An Open-label Dosimetry, Tolerability and Safety Study of lutetium (177Lu) vipivotide tetraxetan in Patients with Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Moderately and Severely Impaired and with Normal Renal Function

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Apr 2024 → ongoing

Decision date (initial)

2023-11-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-503925-20-00

ClinicalTrials.gov

NCT06004661

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To assess potential impact of moderate and severe renal impairment on the dosimetry, biodistribution (PK), safety and tolerability of AAA617

Secondary objectives 5

1. Key secondary: To evaluate the effect of AAA617 on the QTc interval including Concentration/QT assessment.
2. To assess the safety of AAA617
3. To evaluate the overall response rate (ORR) and disease control rate (DCR) for AAA617.
4. To evaluate the Prostate Specific Antigen 50 (PSA50) response
5. To evaluate potential impact of moderate and severe renal impairment on AAA617 urine PK

Conditions and MedDRA coding

Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) with moderate and severe renal impairment and with normal renal function.

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002577-PIP01-19, EMEA-002419-PIP02-18

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
2. 68Ga-PSMA-11 Positron emission tomography (PET)/CT scan positive, and eligible as determined by the sponsor’s central reader
3. A castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
4. Documented progressive mCRPC will be based on at least 1 of the following criteria: • Serum/plasma Prostate-Specific Antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. • Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. • Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al 2016).
5. Documented stable chronic renal disease without evidence of further deterioration in renal function (stable chronic renal disease is defined as no significant change in renal function, within 4 weeks prior to study entry as documented by ≤ 20% difference between two separate eGFR measurements calculated with the MDRD equation. In addition, all eGFR values available within 3 months prior to study entry should be classified in the same eGFR category as the calculated eGFR at screening).
6. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD) equation (at first screening assessment): • Normal renal function: participants with eGFR ≥ 90 mL/min/1.73m2 • Moderate renal impairment: participants with eGFR ≥30 to ≤59 mL/min/1.73m2 • Severe renal impairment: participants with eGFR ≥15 to ≤29 mL/min/1.73m2

Exclusion criteria 5

1. Previous treatment with PSMA-targeted radioligand therapy.
2. Previous treatment with any of the following within 6 months of enrollment confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
3. Use of agents known to prolong the QT interval from start of screening to end of Cycle 1, unless they can be permanently discontinued for the duration of study.
4. Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters. Participants with postrenal impairment, like obstructions, retroperitoneal fibrosis (eg after prostatectomy) must be excluded or first resolved to ≤ Grade 1
5. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study such as: • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker. • History of familial long QT syndrome or known family history of Torsades de Pointe. • Resting heart rate (12 lead ECG) <60 bpm

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Absorbed radiation dose in kidney and selected organs.
2. Concentrations of AAA617 in blood over time and derived pharmacokinetic (PK) parameters from blood radioactivity data.
3. Change from baseline in eGFR using the by-timepoint analysis.
4. Tolerability: dose interruptions, reductions and dose intensity.

Secondary endpoints 6

1. Change from baseline in QT interval corrected by Fridericia’s formula (QTcF) interval (ΔQTcF) using the by-timepoint analysis.
2. Relationship between drug concentrations and QTcF.
3. Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), changes in laboratory values, vital signs and electrocardiograms (ECGs). Any clinically significant lab, vital signs, ECG abnormalities will be captured as an AE.
4. ORR and DCR based on PCWG3-modified (The Prostate Cancer Working Group 3) RECIST v1.1 based endpoints using CT/MRI and bone scans by investigator.
5. PSA50 response is defined as the proportion of participants who have a ≥50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement ≥4 weeks later
6. Derived urine PK parameters from urine PK radioactivity data

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 12

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications