recommended Phase 2 dose (RP2D)
define the optimal treatment schedule
assess safety and tolerability
evaluate early signs of efficacy

The trial includes NETs and other SSTR‑expressing solid tumours, including meningioma.

Important: RYZ401 excludes anyone who has ever received PRRT (Lu‑177 or Y‑90). This makes it a PRRT‑naïve trial.

1 April 2026: The first three patients have now been treated at Huntsman Cancer Institute, Utah. click here

Update – 27 December 2023

Bristol Myers Squibb acquires RayzeBio, adding a major radiopharmaceutical platform to its oncology portfolio. This highlights the growing strategic importance of radioligand therapy (RLT), especially alpha‑emitters, across NETs, prostate cancer, and other solid tumours. Bristol Myers Squibb – Bristol Myers Squibb Adds Premier Radiopharmaceutical Platform with Acquisition of RayzeBio (bms.com)

Update – 31 May 2023 – RYZ101 Phase 3 ACTION‑1 Trial

RayzeBio dosed the first patient in the Phase 3 ACTION‑1 trial of RYZ101 (Actinium‑225 DOTATATE) for SSTR+ GEP‑NETs that have progressed after Lutetium‑177 SSA therapy.

Trial design (NCT05477576):

Global, 210 patients
Randomised 1:1
- RYZ101 vs investigator’s choice (everolimus, sunitinib,, or high‑dose SSA)
Primary endpoint: Progression‑Free Survival (PFS)
Crossover allowed from SOC → RYZ101 at progression

RYZ101 was well tolerated in Phase 1b, and updated efficacy data were expected as enrolment progressed.

Status:

The RYZ101 clinical trial programme has now ended.

Clarifying the Relationship Between RYZ101 and RYZ401

Although both drugs are targeted alpha‑emitter radiopharmaceuticals developed by RayzeBio/BMS, they are designed for completely different patient groups.

RYZ101 – For PRRT‑Pretreated Patients Only

Eligibility requires:

SSTR‑positive GEP‑NETs, and
prior Lu‑177 PRRT, and
disease progression after Lu‑177

Prior PRRT is mandatory.

RYZ401 – For PRRT‑Naïve Patients Only

Eligibility requires:

SSTR‑expressing solid tumours (NETs, meningioma, others), and
no prior PRRT of any kind

Prior PRRT is an exclusion criterion.

Background Information

What is Alpha‑Emitter PRRT?

Alpha‑emitters (e.g., ²¹²Pb, ²²⁵Ac) deliver:

much higher Linear Energy Transfer (LET) → more tumour cell kill
shorter path length → less damage to surrounding tissue

This is why alpha‑PRRT is considered a major next step in radioligand therapy.

What is RYZ101?

RYZ101 is Actinium‑225 DOTATATE, designed for SSTR2‑expressing tumours. It has been evaluated in:

GEP‑NETs after Lu‑177 PRRT
A planned study in extensive‑stage small cell lung cancer (ES‑SCLC) (NCT05595460)

What is RYZ401?

RYZ401 is a Actinium‑225 DOTATATE in early‑phase development. It is being tested in:

NETs
Meningioma
Other SSTR‑positive solid tumours

It is specifically for PRRT‑naïve patients.

Sources Used

1. RayzeBio news – click here
2. RayzeBio website – click here
3. The clinical trial document for the Action-1 trial: NCT05477576 (click here) (As at 8th Jan 2022, only 7 trial centres in USA are listed)
4. The clinical trial document for the Small Cell Lung Cancer trial NCT05595460 – click here. This is a Phase 1b Single Arm, Open-label Trial of RYZ101 in Combination With Carboplatin + Etoposide + Atezolizumab in Subjects With Somatostatin Receptor Expressing (SSTR+) Extensive Stage Small Cell Lung Cancer (ES-SCLC).
5. The clinical trial document for the solid tumour trial of RYZ401 NCT07165132 – click here

Read my general Alpha-emitter PRRT blog post here or click on the picture below:

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.

Click here to enter Ronny’s Clinical Trials Archive

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

Finally

Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET