A Study of [225Ac]Ac-AKY-2519 in Patients With Metastatic Castration-Resistant Prostate Cancer

Phase 1RecruitingNCT07581184

Aktis Oncology, Inc.138 enrolled

Overview

This is a Phase 1b, multi-center, open-label study to evaluate the safety, tolerability, dosimetry, and pharmacokinetics (PK) of \[64Cu\]Cu-AKY-2519 and/or \[225Ac\]Ac-AKY-2519, as well as the preliminary anti-tumor activity of \[225Ac\]Ac-AKY-2519 in participants with metastatic castration-resistant prostate cancer (mCRPC) with and without prior exposure to 177Lu-PSMA-617 (PLUVICTO™).

This Phase 1b study consists of a dose escalation portion and a backfill portion. The dose escalation portion will investigate ascending doses of \[225Ac\]Ac-AKY-2519 across two cohorts enrolling in parallel: * Cohort A: participants with metastatic castration-resistant prostate cancer (mCRPC) with NO prior exposure to 177Lu-PSMA-617 (PLUVICTO™) and * Cohort B: participants with metastatic castration-resistant prostate cancer (mCRPC) with prior exposure to 177Lu-PSMA-617 (PLUVICTO™) The backfill portion may enrich in two select dose levels from each cohort (Cohort A: mCRPC 177Lu-PSMA-617 (PLUVICTO™)-naïve; Cohort B: mCRPC 177Lu-PSMA-617 (PLUVICTO™)-experienced) to gather further information on the safety and efficacy and to determine the recommended phase 2 dose (RP2D) for each cohort.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

138

Conditions

Castration Resistant Metastatic Prostate Cancer

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Histologic or cytologic confirmation of prostatic adenocarcinoma * 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 * Castrate levels of serum testosterone (\< 50 ng/dL) * Documented disease progression on most recent prior line of therapy, either by PSA or imaging-based progression * Cohort B: Received 2 or more prior doses of 177Lu-PSMA-617 (PLUVICTO) Exclusion Criteria: * Prior treatment with more than 2 Androgen receptor pathway inhibitors (ARPIs) and/or more than 1 taxane-based therapy in the mCRPC setting * Prior treatment with a targeted radiotherapy o Exception: Cohort B is required to have had at least 2 prior doses of 177Lu-PSMA-617 (PLUVICTO) * Prior treatment with a B7-H3 targeted therapy * Received an investigational agent within the previous 28 days * Impaired cardiac function or clinically significant cardiac disease * Concurrent serious medical condition that would impair study participation or impact the assessment of treatment related toxicity

Outcomes

Primary Outcomes

Occurrence of adverse events by severity and occurrence of serious adverse events (SAEs) in participants who received [225Ac]Ac-AKY-2519

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 and the number of patients experiencing an SAE will be reported. Up to 30 days following last administration of \[225Ac\]Ac-AKY-2519

Time frame: Up to 30 days following last administration of [225Ac]Ac-AKY-2519

Occurrence of dose-limiting toxicity (DLT) in mCRPC participants with and without prior 177Lu-PSMA-617 exposure

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 will be reported separately for each cohort and by dose level within each cohort.

Time frame: From first administration of [225Ac]Ac-AKY-2519 to the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes

Occurrence of adverse events by severity and occurrence of serious adverse events (SAEs) in participants who received [64Cu]Cu-AKY-2519

Time frame: Up to 30 days following last administration of [64Cu]Cu-AKY-2519

Objective Response Rate (ORR)

ORR 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 PCWG3-modified RECIST v1.1.

Time frame: Up to 30 days following last administration of [225Ac]Ac-AKY-2519

Duration of Response (DoR)

Duration of Response (DoR) is 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.

Time frame: Up to 5 years after first administration

Progression-Free Survival (PFS)

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.

Time frame: Up to 5 years after first administration

Prostate Specific Antigen (PSA) >= 50% Response Rate (PSA50)

Will assess PSA decline of \>= 50% from baseline (PSA50), using the Prostate Cancer Working Group 3 (PCWG3) criteria.

Time frame: Up to 30 days following last administration of [225Ac]Ac-AKY-2519

Prostate Specific Antigen (PSA) >= 90% Response Rate (PSA90)

Will assess PSA decline of \>= 90% from baseline (PSA90), using the Prostate Cancer Working Group 3 (PCWG3) criteria.

Time frame: Up to 30 days following last administration of [225Ac]Ac-AKY-2519

A Study of [225Ac]Ac-AKY-2519 in Patients With Metastatic Castration-Resistant Prostate Cancer

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts