Nectin-4 targeted alpha radiotherapy [225Ac]Ac-AKY-1189 for advanced solid tumors
NECTINIUM-2: A Phase 1b, 2 Part, Multicenter, Single Arm, Open Label Study to Evaluate the Safety and Efficacy of a Nectin-4 Radiopharmaceutical ([225Ac]Ac-AKY-1189) in Patients With Previously Treated Locally Advanced or Metastatic Solid Tumors
This trial will try a Nectin‑4–targeted radioactive drug called [225Ac]Ac‑AKY‑1189 in adults with locally advanced or metastatic solid tumors, including certain bladder, breast, lung, and cervical cancers.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 150 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Aktis Oncology, Inc. Industry-sponsored |
| Drugs / interventions | enfortumab, chemotherapy, immunotherapy |
| Locations | 9 sites (Duarte, California and 8 other locations) |
| Trial ID | NCT07020117 on ClinicalTrials.gov |
What this trial studies
This first‑in‑human, multicenter Phase 1b trial has two parts: a dose‑escalation phase (Part 1) to find the maximum tolerated or administered dose and a dose‑expansion phase (Part 2) to study activity at the recommended Phase 2 dose. Part 1 will give ascending doses of [225Ac]Ac‑AKY‑1189 for up to six cycles to patients with locally advanced or metastatic solid tumors to define tolerability and dose limits. Part 2 will use the imaging agent [64Cu]Cu‑AKY‑1189 to identify Nectin‑4 positive tumors and then enroll those patients into three expansion cohorts to gather efficacy and safety data at the selected dose. The study is open‑label and includes serial imaging, safety labs, and tumor assessments by RECIST v1.1.
Who should consider this trial
Good fit: Ideal candidates are adults with histologically confirmed locally advanced or metastatic solid tumors that are measurable, have ECOG 0–1 and adequate organ function, have progressed on prior therapy, and (for expansion) test Nectin‑4 positive by [64Cu]Cu‑AKY‑1189 imaging.
Not a fit: Patients who previously received a therapeutic radiopharmaceutical, prior Nectin‑4–directed therapy (except enfortumab vedotin), have poor performance status, uncontrolled medical conditions, recent disqualifying therapies, or are Nectin‑4 negative are less likely to benefit.
Why it matters
Potential benefit: If successful, it could offer a new targeted radiopharmaceutical that shrinks tumors in patients with Nectin‑4 positive advanced cancers.
How similar studies have performed: Nectin‑4 is a validated target for antibody–drug conjugates like enfortumab vedotin, but Nectin‑4–targeted alpha‑emitting radiopharmaceuticals are novel and have limited prior human data, so this approach is promising but early.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Histologic or cytologic confirmation of locally advance or metastatic disease * Radiologic confirmation on CT of at least one measurable tumor lesion per RECIST v1.1 * ECOG Performance Status of 0 or 1 * Adequate end-organ function * Ability to give informed consent and comply with study requirements * Patients with CNS metastases are eligible if they have received therapy and are neurologically stable, asymptomatic and not receiving corticosteroids * Documented disease progression on prior line of therapy for metastatic disease Exclusion Criteria: * Prior treatment with a therapeutic radiopharmaceutical * Prior treatment with a Nectin-4 targeted therapy, except enfortumab vedotin * Received an investigational agent within the previous 28days * Prior treatment with a cytotoxic chemotherapy, targeted therapy, biologic agent, immunotherapy or external-beam radiotherapy in the 3 weeks prior to study treatment * Concurrent serious medical condition that would impair study participation or impact the assessment of treatment related toxicity
Where this trial is running
Duarte, California and 8 other locations
- City of Hope — Duarte, California, United States (Recruiting)
- Hoag Memorial Hospital Presbyterian — Irvine, California, United States (Recruiting)
- Biogenix Molecular, LLC — Miami, Florida, United States (Recruiting)
- University of Iowa — Iowa City, Iowa, United States (Recruiting)
- United Theranostics — Glen Burnie, Maryland, United States (Recruiting)
- BAMF Health — Grand Rapids, Michigan, United States (Recruiting)
- Icahn School of Medicine at Mt. Sinai — New York, New York, United States (Recruiting)
- Upmc — Pittsburgh, Pennsylvania, United States (Recruiting)
- MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Study coordinator: Janet Horton, MD
- Email: AKY-1189-01inquiries@aktisoncology.com
- Phone: 978-208-3986
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.