Cervical Adenocarcinoma, Colorectal Adenocarcinoma, Head and Neck Cancer, Hormone Receptor Positive Breast Adenocarcinoma, Non Small Cell Lung Cancer, Triple Negative Breast Cancer (TNBC), Urothelial Carcinoma Bladder
Conditions
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 Phase 2 dose.
Detailed description
This study consists of 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 solid tumors. The aim of Part 1 is to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended Phase 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 of \[225Ac\]Ac-AKY-1189 at the RP2D in 3 different cohorts of patients.
Interventions
DRUG[225Ac]Ac-AKY-1189 (therapeutic)
\[225Ac\]Ac-AKY-1189 Injection
DRUG[64Cu]Cu-AKY-1189 (imaging)
\[64Cu\]Cu-AKY-1189 Injection
Sponsors
Aktis Oncology, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Patients with Dose-Limiting Toxicities | From enrollment to the end of Cycle 1 (each cycle is 28 days) | • Dose-limiting toxicities (DLTs) is defined as any predefined AE occurring during the DLT observation period, except those that are clearly and incontrovertibly due to extraneous circumstances. The number of patients who experience a DLT in Part 1, will be reported by dose level. |
| Part 1: Occurence of Adverse Events by Severity | Up to the End of Treatment (30 days after the last dose) | • An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of patients experiencing an AE in Part 1 will be reported. |
| Part 2: Objective Response Rate (ORR) | Up to 30 days following last administration | • Objective response rate is defined as the percentage of patients who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator based on RECIST 1.1, by tumor types. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Objective Response Rate (ORR) | Up to 30 days following last adminstration | • Objective response rate is defined as the percentage of patients who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator based on RECIST 1.1, by dose level. |
| Part 2: Occurence of Adverse Events by Severity | Up to End of Treatment (30 days after the last dose) | • An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of patients experiencing an AE in Part 2 will be reported. |
| Part 1 and 2: Duration of Response (DOR) | Up to 5 years after first administration | • Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. |
| Part 1 and 2: Progression-Free Survival (PFS) | Up to 5 years after first administration | • PFS is defined as the time from treatment initiation to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first. |
Countries
United States
Contacts
CONTACTJanet Horton, MD
Outcome results
None listed