RYZ101 (225Ac-DOTATATE), an alpha radioligand, met its Phase 3 ACTION-1 endpoint in GEP-NETs. How radioactive peptides work, Lutathera vs Pluvicto, what's known, and what isn't.
Educational only, not medical advice. PeptIQ never gives dosing advice. The drugs in this guide are prescription nuclear-medicine therapies given only in hospitals and specialized centers. If you or someone you love has cancer, talk to an oncologist.
You may have seen the headline: "A radioactive peptide that targets cancer cells and delivers radiation to destroy them has just succeeded in a Phase 3 trial." It's real, and it matters. Here's what happened, without the hype.
Phase 3 win for an alpha-emitting radiopharmaceutical, in any cancer
of GEP-NETs express SSTR2, the receptor RYZ101 targets
people diagnosed with GEP-NETs in the US each year
On October 12, 2026, Bristol Myers Squibb announced that RYZ101 (actinium-225 DOTATATE) met the primary endpoint of the Phase 3 ACTION-1 trial (NCT05477576) at a planned interim analysis (BMS press release). RayzeBio, a BMS company, ran the trial.
ACTION-1 · Phase 3 · NCT05477576
Alpha-emitting radioligand given IV in a nuclear-medicine setting
High-dose or high-frequency SSAs, everolimus, or sunitinib
Statistically significant, clinically meaningful PFS gain at interim analysis
Median PFS, hazard ratio, overall survival, detailed safety
“These are the first results from a Phase 3 trial of an alpha-isotope based targeted RPT (225Ac) in any indication.”
Why there's no results chart here: BMS hasn't published the median PFS, hazard ratio or side-effect rates. It says detailed results will be presented at a future medical meeting. We won't invent numbers, and you should be skeptical of anyone quoting them before then.
The approach is called peptide receptor radionuclide therapy (PRRT). It's part of a broader class called radioligand or radiopharmaceutical therapy, and it has three parts:
How it works
Actinium-225 emits short-range, high-energy alpha particles that can break both strands of DNA.
A molecular cage that holds the radioactive metal tightly so it travels with the peptide.
A somatostatin look-alike that homes in on SSTR2 receptors on neuroendocrine tumor cells.
Lutathera, the approved PRRT for GEP-NETs, uses lutetium-177, a beta emitter. RYZ101 keeps the same targeting peptide and swaps in actinium-225, an alpha emitter. BMS says alpha particles are high-energy and short-range and can cause double-stranded DNA breaks, "potentially resulting in higher chance of cancer cell death."
That's why ACTION-1 enrolled people who had already progressed on lutetium-177. The trial's principal investigator, Simron Singh, MD, of Sunnybrook's Odette Cancer Centre, put the gap plainly (BMS):
“Until now there has been no randomized Phase 3 evidence to guide it.”
In an earlier Phase 1b trial of 17 previously Lu-177-treated patients, BMS reports RYZ101 was well tolerated, with no treatment-related serious adverse events.
| Lutathera | Pluvicto | RYZ101 | |
|---|---|---|---|
| Targeting part | DOTATATE (peptide) | PSMA-binding small molecule | DOTATATE (peptide) |
| Isotope | Lutetium-177 (beta) | Lutetium-177 (beta) | Actinium-225 (alpha) |
| Cancer | SSTR+ GEP-NETs | PSMA+ metastatic castration-resistant prostate cancer | SSTR+ GEP-NETs after Lu-177 |
| FDA status | Approved Jan 26, 2018 (adults); ages 12+ added Apr 2024 | Approved Mar 23, 2022 | Investigational; orphan drug designation Aug 2026 |
Sources: Lutathera FDA approval package, FDA orphan drug database, Pluvicto FDA approval package, Novartis, BMS.
Timeline
FDA approves lutetium-177 dotatate for adults with SSTR+ GEP-NETs.
FDA approves a PSMA-targeted lutetium-177 therapy for metastatic castration-resistant prostate cancer.
Approval extended to patients 12 and older.
FDA grants Orphan Drug Designation for GEP-NETs.
First Phase 3 win for an alpha-emitting targeted radiopharmaceutical.
No. Insulin, GLP-1 drugs, BPC-157 and DOTATATE are all called "peptides," but they have little else in common.
RYZ101, Lutathera and Pluvicto are radioactive prescription drugs. They're made under strict controls and shipped on tight timelines because the isotope decays. Nuclear-medicine teams give them intravenously in licensed facilities with radiation-safety protocols. Patients are first selected with specialized imaging that confirms their tumor carries the target.
There's no "research peptide" version of this. Treat anything sold online as one as a scam or a danger. If you have a neuroendocrine tumor or prostate cancer, ask your oncologist whether radioligand therapy or a clinical trial is right for you. You can search open trials at ClinicalTrials.gov.
ACTION-1 is the first Phase 3 success for an alpha-emitting targeted radiopharmaceutical. It's a meaningful step for people with advanced GEP-NETs and for peptide-guided radiation as a field. The detailed data and the FDA's review are still ahead. For now, the right next step is a conversation with an oncologist, not a search for something to buy.
PeptIQ tracks peptide research, from approved medicines to early trials, so you can walk into your clinician's office informed. Download the PeptIQ app to follow the research and keep your health records in one place.
RYZ101 is an investigational radiopharmaceutical from RayzeBio, a Bristol Myers Squibb company. It combines DOTATATE, a peptide that binds somatostatin receptors on neuroendocrine tumor cells, with actinium-225, an alpha-emitting radioactive isotope.
According to Bristol Myers Squibb (Oct 12, 2026), the randomized Phase 3 ACTION-1 trial (NCT05477576) met its primary endpoint at a planned interim analysis. RYZ101 produced a statistically significant and clinically meaningful improvement in progression-free survival versus investigator's choice of standard care in SSTR-positive GEP-NETs that progressed after lutetium-177 therapy. Detailed figures have not been released.
No. RYZ101 is investigational. The FDA granted it Orphan Drug Designation for GEP-NETs in August 2026, and Bristol Myers Squibb says it plans to discuss a regulatory submission with the FDA.
Both are FDA-approved lutetium-177 radioligand therapies. Lutathera (approved January 2018) uses the peptide DOTATATE to target somatostatin receptors in GEP-NETs. Pluvicto (approved March 2022) targets PSMA in metastatic castration-resistant prostate cancer. RYZ101 uses the same targeting peptide as Lutathera but carries the alpha emitter actinium-225 instead of lutetium-177.
Peptide receptor radionuclide therapy (PRRT) uses a peptide that binds receptors on tumor cells to deliver a radioactive isotope directly to the cancer. Lutathera is an approved example. It is part of the broader class of radioligand or radiopharmaceutical therapies.
No. These are radioactive prescription drugs prepared under strict controls and given intravenously by nuclear-medicine teams in licensed facilities. Anything sold online claiming to be one should be treated as a scam or a danger. Ask an oncologist whether radioligand therapy or a clinical trial fits your situation.
Eligibility depends on cancer type and on specialized imaging that confirms the tumor carries the target receptor, such as somatostatin receptors for Lutathera or PSMA for Pluvicto. Only an oncologist or nuclear-medicine physician can decide.
