Clinical trial NCT07020117: A Phase 1b Study of [225Ac]Ac-AKY-1189 in Patients With Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Urothelial Carcinoma Bladder
Triple Negative Breast Cancer (TNBC)
Hormone Receptor Positive Breast Adenocarcinoma
Non Small Cell Lung Cancer
Cervical Adenocarcinoma
Colorectal Adenocarcinoma
Head and Neck Cancer
Lead sponsor: Aktis Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2025-06-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a first-in-human Phase 1b, 2-part, multicenter open-label clinical study to evaluate safety and efficacy of a Nectin-4 radiopharmaceutical (\[225Ac\]Ac-AKY-1189) in patients with locally advanced or metastatic solid tumors and to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended Part 2 dose.

Detailed description: This study consists for two parts (Part 1 and 2).

Part 1 is the dose escalation portion of the study, which will investigate ascending doses of \[225Ac\]Ac-AKY-1189 (up to 6 cycles) in patients with locally advanced or metastatic urothelial cancer. The aim of Part 1 is to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended Part 2 dose.

Part 2 will be the dose expansion portion of the study and will enroll locally advanced or metastatic solid tumor patients who are identified as Nectin-4 positive by \[64Cu\] Cu-AKY-1189. Part 2 aims to further assess the efficacy on \[225Ac\]Ac-AKY-1189 at the RP2D in 3 different cohorts of patients.

Eligibility 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 radiopharmaceutial
* 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

Primary outcomes:
measure: Part 1: Number of Patients with Dose-Limiting Toxicities
timeFrame: From enrollment to the end of Cycle 1 (each cycle is 28 days)
measure: Part 1: Occurence of Adverse Events by Severity
timeFrame: Up to the End of Treatment (30 days after the last dose)
measure: Part 2: Objective Response Rate (ORR)
timeFrame: Up to 30 days following last administration
Secondary outcomes:
measure: Part 1: Objective Response Rate (ORR)
timeFrame: Up to 30 days following last adminstration
measure: Part 2: Occurence of Adverse Events by Severity
timeFrame: Up to End of Treatment (30 days after the last dose)
measure: Part 1 and 2: Duration of Response (DOR)
timeFrame: Up to 5 years after first administration
measure: Part 1 and 2: Progression-Free Survival (PFS)
timeFrame: Up to 5 years after first administration
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: BAMF Health
state: Michigan
Study officials:
References: