Zelenectide Pevedotin
A small two-ring peptide that carries a chemotherapy toxin to Nectin-4 on cancer cells, in late-stage trials for urothelial cancer
Zelenectide pevedotin, first called BT8009, joins a small bicyclic peptide that grips the tumour protein Nectin-4 to monomethyl auristatin E, the same cell-killing toxin used in the approved antibody conjugate enfortumab vedotin. Being far smaller than an antibody, it moved quickly through tissue and left the body through the kidneys in animal studies. In its first trial in people, 49 patients with advanced cancers, most with bladder cancer, received it by vein; 38% of those with urothelial cancer whose response could be judged responded. It is in phase 2 and 2/3 trials and is not approved.
Used in human trials: 5.0 mg/m², Once weekly, Intravenous (Study: recommended phase 2 dose, weekly) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Enfortumab vedotin, an antibody against Nectin-4 that carries the toxin MMAE, is approved for urothelial carcinoma, a cancer whose cells carry high levels of Nectin-4. It works well there, but the developers of zelenectide point out that little is known of its effect in other Nectin-4 cancers and that its side effects often make patients stop treatment. Bicycle Therapeutics set out to deliver the same toxin on a much smaller carrier.
A Bicycle is a short peptide closed into two rings, a shape that holds it rigid for binding. The company found a Nectin-4 binder by phage display. Its first form fell apart quickly in plasma and dissolved poorly; swapping in non-natural amino acids fixed both problems, and the optimised peptide was joined through a cleavable linker to MMAE. The result, BT8009, is the drug now called zelenectide pevedotin. Its structure is complex enough that a 2026 paper was devoted to working it out by NMR.
In rodents and monkeys it behaved as designed. It moved quickly from blood into tumour, was cleared by the kidneys with a half-life of one to two hours, and in several mouse tumour models worked as well as or better than an analogue of enfortumab vedotin, and it was well tolerated in safety studies. The developers argue that fast tumour penetration combined with short time in the blood may lower exposure of normal tissue to the toxin compared with an antibody conjugate.
The first human trial, Duravelo-1, tested doses from 2.5 to 10 mg per square metre of body surface in 49 heavily pretreated patients. Nausea was the most common side effect, in about half, which the authors put down to the lack of anti-sickness medicine during the first cycle; fatigue, nerve damage, low neutrophil counts and skin reactions followed. Severe events were mostly neutropenia. A quarter of all evaluable patients and 38% of those with urothelial cancer had their tumours shrink, and responses lasted a median of 11 months. Two schedules were chosen for further study: 5 mg/m² weekly, and 7.5 mg/m² on days 1 and 8 of a three-week cycle.
Those results led to Duravelo-2, registered as a randomised phase 2/3 trial in urothelial cancer. In patients not previously treated it combines zelenectide with pembrolizumab and compares that with platinum chemotherapy; a second cohort tests it alone in previously treated patients. A 2025 review questioned this design, calling its control arms outdated and noting that no arm compares zelenectide directly with enfortumab vedotin. Further phase 2 trials are testing it in breast cancer and in lung cancers whose NECTIN4 gene is amplified.
It is not approved anywhere. A 2026 paper reports US fast-track designation for bladder, breast and lung cancers, which speeds review but says nothing about whether the drug works. It is a hospital-only cancer drug given by infusion, not something that exists outside clinical trials.
Mechanism of Action
The peptide finds the cell; the toxin does the killing. Its developers designed the small carrier to change where and for how long the toxin is present, compared with an antibody carrying the same payload.
Binding Nectin-4
The bicyclic peptide, found by phage display and stabilised with non-natural amino acids, binds Nectin-4 selectively (2022 discovery paper).
Releasing MMAE
A valine-citrulline linker is cut by enzymes in the tumour, freeing MMAE, which blocks microtubules and stops cell division (2025 bioanalysis and 2026 structure papers).
Tumour penetration and fast clearance
As a small hydrophilic molecule it diffuses rapidly into tissue and is eliminated by the kidneys, with a one-to-two-hour half-life in rats and monkeys (2022 preclinical study).
Independent of internalisation
A 2025 review describes the design as able to work without the cell taking the conjugate inside, unlike antibody conjugates, which must be internalised.
Published Research
These are the studies of zelenectide pevedotin read from their PubMed abstracts on October 29, 2026: one trial in patients, one assay validated on patients' plasma, three reviews, one structure paper and three preclinical studies. Two reviews and one mouse study do not name it in their titles; they are carded because their abstracts name it as the drug discussed or given.
First-in-human dose escalation (Duravelo-1)
Forty-nine adults with advanced Nectin-4-associated cancers, 25 with urothelial cancer and a median of three earlier treatments, received 2.5-10 mg/m² by vein on weekly, days 1 and 8, or two-weekly schedules. Common side effects were nausea (49%), fatigue (39%), neuropathy (33%), neutropenia (22%; 16% severe) and skin reactions (22%). The maximum tolerated dose was 7.5 mg/m² every two weeks. Responses: 24% overall, 38% in urothelial cancer, lasting a median 11.1 months.
Measuring the drug in patients' plasma
A liquid chromatography-mass spectrometry method quantified intact zelenectide pevedotin from 5 to 2,500 ng/mL in 50 µL of plasma, met FDA and EMA validation criteria, and was used on more than 3,000 samples from the phase 1/2 trial. The paper describes the valine-citrulline cleavable linker.
Promise and trial-design concerns
A review of its preclinical rationale, pharmacokinetics, safety and efficacy against enfortumab vedotin finds the early profile promising, but criticises the Duravelo-2 design for outdated control arms and no direct comparison with enfortumab vedotin, which could delay approval.
Early-phase urothelial trials, 2024-2025
An update on early-phase trials in urothelial carcinoma lists bicycle toxin conjugates such as zelenectide pevedotin among the novel agents with promising early results.
Drugs aimed at Nectin-4 and related targets
A review of conjugates against cadherins, claudins and nectins notes that enfortumab vedotin is approved for urothelial cancer and lists zelenectide pevedotin among the Nectin-4 agents in randomised late-stage trials.
Solving the structure by NMR
Chemists describe a step-by-step NMR strategy for confirming the structure of the Bicycle, spacer, cleavable linker and MMAE; the paper notes fast-track designation for bladder, breast and lung cancers.
Discovery of BT8009
A Nectin-4 binder found by phage display was unstable in plasma and poorly soluble; non-natural amino acids gave high affinity and stability, and joining it to MMAE through a cleavable linker gave BT8009, which was potent against tumours in rodents.
Preclinical package
In mouse tumour models across several cancer types it matched or beat an enfortumab vedotin analogue, was well tolerated in safety studies, diffused rapidly into tumours and was cleared by the kidneys with a half-life of 1-2 hours in rats and monkeys.
Comparator for a newer conjugate
In a study of a rival Nectin-4 conjugate, BT8009 bound Nectin-4 with a KD of about 0.32 µM and, at 0.12 µmol/kg, inhibited prostate-cancer xenografts by 87.6%; at 0.36 µmol/kg it inhibited gastric-cancer xenografts by 72.7% in nude mice.
Dosing Data
Zelenectide pevedotin is not approved and has no label. The rows below are the schedules its first trial chose for further study, stated in the published abstract. It is an intravenous cancer drug given in hospital with blood counts monitored; doses are calculated from body surface area.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no regulator's label that says in what form Zelenectide Pevedotin is supplied. It is prepared and given by clinical staff, not bought and mixed at home: the next part says where.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Zelenectide Pevedotin is prepared and given by clinical staff, by a cancer team in hospital.
In the carded trial it was given into a vein on set days of each cycle to adults with advanced cancers.
Source: PMID 41197088 (a study carded under Research below).
Storage before and after mixing
Unknown: no label on file says how Zelenectide Pevedotin is stored. It is kept and prepared by the hospital or clinic that gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intravenous (Once weekly; Study: recommended phase 2 dose, weekly).
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of 1-2 hours in rats and monkeys; no human figure in the abstracts read. After about five half-lives almost none is left.
How long the doses were given: Study: recommended phase 2 dose, weekly: 28-day cycles; Study: recommended phase 2 dose, days 1 and 8: 21-day cycles; Study: maximum tolerated dose: 28-day cycles.
When effects appear: unknown; no source on this page gives a time to effect for Zelenectide Pevedotin. Results reported in the studies are under Published Research.
Source: half-life: PMID 36112771; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Nausea in 49% (severe in 2%), attributed to the lack of anti-sickness prophylaxis in the first cycle; Fatigue in 39% (severe in 6%); Peripheral neuropathy in 33% (severe in 2%), a known effect of MMAE; Neutropenia in 22%, severe in 16%; Skin reactions in 22% (severe in 2%). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Zelenectide Pevedotin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the first-in-human trial (PMID 41197088)”).
Interactions
Unknown: a PubMed search for human interaction studies of Zelenectide Pevedotin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Zelenectide Pevedotin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved: Drugs@FDA and the EMA medicines list hold no record (searched October 28, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the first-in-human trial (PMID 41197088).
Contraindications & Cautions
No label exists. These cautions come from the trial and its toxin.
Legal Status
An investigational cancer drug in phase 2 and 2/3 trials.
Frequently Asked Questions
?What is zelenectide pevedotin?
An investigational cancer drug: a small bicyclic peptide that binds Nectin-4 on tumour cells, joined to the toxin MMAE. It was developed as BT8009 by Bicycle Therapeutics.
?How is it different from enfortumab vedotin?
Both deliver MMAE to Nectin-4. Enfortumab vedotin uses an antibody, which is large and stays in the blood for days; zelenectide uses a much smaller peptide that entered tumours quickly and was cleared within hours in animals. No trial has compared the two directly.
?Does it work?
In its first trial, tumours shrank in 38% of evaluable patients with urothelial cancer, and responses lasted a median 11 months. Larger randomised trials are under way and have not reported.
?What are the side effects?
Nausea, fatigue, nerve damage, low white-cell counts and skin reactions were the most common in the first trial; severe neutropenia affected 16%.
?Is it approved?
No. It is available only in clinical trials, as of October 2026.
References
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT04561362 (phase 1/2, Duravelo-1), NCT06225596 (phase 2, Duravelo-2, urothelial cancer), NCT06840483 (phase 2, breast cancer) and NCT06933329 (phase 2, NECTIN4-amplified lung cancer), all active, not recruiting.
- [other] ChEMBL CHEMBL5314903, zelenectide pevedotin (synonyms include BT8009): maximum clinical phase 2 in the ChEMBL molecule record, read October 2, 2026 (the Registry's ChEMBL harvest). https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL5314903/
- [clinical-trial] Baldini C, et al. "First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation." J Clin Oncol, 2025;43(35):3728-3738. PMID: 41197088.
- [pubmed] Tweed JA, et al. "The validation and clinical bioanalysis of the Bicycle® Toxin Conjugate zelenectide pevedotin in human plasma." Bioanalysis, 2025;17(3):177-185. PMID: 39829185.
- [review] Cigliola A, et al. "Zelenectide pevedotin (BT-8009): a bicyclic peptide toxin conjugate targeting nectin-4 for the treatment of bladder cancer." Expert Opin Investig Drugs, 2025;34(5):371-378. PMID: 40401457.
- [review] Lee YHA, et al. "The future of urothelial carcinoma: a 2024-2025 update of early-phase trials of novel therapeutic agents." Curr Opin Urol, 2026;36(3):244-249. PMID: 41861349.
- [review] Katoh M, et al. "Antibody-drug conjugates targeting the cadherin, claudin and nectin families of adhesion molecules." Front Mol Med, 2025;5:1661016. PMID: 41164107.
- [pubmed] Jonasson K, et al. "From Cloudy to Clear: A Strategy to Resolve the Complex Structural Elucidation of Bicycle Drug Conjugate Zelenectide Pevedotin by NMR." Bioconjug Chem, 2026;37(2):293-302. PMID: 41553133.
- [pubmed] Mudd GE, et al. "Discovery of BT8009: A Nectin-4 Targeting Bicycle Toxin Conjugate for the Treatment of Cancer." J Med Chem, 2022;65(21):14337-14347. PMID: 36204777.
- [pubmed] Rigby M, et al. "BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors." Mol Cancer Ther, 2022;21(12):1747-1756. PMID: 36112771.
- [pubmed] Gu JN, et al. "Design, synthesis and antitumor evaluation of a novel nectin-4 targeting bicyclic toxin conjugate." Bioorg Med Chem Lett, 2025;127:130306. PMID: 40505992.
- [pubmed] Krönke T, et al. ""Precision on Two Wheels"─Structural Refinement of (64)Cu- and (68)Ga-Labeled Bicyclic Peptides Targeting Nectin-4 for Improved Tumor Imaging: From Preclinical Development to First-in-Human Application." J Med Chem, 2025;68(20):21962-21987. PMID: 41081542.
- [registry] ClinicalTrials.gov API v2, read October 29, 2026: NCT06225596 (Duravelo-2; official title 'A Randomized Open-Label Phase 2/3 Study of BT8009 as Monotherapy or in Combination' in urothelial cancer; 375 participants planned; active, not recruiting; cohort 1 with pembrolizumab against platinum-based chemotherapy with or without avelumab maintenance, cohort 2 alone) and NCT04561362 (Duravelo-1, phase 1/2, 329 planned, active, not recruiting; arms include a renal-insufficiency cohort, Part C). https://clinicaltrials.gov/study/NCT06225596
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Trial status and design come from ClinicalTrials.gov, read October 29, 2026; regulatory status from Drugs@FDA and the EMA medicines list, searched October 28, 2026. A study of imaging tracers derived from the same peptide is listed under References with a reason. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.